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10 references

1. Bosi A, Laszlo D, Labopin M, Reffeirs J, Michallet M, Gluckman E, et al. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001;19(16):3675-84. 2. Bishop MR, Steinberg SM, Gress RE, Hardy NM, Marchigiani D, Kasten-Sportes C, et al. Targeted pretransplant host lymphocyte depletion prior to T-cell depleted reduced-intensity allogeneic stem cell transplantation. British journal of haematology. 2004;126(6):837-43. 3. Hardy NM, Hakim F, Steinberg SM, Krumlauf M, Cvitkovic R, Babb R, et al. Host T cells affect donor T cell engraftment and graft-versus-host disease after reduced-intensity hematopoietic stem cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2007;13(9):1022-30. 4. Conrad R, Remberger M, Cederlund K, Ringden O, Barkholt L. A comparison between low intensity and reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation for solid tumors. Haematologica. 2008;93(2):265-72. 5. Carvallo C, Childs R. Nonmyeloablative stem cell transplantation as immunotherapy for kidney cancer and other metastatic solid tumors. Cytotechnology. 2003;41(2-3):197-206. 6. Demirer T, Barkholt L, Blaise D, Pedrazzoli P, Aglietta M, Carella AM, et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Clin Pract Oncol. 2008;5(5):256-67. 7. Verneris MR, Wagner JE. Recent developments in cell-based immune therapy for neuroblastoma. Journal of neuroimmune pharmacology. 2007;2(2):134-9. 8. Ladenstein R, Lasset C, Hartmann O, Klingebiel T, Bouffet E, Gadner H, et al. Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation. Bone marrow transplantation. 1994;14(1):37-46. 9. Kanold J, Paillard C, Tchirkov A, Merlin E, Marabelle A, Lutz P, et al. Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant. 2008;42 Suppl 2:S25-30. 10. Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, et al.  
Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haploidentical bone marrow transplantation. Bone marrow transplantation. 2003;32(1):103-6. 11. Hirayama M, Azuma E, Araki M, Komada Y, Nakagawa A. Evidence of graft-versustumor effect in refractory metastatic neuroblastoma. Transplantation. 2006;82(1):142-4.  
12. Lucas K, Schwartz C, Kaplan J. Allogeneic stem cell transplantation in a patient with relapsed Ewing sarcoma. Pediatric blood & cancer. 2008;51(1):142-4. 13. Capitini CM, Derdak J, Hughes MS, Love CP, Baird K, Mackall CL, et al. Unusual sites of extraskeletal metastases of Ewing sarcoma after allogeneic hematopoietic stem cell transplantation. J Pediatr Hematol Oncol. 2009;31(2):142-4. 14. Bregni M, Bernardi M, Ciceri F, Peccatori J. Allogeneic stem cell transplantation for the treatment of advanced solid tumors. Springer Seminars in Immunopathology. 2004;26(1-2):95108. 15. Burdach S, van Kaick B, Laws HJ, Ahrens S, Haase R, Korholz D, et al. Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors: An update after long-term follow-up from two centers of the European Intergroup Study EICESS. Ann Oncol. 2000;11(11):1451-62. 16. Koscielniak E, Gross-Wieltsch U, Treuner J, Winkler P, Klingebiel T, Lang P, et al. Graft-Versus-Ewing Sarcoma Effect and Long-Term Remission Induced by Haploidentical Stem-Cell Transplantation in a Patient With Relapse of Metastatic Disease. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(1):242-4. 17. Doelken R, Weigel S, Schueler F, Doelken G, Beck JF. Poor outcome of two children with relapsed state stage IV alveolar rhabdomyosarcoma after allogeneic stem cell transplantation. Pediatric hematology and oncology. 2005;22(8):699-703. 18. Misawa A, Hosoi H, Tsuchiya K, Iehara T, Sawada T, Sugimoto T. Regression of refractory rhabdomyosarcoma after allogeneic stem-cell transplantation. Pediatric hematology and oncology. 2003;20(2):151-5. 19. Donker AE, Hoogerbrugge PM, Mavinkurve-Groothuis AMC, van de Kar NCAJ, Boetes C, Hulsbergen-van de Kaa CA, et al. Metastatic rhabdomyosarcoma cured after chemotherapy and allogeneic SCT. Bone marrow transplantation. 2009;43(2):179-80. 20. Matthay KK, Seeger RC, Reynolds CP, Stram DO, O'Leary MC, Harris RE, et al. Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the Childrens Cancer Group. Journal of clinical oncology. 1994;12(11):2382-9. 21. Shen BJ, Hou HS, Zhang HQ, Sui XW. Unrelated, HLA-mismatched multiple human umbilical cord blood transfusion in four cases with advanced solid tumors: initial studies. Blood cells. 1994;20(2-3):285-92. 22. Lang P, Pfeiffer M, Müller I, Schumm M, Ebinger M, Koscielniak E, et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klinische Pädiatrie. 2006;218(6):321-6. 23. Dean RM, Fowler DH, Wilson WH, Odom J, Steinberg SM, Chow C, et al. Efficacy of reduced-intensity allogeneic stem cell transplantation in chemotherapy-refractory non-hodgkin lymphoma. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2005;11(8):593-9. 24. Bishop MR, Hou JW, Wilson WH, Steinberg SM, Odom J, Castro K, et al. Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2003;9(3):162-9. 25. Fowler D, Hou J, Foley J, Hakim F, Odom J, Castro K, et al. Phase I clinical trial of donor T-helper type-2 cells after immunoablative, reduced intensity allogeneic PBSC transplant. Cytotherapy. 2002;4(5):429-30. 26. Chamberlain MC, Prados MD, Silver P, Levin VA. A phase II trial of oral melphalan in recurrent primary brain tumors. Am J Clin Oncol. 1988;11(1):52-4. 27. Appelbaum FR, Buckner CD. Overview of the clinical relevance of autologous bone marrow transplantation. Clin Haematol. 1986;15(1):1-18.  
28. Gonzalez-Llano O, Jaime-Perez J, Cantu-Rodriguez O, Mancias-Guerra C, GutierrezAguirre H, Herrera-Garza J, et al. Successful father-to-son stem cell transplantation in a child with hemophagocytic lymphohistiocytosis using a reduced-intensity conditioning regimen. Eur J Haematol. 2006;77(4):341-4. 29. Llano OG, Perez JC, Rodriguez OC, Guerra CM, Aguirre HG, Garza JL, et al. Allogeneic hematopoietic stem cell transplantation using a reduced-intensity conditioning regimen in infants: experience at a single institution in Mexico. Pediatr Hematol Oncol. 2008;25(1):39-47. 30. Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: an evidence-based review. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2005;11(11):823-61. 31. Miser JS, Goldsby RE, Chen Z, Krailo MD, Tarbell NJ, Link MP, et al. Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy--a report from the Children's Oncology Group. Pediatric blood & cancer. 2007;49(7):894-900. 32. Paulussen M, Ahrens S, Burdach S, Craft A, Dockhorn-Dworniczak B, Dunst J, et al. Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. European Intergroup Cooperative Ewing Sarcoma Studies. Ann Oncol. 1998;9(3):27581. 33. Pinkerton CR, Bataillard A, Guillo S, Oberlin O, Fervers B, Philip T. Treatment strategies for metastatic Ewing's sarcoma. Eur J Cancer. 2001;37(11):1338-44. 34. Institute NC. PDQ Summary. http://wwwcancergov/cancertopics. 2009. 35. Hayes-Jordan A, Doherty DK, West SD, Raney RB, Blakely ML, Cox CS, Jr., et al.  
Outcome after surgical resection of recurrent rhabdomyosarcoma. J Pediatr Surg.  
2006;41(4):633-8; discussion -8. 36. Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP. Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg. 2005;40(1):251-5. 37. Gray JC, Kohler JA. Immunotherapy for neuroblastoma: turning promise into reality. Pediatric blood & cancer. 2009;53(6):931-40. 38. Cotterill SJ, Pearson AD, Pritchard J, Kohler JA, Foot AB. Late relapse and prognosis for neuroblastoma patients surviving 5 years or more: a report from the European Neuroblastoma Study Group "Survey". Medical and pediatric oncology. 2001;36(1):235-8. 39. Mertens AC, Yasui Y, Neglia JP, Potter JD, Nesbit ME, Jr., Ruccione K, et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001;19(13):3163-72. 40. Navid F, Armstrong M, Barfield RC. Immune therapies for neuroblastoma. Cancer Biol Ther. 2009;8(10):874-82. 41. Castel V, Canete A, Melero C, Acha T, Navajas A, Garcia-Miguel P, et al. Results of the cooperative protocol (N-III-95) for metastatic relapses and refractory neuroblastoma. Medical and pediatric oncology. 2000;35(6):724-6. 42. Creutzig U, Ritter J, Zimmermann M, Reinhardt D, Hermann J, Berthold F, et al. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Munster 93. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001;19(10):2705-13. 43. Stevens RF, Hann IM, Wheatley K, Gray RG. Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council's 10th AML trial. MRC Childhood Leukaemia Working Party. British journal of haematology. 1998;101(1):130-40. 44. Perel Y, Auvrignon A, Leblanc T, Vannier JP, Michel G, Nelken B, et al. Impact of addition of maintenance therapy to intensive induction and consolidation chemotherapy for childhood acute myeloblastic leukemia: results of a prospective randomized trial, LAME 89/91. Leucamie Aique Myeloide Enfant. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002;20(12):2774-82. 45. Capizzi RL, Poole M, Cooper MR, Richards F, 2nd, Stuart JJ, Jackson DV, Jr., et al. Treatment of poor risk acute leukemia with sequential high-dose ARA-C and asparaginase. Blood. 1984;63(3):694-700. 46. Woods WG, Neudorf S, Gold S, Sanders J, Buckley JD, Barnard DR, et al. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood. 2001;97(1):56-62. 47. Feig SA, Lampkin B, Nesbit ME, Woods WG, Versteeg CM, Buckley JD, et al. Outcome of BMT during first complete remission of AML: a comparison of two sequential studies by the Children's Cancer Group. Bone Marrow Transplant. 1993;12(1):65-71. 48. Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. UK Medical Research Council Adult and Children's Leukaemia Working Parties. Lancet (London, England). 1998;351(9104):700-8. 49. Razzouk BI, Estey E, Pounds S, Lensing S, Pierce S, Brandt M, et al. Impact of age on outcome of pediatric acute myeloid leukemia: a report from 2 institutions. Cancer. 2006;106(11):2495-502. 50. Ortega JJ, Madero L, Martin G, Verdeguer A, Garcia P, Parody R, et al. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(30):7632-40.  
51. Testi AM, Biondi A, Lo Coco F, Moleti ML, Giona F, Vignetti M, et al. GIMEMAAIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia
(APL) in children. Blood. 2005;106(2):447-53. 52. De Botton S, Chevret S, Sanz M, Dombret H, Thomas X, Guerci A, et al. Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial. British journal of haematology. 2000;111(3):801-6. 53. Fenaux P, Chevret S, Guerci A, Fegueux N, Dombret H, Thomas X, et al. Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. European APL group. Leukemia. 2000;14(8):1371-7. 54. Ravindranath Y, Abella E, Krischer JP, Wiley J, Inoue S, Harris M, et al. Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. Blood. 1992;80(9):2210-4. 55. Gamis AS, Woods WG, Alonzo TA, Buxton A, Lange B, Barnard DR, et al. Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children's Cancer Group Study 2891. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003;21(18):3415-22. 56. Massey GV. Transient leukemia in newborns with Down syndrome. Pediatric blood & cancer. 2005;44(1):29-32. 57. Oliansky DM, Rizzo JD, Aplan PD, Arceci RJ, Leone L, Ravindranath Y, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2007;13(1):1-25. 58. Amadori S, Testi AM, Arico M, Comelli A, Giuliano M, Madon E, et al. Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1993;11(6):1046-54. 59. Dahl GV, Kalwinsky DK, Mirro J, Jr., Look AT, Pui CH, Murphy SB, et al. Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1990;8(2):295-303. 60. Nesbit ME, Jr., Buckley JD, Feig SA, Anderson JR, Lampkin B, Bernstein ID, et al. Chemotherapy for induction of remission of childhood acute myeloid leukemia followed by marrow transplantation or multiagent chemotherapy: a report from the Childrens Cancer Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994;12(1):127-35. 61. Wells RJ, Woods WG, Buckley JD, Odom LF, Benjamin D, Bernstein I, et al. Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Childrens Cancer Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994;12(11):2367-77. 62. Aladjidi N, Auvrignon A, Leblanc T, Perel Y, Benard A, Bordigoni P, et al. Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003;21(23):4377-85. 63. Watson M, Buck G, Wheatley K, Homewood JR, Goldstone AH, Rees JK, et al. Adverse impact of bone marrow transplantation on quality of life in acute myeloid leukaemia patients; analysis of the UK Medical Research Council AML 10 Trial. Eur J Cancer. 2004;40(7):971-8. 64. Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. The New England journal of medicine. 1998;339(23):1649-56. 65. Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. The New England journal of medicine. 1995;332(4):217-23. 66. Burnett AK, Wheatley K, Goldstone AH, Stevens RF, Hann IM, Rees JH, et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. British journal of haematology. 2002;118(2):385-400. 67. Chen AR, Alonzo TA, Woods WG, Arceci RJ. Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation?--an American view. British journal of haematology. 2002;118(2):378-84. 68. Creutzig U, Reinhardt D. Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation?--a European view. British journal of haematology. 2002;118(2):365-77. 69. Smith FO, Alonzo TA, Gerbing RB, Woods WG, Arceci RJ. Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891. Leukemia. 2005;19(12):2054-62. 70. Ravindranath Y, Chang M, Steuber CP, Becton D, Dahl G, Civin C, et al. Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia. 2005;19(12):2101-16. 71. Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1996;14(1):18-24. 72. McLean TW, Ringold S, Neuberg D, Stegmaier K, Tantravahi R, Ritz J, et al. TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. Blood. 1996;88(11):4252-8. 73. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, et al. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster Study Group. Blood. 1997;90(2):571-7. 74. Uckun FM, Pallisgaard N, Hokland P, Navara C, Narla R, Gaynon PS, et al. Expression of TEL-AML1 fusion transcripts and response to induction therapy in standard risk acute lymphoblastic leukemia. Leukemia & lymphoma. 2001;42(1-2):41-56. 75. Kanerva J, Saarinen-Pihkala UM, Niini T, Riikonen P, Mottonen M, Makipernaa A, et al. Favorable outcome in 20-year follow-up of children with very-low-risk ALL and minimal standard therapy, with special reference to TEL-AML1 fusion. Pediatric blood & cancer. 2004;42(1):30-5. 76. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, et al. Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants. Leukemia. 1998;12(5):779-87. 77. Pui CH, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, et al. Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. Blood. 1991;77(3):440-7. 78. Crist W, Pullen J, Boyett J, Falletta J, van Eys J, Borowitz M, et al. Clinical and biologic features predict a poor prognosis in acute lymphoid leukemias in infants: a Pediatric Oncology Group Study. Blood. 1986;67(1):135-40. 79. Reaman G, Zeltzer P, Bleyer WA, Amendola B, Level C, Sather H, et al. Acute lymphoblastic leukemia in infants less than one year of age: a cumulative experience of the Children's Cancer Study Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1985;3(11):1513-21. 80. Arico M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A, et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. The New England journal of medicine. 2000;342(14):998-1006. 81. Crist WM, Carroll AJ, Shuster JJ, Behm FG, Whitehead M, Vietti TJ, et al. Poor prognosis of children with pre-B acute lymphoblastic leukemia is associated with the t(1;19)(q23;p13): a Pediatric Oncology Group study. Blood. 1990;76(1):117-22. 82. Uckun FM, Sensel MG, Sather HN, Gaynon PS, Arthur DC, Lange BJ, et al. Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1998;16(2):527-35. 83. Moorman AV, Richards SM, Martineau M, Cheung KL, Robinson HM, Jalali GR, et al. Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia. Blood. 2003;102(8):2756-62. 84. Charrin C, Thomas X, Ffrench M, Le QH, Andrieux J, Mozziconacci MJ, et al. A report from the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL). Blood. 2004;104(8):2444-51. 85. Heerema NA, Sather HN, Sensel MG, Zhang T, Hutchinson RJ, Nachman JB, et al. Prognostic impact of trisomies of chromosomes 10, 17, and 5 among children with acute lymphoblastic leukemia and high hyperdiploidy (> 50 chromosomes). Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(9):1876-87. 86. Sutcliffe MJ, Shuster JJ, Sather HN, Camitta BM, Pullen J, Schultz KR, et al. High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children's Oncology Group (COG) initiative. Leukemia. 2005;19(5):734-40. 87. Harrison CJ, Moorman AV, Broadfield ZJ, Cheung KL, Harris RL, Reza Jalali G, et al. Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia. British journal of haematology. 2004;125(5):552-9. 88. Heerema NA, Nachman JB, Sather HN, Sensel MG, Lee MK, Hutchinson R, et al. Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children's cancer group. Blood. 1999;94(12):4036-45. 89. Raimondi SC, Zhou Y, Mathew S, Shurtleff SA, Sandlund JT, Rivera GK, et al. Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia. Cancer. 2003;98(12):2715-22. 90. Pui CH, Carroll AJ, Raimondi SC, Land VJ, Crist WM, Shuster JJ, et al. Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line. Blood. 1990;75(5):1170-7. 91. Chessells JM. Relapsed lymphoblastic leukaemia in children: a continuing challenge. British journal of haematology. 1998;102(2):423-38. 92. Gaynon PS, Harris RE, Altman AJ, Bostrom BC, Breneman JC, Hawks R, et al. Bone marrow transplantation versus prolonged intensive chemotherapy for children with acute lymphoblastic leukemia and an initial bone marrow relapse within 12 months of the completion of primary therapy: Children's Oncology Group study CCG-1941. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006;24(19):3150-6. 93. Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(24):3971-8. 94. Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-50. 95. Ritchey AK, Pollock BH, Lauer SJ, Andejeski Y, Barredo J, Buchanan GR. Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999;17(12):3745-52. 96. Buchanan GR, Boyett JM, Pollock BH, Smith SD, Yanofsky RA, Ghim T, et al. Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study. Cancer. 1991;68(1):48-55. 97. Barrett AJ, Horowitz MM, Pollock BH, Zhang MJ, Bortin MM, Buchanan GR, et al. Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. The New England journal of medicine. 1994;331(19):1253-8. 98. Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet (London, England). 2005;366(9486):635-42. 99. Sadowitz PD, Smith SD, Shuster J, Wharam MD, Buchanan GR, Rivera GK. Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood. 1993;81(3):602-9. 100. Ravandi F, Kebriaei P. Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2009;23(5):1043-63, vi.  
101. Pulsipher MA. Treatment of CML in pediatric patients: should imatinib mesylate (STI571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy? Pediatric blood
& cancer. 2004;43(5):523-33.  
102. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Fiveyear follow-up of patients receiving imatinib for chronic myeloid leukemia. The New England journal of medicine. 2006;355(23):2408-17. 103. Shah NP. Loss of response to imatinib: mechanisms and management. Hematology Am Soc Hematol Educ Program. 2005:183-7. 104. Kolb EA, Pan Q, Ladanyi M, Steinherz PG. Imatinib mesylate in Philadelphia chromosome-positive leukemia of childhood. Cancer. 2003;98(12):2643-50. 105. Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, et al. Allogeneic hematopoietic stem cell transplantation (alloSCT) for chronic myeloid leukemia in the imatinib era; evaluation of its impact within a subgroup of the randomized German CML
Study IV. Blood. 2009. 106. Goldman JM, Marin D. Management decisions in chronic myeloid leukemia. Semin Hematol. 2003;40(1):97-103. 107. Wassmann B, Pfeifer H, Scheuring U, Klein SA, Gokbuget N, Binckebanck A, et al. Therapy with imatinib mesylate (Glivec) preceding allogeneic stem cell transplantation (SCT) in relapsed or refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Leukemia. 2002;16(12):2358-65. 108. Weisdorf DJ, Anasetti C, Antin JH, Kernan NA, Kollman C, Snyder D, et al. Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation. Blood. 2002;99(6):1971-7. 109. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet (London, England). 1998;352(9134):1087-92. 110. Silver RT, Woolf SH, Hehlmann R, Appelbaum FR, Anderson J, Bennett C, et al. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology. Blood. 1999;94(5):1517-36. 111. Stary J, Locatelli F, Niemeyer CM. Stem cell transplantation for aplastic anemia and myelodysplastic syndrome. Bone Marrow Transplant. 2005;35 Suppl 1:S13-6. 112. Niemeyer CM, Kratz CP, Hasle H. Pediatric myelodysplastic syndromes. Curr Treat Options Oncol. 2005;6(3):209-14. 113. Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17(2):277-82. 114. Mandel K, Dror Y, Poon A, Freedman MH. A practical, comprehensive classification for pediatric myelodysplastic syndromes: the CCC system. J Pediatr Hematol Oncol. 2002;24(7):596-605. 115. Occhipinti E, Correa H, Yu L, Craver R. Comparison of two new classifications for pediatric myelodysplastic and myeloproliferative disorders. Pediatric blood & cancer. 2005;44(3):240-4. 116. Hasle H, Clemmensen IH, Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet (London, England). 2000;355(9199):165-9. 117. Niemeyer CM, Arico M, Basso G, Biondi A, Cantu Rajnoldi A, Creutzig U, et al. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS). Blood. 1997;89(10):3534-43. 118. Hasle H, Arico M, Basso G, Biondi A, Cantu Rajnoldi A, Creutzig U, et al. Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS). Leukemia. 1999;13(3):376-85. 119. Woods WG, Barnard DR, Alonzo TA, Buckley JD, Kobrinsky N, Arthur DC, et al. Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children's Cancer Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002;20(2):434-40. 120. Freedman MH, Estrov Z, Chan HS. Juvenile chronic myelogenous leukemia. Am J Pediatr Hematol Oncol. 1988;10(3):261-7. 121. Yoshimi A, Bader P, Matthes-Martin S, Stary J, Sedlacek P, Duffner U, et al. Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia. Leukemia. 2005;19(6):971-7. 122. Creutzig U, Bender-Gotze C, Ritter J, Zimmermann M, Stollmann-Gibbels B, Korholz D, et al. The role of intensive AML-specific therapy in treatment of children with RAEB and RAEB-t. Leukemia. 1998;12(5):652-9. 123. Locatelli F, Nollke P, Zecca M, Korthof E, Lanino E, Peters C, et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood. 2005;105(1):410-9. 124. Arico M, Biondi A, Pui CH. Juvenile myelomonocytic leukemia. Blood. 1997;90(2):47988. 125. Bunin N, Saunders F, Leahey A, Doyle J, Calderwood S, Freedman MH. Alternative donor bone marrow transplantation for children with juvenile myelomonocytic leukemia. J Pediatr Hematol Oncol. 1999;21(6):479-85. 126. Smith FO, King R, Nelson G, Wagner JE, Robertson KA, Sanders JE, et al. Unrelated donor bone marrow transplantation for children with juvenile myelomonocytic leukaemia. British journal of haematology. 2002;116(3):716-24. 127. Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, et al. A 2step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001;97(3):616-23. 128. Schellong G, Dorffel W, Claviez A, Korholz D, Mann G, Scheel-Walter HG, et al. Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(25):6181-9. 129. Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, et al. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002;20(18):3765-71. 130. Aparicio J, Segura A, Garcera S, Oltra A, Santaballa A, Yuste A, et al. ESHAP is an active regimen for relapsing Hodgkin's disease. Ann Oncol. 1999;10(5):593-5. 131. Bonfante V, Viviani S, Santoro A, Devizzi L, Di Russo A, Zanini M, et al. Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease. British journal of haematology. 1998;103(2):533-5. 132. Zinzani PL, Bendandi M, Stefoni V, Albertini P, Gherlinzoni F, Tani M, et al. Value of gemcitabine treatment in heavily pretreated Hodgkin's disease patients. Haematologica. 2000;85(9):926-9. 133. Santoro A, Bredenfeld H, Devizzi L, Tesch H, Bonfante V, Viviani S, et al. Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(13):2615-9. 134. Peniket AJ, Ruiz de Elvira MC, Taghipour G, Cordonnier C, Gluckman E, de Witte T, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant. 2003;31(8):667-78. 135. Lieskovsky YE, Donaldson SS, Torres MA, Wong RM, Amylon MD, Link MP, et al. High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin's disease: results and prognostic indices. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;22(22):4532-40. 136. Akhtar S, Weshi AE, Rahal M, Khafaga Y, Tbakhi A, Humaidan H, et al. Factors affecting autologous peripheral blood stem cell collection in patients with relapsed or refractory diffuse large cell lymphoma and Hodgkin lymphoma: a single institution result of 168 patients. Leukemia & lymphoma. 2008;49(4):769-78. 137. Cooney JP, Stiff PJ, Toor AA, Parthasarathy M. BEAM allogeneic transplantation for patients with Hodgkin's disease who relapse after autologous transplantation is safe and effective. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2003;9(3):177-82. 138. Claviez A, Klingebiel T, Beyer J, Nurnberger W, Ehninger G, Suttorp M, et al. Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin's disease. Ann Hematol. 2004;83(4):237-41. 139. Sureda A, Schmitz N. Role of allogeneic stem cell transplantation in relapsed or refractory Hodgkin's disease. Ann Oncol. 2002;13 Suppl 1:128-32. 140. Attarbaschi A, Dworzak M, Steiner M, Urban C, Fink FM, Reiter A, et al. Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: a population-based analysis of the Austrian Cooperative Study Group. Pediatric blood & cancer. 2005;44(1):70-6. 141. Kobrinsky NL, Sposto R, Shah NR, Anderson JR, DeLaat C, Morse M, et al. Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001;19(9):2390-6. 142. Attias D, Weitzman S. The efficacy of rituximab in high-grade pediatric B-cell lymphoma/leukemia: a review of available evidence. Curr Opin Pediatr. 2008;20(1):17-22. 143. Saarinen-Pihkala UM, Gustafsson G, Ringden O, Heilmann C, Glomstein A, Lonnerholm G, et al. No disadvantage in outcome of using matched unrelated donors as compared with matched sibling donors for bone marrow transplantation in children with acute lymphoblastic leukemia in second remission. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001;19(14):3406-14. 144. Giebel S, Giorgiani G, Martinetti M, Zecca M, Maccario R, Salvaneschi L, et al. Low incidence of severe acute graft-versus-host disease in children given haematopoietic stem cell transplantation from unrelated donors prospectively matched for HLA class I and II alleles with high-resolution molecular typing. Bone Marrow Transplant. 2003;31(11):987-93. 145. Talano JA, Margolis DA. Recent molecular and cellular advances in pediatric bone marrow transplantation. Pediatr Clin North Am. 2006;53(4):685-98. 146. Balduzzi A, Gooley T, Anasetti C, Sanders JE, Martin PJ, Petersdorf EW, et al. Unrelated donor marrow transplantation in children. Blood. 1995;86(8):3247-56. 147. Davies SM, Wagner JE, Defor T, Blazar BR, Katsanis E, Kersey JH, et al. Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia. British journal of haematology. 1997;96(4):749-56. 148. Davies SM, Wagner JE, Shu XO, Blazar BR, Katsanis E, Orchard PJ, et al. Unrelated donor bone marrow transplantation for children with acute leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1997;15(2):557-65. 149. Bunin N, Carston M, Wall D, Adams R, Casper J, Kamani N, et al. Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood. 2002;99(9):3151-7. 150. Woolfrey AE, Anasetti C, Storer B, Doney K, Milner LA, Sievers EL, et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood. 2002;99(6):2002-8. 151. Talano JM, Casper JT, Camitta BM, Keever-Taylor CA, Murray KJ, Eapen M, et al. Alternative donor bone marrow transplant for children with Philadelphia chromosome ALL. Bone Marrow Transplant. 2006;37(2):135-41. 152. Duggan P, Booth K, Chaudhry A, Stewart D, Ruether JD, Gluck S, et al. Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis. Bone Marrow Transplant. 2002;30(10):681-6. 153. Munoz A, Diaz-Heredia C, Diaz MA, Badell I, Verdeguer A, Martinez A, et al. Allogeneic hemopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission-similar outcomes after matched related and unrelated donor transplant: a study of the Spanish Working Party for Blood and Marrow Transplantation in Children (Getmon). Pediatr Hematol Oncol. 2008;25(4):245-59. 154. Uzunel M, Remberger M, Sairafi D, Hassan Z, Mattsson J, Omazic B, et al. Unrelated versus related allogeneic stem cell transplantation after reduced intensity conditioning. Transplantation. 2006;82(7):913-9. 155. Giebel S, Locatelli F, Lamparelli T, Velardi A, Davies S, Frumento G, et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood. 2003;102(3):814-9. 156. Maury S, Balere-Appert ML, Chir Z, Boiron JM, Galambrun C, Yakouben K, et al. Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica. 2007;92(5):589-96.  
157. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. Highresolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110(13):4576-83. 158. Loiseau P, Busson M, Balere ML, Dormoy A, Bignon JD, Gagne K, et al. HLA Association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2007;13(8):965-74. 159. Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood. 2012;119(17):3908-16. 160. Finke J, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, et al. Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2012;18(11):1716-26. 161. Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. The New England journal of medicine. 1993;328(9):593-602. 162. Champlin RE, Schmitz N, Horowitz MM, Chapuis B, Chopra R, Cornelissen JJ, et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2000;95(12):3702-9. 163. Papadopoulos EB, Carabasi MH, Castro-Malaspina H, Childs BH, Mackinnon S, Boulad F, et al. T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood. 1998;91(3):1083-90. 164. Montero A, Savani BN, Shenoy A, Read EJ, Carter CS, Leitman SF, et al. T-cell depleted peripheral blood stem cell allotransplantation with T-cell add-back for patients with hematological malignancies: effect of chronic GVHD on outcome. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2006;12(12):1318-25. 165. Cornelissen JJ, Lowenberg B. Developments in T-cell depletion of allogeneic stem cell grafts. Curr Opin Hematol. 2000;7(6):348-52. 166. Ottinger HD, Beelen DW, Scheulen B, Schaefer UW, Grosse-Wilde H. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. Blood. 1996;88(7):2775-9. 167. Storek J, Witherspoon RP, Maloney DG, Chauncey TR, Storb R. Improved reconstitution of CD4 T cells and B cells but worsened reconstitution of serum IgG levels after allogeneic transplantation of blood stem cells instead of marrow. Blood. 1997;89(10):3891-3. 168. Martinez C, Urbano-Ispizua A, Rozman C, Marin P, Rovira M, Sierra J, et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol. 1999;27(3):561-8. 169. Behringer D, Bertz H, Schmoor C, Berger C, Dwenger A, Finke J. Quantitative lymphocyte subset reconstitution after allogeneic hematopoietic transplantation from matched related donors with CD34+ selected PBPC grafts unselected PBPC grafts or BM grafts. Bone Marrow Transplant. 1999;24(3):295-302. 170. Chen X, Hale GA, Barfield R, Benaim E, Leung WH, Knowles J, et al. Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies. British journal of haematology. 2006;135(4):524-32. 171. Bethge WA, Faul C, Bornhäuser M, Stuhler G, Beelen DW, Lang P, et al. Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. Blood cells, molecules & diseases. 2008;40(1):13-9. 172. Novitzky N, Thomas V, du Toit C, McDonald A. Reduced-intensity conditioning for severe aplasia using fludarabine and CY followed by infusion of ex vivo T-cell-depleted grafts leads to excellent engraftment and absence of GVHD. Bone Marrow Transplant. 2009;43(10):779-85. 173. Chaudhury S, Auerbach A, Kernan N, Small T, Prockop S, Scaradavou A, et al. Fludarabine-based cytoreductive regimen and T-cell-depleted grafts from alternative donors for the treatment of high-risk patients with Fanconi anaemia. British journal of haematology. 2008;140(6):644-55. 174. Lang P, Handgretinger R. Haploidentical SCT in children: an update and future perspectives. Bone Marrow Transplant. 2008;42(S2):S54-S9. 175. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C, et al. Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood. 1994;84(11):3948-55. 176. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, et al. Treatment of High-Risk Acute Leukemia with T-Cell-Depleted Stem Cells from Related Donors with One Fully Mismatched HLA Haplotype. The New England journal of medicine. 1998;339(17):118693. 177. Aversa F, Terenzi A, Felicini R, Tabilio A, Falzetti F, Carotti A, et al. Mismatched T cell-depleted hematopoietic stem cell transplantation for children with high-risk acute leukemia. Bone Marrow Transplant. 1998;22 Suppl(5):S29-32.  
178. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, et al. Full HaplotypeMismatched Hematopoietic Stem-Cell Transplantation: A Phase II Study in Patients With Acute Leukemia at High Risk of Relapse. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(15):3447-54. 179. Elhasid R, Arush MB, Zaidman I, Leiba R, Barak AB, Postovsky S, et al. Safe and Efficacious Allogeneic Bone Marrow Transplantation for Nonmalignant Disorders Using Partial T Cell Depletion and No Posttransplantation Graft-Versus-Host-Disease Prophylaxis. Biology of Blood and Marrow Transplantation. 2007;13(3):329-38. 180. Castriconi R, Dondero A, Corrias MV, Lanino E, Pende D, Moretta L, et al. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer research. 2004;64(24):9180-4. 181. Prigione I, Corrias M, Airoldi I, Raffaghello L, Morandi F, Bocca P, et al. Immunogenicity of Human Neuroblastoma. Annals of the New York Academy of Sciences. 2004;1028(Signal Transduction and Communication in Cancer Cells):69-80. 182. Chin T, Toy C, Vandeven C, Cairo MS. Lymphokine-activated killer cytotoxicity in neonatal mononuclear cells: in vitro responses to tumor cell lines from pediatric solid tumors. Pediatric research. 1989;25(2):156-60. 183. Klob S, Bochennek K, Huenecke S, Zimmermann S-Y, KuÁi S, M¸ller T, et al. A novel five-colour flow cytometric assay to determine NK cell cytotoxicity against neuroblastoma and other adherent tumour cells. Journal of Immunological Methods. 2007;325(1-2):140-7. 184. Castriconi R, Dondero A, Cilli M, Ognio E, Pezzolo A, De Giovanni B, et al. Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice. Cancer immunology, immunotherapy. 2007;56(11):1733-42. 185. Osenga KL, Hank JA, Albertini MR, Gan J, Sternberg AG, Eickhoff J, et al. A Phase I Clinical Trial of the hu14.18-IL2 (EMD 273063) as a Treatment for Children with Refractory or Recurrent Neuroblastoma and Melanoma: a Study of the Children's Oncology Group. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(6):1750-9. 186. Capitini CM, Cooper LJ, Egeler RM, Handgretinger R, Locatelli F, Sondel PM, et al. Highlights of the First International "Immunotherapy in Pediatric Oncology: Progress and Challenges" Meeting. J Pediatr Hematol Oncol. 2009;31(4):227-44. 187. Verhoeven DHJ, de Hooge ASK, Mooiman ECK, Santos SJ, ten Dam MM, Gelderblom H, et al. NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways. Molecular immunology. 2008;45(15):3917-25. 188. Wu A, Wiesner S, Xiao J, Ericson K, Chen W, Hall W, et al. Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy. Journal of Neuro-Oncology. 2007;83(2):121-31. 189. Multhoff G, Botzler C, Wiesnet M, Eissner G, Issels R. CD3- large granular lymphocytes recognize a heat-inducible immunogenic determinant associated with the 72-kD heat shock protein on human sarcoma cells. Blood. 1995;86(4):1374-82. 190. Nolibé D, Poupon MF. Enhancement of pulmonary metastases induced by decreased lung natural killer cell activity. Journal of the National Cancer Institute. 1986;77(1):99-103. 191. Evans R, Fuller JA, Christianson G, Krupke DM, Troutt AB. IL-15 Mediates Anti-tumor Effects after Cyclophosphamide Injection of Tumor-Bearing Mice and Enhances Adoptive Immunotherapy: The Potential Role of NK Cell Subpopulations. Cellular Immunology. 1997;179(1):66-73. 192. Belova OB, Vinnichuk UD, Shlakhovenko VA, Berezhnaya NM. Efficacy of different immunotherapy approaches toward treatment of doxorubicin-resistant and doxorubicin-sensitive WUDQVSODQWDEOHUKDEGRP\RVDUFRPD(NVSHULPHQWDOމQDLଊD
ଋ onkologiL
ଊD
ଋ. 2007;29(4):272-6.  
193. Bauer M, Reaman GH, Hank JA, Cairo MS, Anderson P, Blazar BR, et al. A phase II trial of human recombinant interleukin-2 administered as a 4-day continuous infusion for children with refractory neuroblastoma, non-Hodgkin's lymphoma, sarcoma, renal cell carcinoma, and malignant melanoma. A Childrens Cancer Group study. Cancer. 1995;75(12):2959-65.  
194. Pende D, Marcenaro S, Falco M, Martini S, Bernardo ME, Montagna D, et al. Antileukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and re-definition of inhibitory KIR specificity. Blood. 2008:blood-2008-06-164103.  
195. Boyiadzis M, Memon S, Carson J, Allen K, Szczepanski MJ, Vance BA, et al. Upregulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2008;14(3):290-300. 196. Murphy WJ, Keller JR, Harrison CL, Young HA, Longo DL. Interleukin-2-activated natural killer cells can support hematopoiesis in vitro and promote marrow engraftment in vivo. Blood. 1992;80(3):670-7. 197. Gewirtz AM, Xu WY, Mangan KF. Role of natural killer cells, in comparison with T lymphocytes and monocytes, in the regulation of normal human megakaryocytopoiesis in vitro. Journal of immunology (Baltimore, Md : 1950). 1987;139(9):2915-24. 198. Murphy WJ, Longo DL. Hematopoietic growth-promoting effects of natural killer cells in mice in response to in vivo administration of human interleukin-2. J Natl Cancer Inst. 1992;84(15):1195-200. 199. Murphy WJ, Raziuddin A, Mason L, Kumar V, Bennett M, Longo DL. NK cell subsets in the regulation of murine hematopoiesis. I. 5E6+ NK cells promote hematopoietic growth in H-2d strain mice. Journal of immunology (Baltimore, Md : 1950). 1995;155(6):2911-7. 200. Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105(12):4878-84. 201. Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051-7. 202. Passweg JR, Stern M, Koehl U, Uharek L, Tichelli A. Use of natural killer cells in hematopoetic stem cell transplantation. Bone Marrow Transplant. 2005;35(7):637-43. 203. Passweg JR, Tichelli A, Meyer-Monard S, Heim D, Stern M, Kuhne T, et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004;18(11):1835-8. 204. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science (New York, NY). 2002;295(5562):2097-100. 205. Murphy W, Koh C, Raziuddin A, Bennett M, Longo D. Immunobiology of natural killer cells and bone marrow transplantation: merging of basic and preclinical studies. Immunological reviews. 2001;181(1):279-89. 206. Asai O, Longo DL, Tian ZG, Hornung RL, Taub DD, Ruscetti FW, et al. Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation. The Journal of clinical investigation. 1998;101(9):1835-42. 207. Lang P. Co-Transfusion of Donor NK Cells in Haploidentical Stem Cell Transplantation. Blood. 2008;112(ASH Annual Meeting Abstracts ):Abstract 2907. 208. Rizzieri D. Safety Trial of NK Cell Enhanced Donor Lymphocyte Infusions from a 3-5/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation. Blood. 2008;112(ASH Annual Meeting Abstracts):Abstract 342. 209. Siegler U, Kalberer CP, Nowbakht P, Sendelov S, Meyer-Monard S, Wodnar-Filipowicz A. Activated natural killer cells from patients with acute myeloid leukemia are cytotoxic against autologous leukemic blasts in NOD//SCID mice. Leukemia. 2005;19(12):2215-22.  
210. Isgro A. Donor's NK Cells May Influence the Engraftment in Pediatrics Patients after TCell Depleted Haploidentical Stem Cell Transplant for Thalassemia. Blood. 2008;112(ASH
Annual Meeting Abstracts):Abstract 4595. 211. Imai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005;106(1):376-83. 212. Sanders JE, Thomas ED, Buckner CD, Doney K. Marrow transplantation for children with acute lymphoblastic leukemia in second remission. Blood. 1987;70(1):324-6. 213. Wiener LS, Steffen-Smith E, Fry T, Wayne AS. Hematopoietic stem cell donation in children: a review of the sibling donor experience. J Psychosoc Oncol. 2007;25(1):45-66.  
| 70% Both greater restriction of, and less  time spent in, play activities.                                                                      | 60% Up and around, but minimal active  play; keeps busy with quieter  activities.                                                  | 50% Gets dressed, but lies around much  of the day; no active play; able to  participate in quiet play and  activities.   | Mostly in bed; participates in quiet  activities.                                                                                                |
|-------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------|
| 90% Minor restrictions in physically  strenuous activity.                                                                                       | 80% Active, but tires more quickly.                                                                                                |                                                                                                                           |                                                                                                                                                  |
| 100% Fully active, normal.                                                                                                                      |                                                                                                                                    |                                                                                                                           |                                                                                                                                                  |
| Score Description                                                                                                                               |                                                                                                                                    |                                                                                                                           |                                                                                                                                                  |
| Lansky                                                                                                                                          | 40%                                                                                                                                |                                                                                                                           |                                                                                                                                                  |
| 90% Able to carry on normal activity;  minor sighs of symptoms of  disease.                                                                     | 70% Cares for self, unable to carry on  normal activity or do active  work.                                                        | 50% Requires considerable assistance  and frequent medical care.                                                          |                                                                                                                                                  |
| 80% Able to carry on normal activity  with effort; some signs or  symptoms of disease.                                                          | 60% Requires occasional assistance  but is able to care for most of                                                                | own needs.                                                                                                                | 40% Disabled; requires special care  and assistance.  Capable of only limited self-care, confined to  bed or chair more than 50% of waking hours |
| 100% Normal, no complaints, no  evidence of disease.                                                                                            |                                                                                                                                    |                                                                                                                           |                                                                                                                                                  |
| Score Description                                                                                                                               |                                                                                                                                    |                                                                                                                           |                                                                                                                                                  |
| Karnofsky                                                                                                                                       | Ambulatory and capable of all self-care but  unable to carry out any work activities. Up and  about more than 50% of waking hours. |                                                                                                                           |                                                                                                                                                  |
| 1 Restricted in physically strenuous activity but  ambulatory, able to carry out light or  sedentary work, e.g., light housework, office  work. |                                                                                                                                    |                                                                                                                           |                                                                                                                                                  |
| Fully active, able to carry on all pre-disease  performance without restriction.                                                                |                                                                                                                                    |                                                                                                                           |                                                                                                                                                  |
| Score Description                                                                                                                               | 0                                                                                                                                  | 2                                                                                                                         | 3                                                                                                                                                |  
Version Date: 07/23/201811 APPENDICES11.1 APPENDIX 1: PERFORMANCE STATUS **PERFORMANCE STATUS CRITERIA** *Karnofsky and Lansky performance scores are intended to be multiples of 10*.ECOG (Zubrod)  
| 20% Often sleeping; play entirely limited  to very passive activities.                  |                                                                                  |                                                                                  |                                                  |                    |
|-----------------------------------------------------------------------------------------|----------------------------------------------------------------------------------|----------------------------------------------------------------------------------|--------------------------------------------------|--------------------|
| 30% In bed; needs assistance even for  quiet play.                                      | 10% No play; does not get out of bed                                             | 0% Unresponsive; Dead                                                            |                                                  |                    |
| 118                                                                                     | 30% Severely disabled;  hospitalization indicated,  although death not imminent. | 20% Very ill; hospitalization  necessary; active supportive  treatment required. | 10% Moribund, fatal process  progressing rapidly | 0% Patient expired |
| Completely disabled. Cannot carry on any  self-care. Totally confined to a bed or chair |                                                                                  |                                                                                  |                                                  |                    |
| Abbreviated Title: NK cell therapy Version Date: 07/23/2018                             | 5 Dead                                                                           |                                                                                  |                                                  |                    |
| 4                                                                                       |                                                                                  |                                                                                  |                                                  |                    |  
| OffTreatme nt                                                               | History & Physical - vital signs X X weekly X X daily daily until discharge 2/week 2/week 2/week monthly monthly monthly X   | Pathology Review                                         | X X 2x/week X X daily daily until d/c weekly weekly weekly monthly monthly X* X   | Reticulocyte count weekly weekly until d/c weekly weekly weekly X* X* X*   | PT, PTT, Lupus anti-coagulant X   | Chemistry X X 2x/week X X QD daily until d/c X* X* X* X* X* X* X   | Iron, Transferrin, Ferritin X   |
|---------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------|-----------------------------------------------------------------------------------|----------------------------------------------------------------------------|-----------------------------------|--------------------------------------------------------------------|---------------------------------|
| 12-60 MO±3  MO                                                | X* *                                                                                                                         |                                                          |                                                                                   |                                                                            |                                   |                                                                    |                                 |
| 6-12 MO±3  MO 180±30 days 100±30 days 60±21 days 14 28±7 days | HLA Typing X                                                                                                                 | Type/Screen X q 4 days q 4 days until d/c X* X* X* X* X* | DAT*                                                                              | X* X* X* X* X*                                                             | monthly monthly monthly           |                                                                    |                                 |
| daily on days 6-10*                                           | X each cycle X daily daily until d/c                                                                                         |                                                          |                                                                                   |                                                                            |                                   |                                                                    |                                 |
| BMT -6 to -1 0                                                |                                                                                                                              |                                                          |                                                                                   |                                                                            |                                   |                                                                    |                                 |
| Treatment Phase Eligibility OnStudy Induction Pre- Pre- BMT prep                                                               | Day D 1 - 21 Induction  #2&3                                                                                                 | X                                                        |                                                                                   |                                                                            |                                   |                                                                    |                                 |
| PATIENT                                                       | X                                                                                                                            |                                                          |                                                                                   |                                                                            |                                   |                                                                    |                                 |
| Version Date: 07/23/2018                                      | 11.2 APPENDIX 2: REQUIRED STUDY EVALUATIONS                                                                                  | 11.2.1 Appendix 2 A: Patient                             | X                                                                                 |                                                                            |                                   |                                                                    |                                 |
| RBC Phenotype/Isohem Titer* X                                 |                                                                                                                              |                                                          |                                                                                   |                                                                            |                                   |                                                                    |                                 |
| X                                                             | Urinalysis X                                                                                                                 | Urine CrCl, Ca/Cr* X                                     | Urine Pregnancy* X                                                                | X                                                                          |                                   |                                                                    |                                 |
| Required Study Evaluations                                    | CBC                                                                                                                          | EKG                                                      |                                                                                   |                                                                            |                                   |                                                                    |                                 |  
119  
| PCP Prophylaxis Start              | Viral monitoring and prophylaxis Start       | Viral Monitoring (CMV, EBV, HHV6, adeno virus) weekly weekly weekly weekly weekly X* X* X* X*   | IgG Level X weekly weekly weekly weekly weekly X* X* X*   | Post-vaccine antibody titers X* X* X*   |                              |                                        |                |             |
|------------------------------------|----------------------------------------------|-------------------------------------------------------------------------------------------------|-----------------------------------------------------------|-----------------------------------------|------------------------------|----------------------------------------|----------------|-------------|
| * **                               |                                              |                                                                                                 |                                                           |                                         |                              |                                        |                |             |
| X X q 3mos q 3mos                  | Bone Marrow* X <14 days X* X* X* X* X* X* X* | CSF* X                                                                                          | DPA (>18 years old only) X                                | Endocrine function tests*               |                              |                                        |                |             |
| X* *                               | GVHD X * *                                   | X                                                                                               |                                                           |                                         |                              |                                        |                |             |
| 120                                | X                                            | X X                                                                                             | Start, hold during vincristine                            |                                         |                              |                                        |                |             |
| Bcr-abl PCR blood (28-35d post NK) | Consults                                     | Social Work X                                                                                   | Dental X                                                  | ID Monitoring & Prophylaxis             | Infectious Disease Markers X | Viral Serology (HSV, VZV, EBV, Toxo) X | PPD/Control* X | Fluconazole |
| Abbreviated Title: NK cell therapy | X                                            | X                                                                                               | Disease and GVHD Staging Evaluation X                     |                                         |                              |                                        |                |             |
| Version Date: 07/23/2018           | Echo or MUGA                                 | PFT/DLCO                                                                                        |                                                           |                                         |                              |                                        |                |             |  
| XXXX* * * *                        | X X X X q 3 mo                 | Lymphocyte Proliferation X X X X q 6 mo   | * as clinically indicated   |
|------------------------------------|--------------------------------|-------------------------------------------|-----------------------------|
| **** *                             | X                              |                                           |                             |
| 121                                | X X X                          | Anytime prior to HSCT                     |                             |
| Research Studies                   | Serum Storage X                | Immune surveillance (TBNK or flow) X      | Immune Reconstitution X     |
| Abbreviated Title: NK cell therapy | Chimerism - Peripheral Blood X |                                           |                             |
| Version Date: 07/23/2018           | Chimerism - Bone Marrow        | KIR/HLA Genotyping                        |                             |  
| 1.2.2  Appendix 2 B: Donor   |
|------------------------------|  
lbbreviated Title: NK cell therapy
/ersion Date: 07/23/2018  
| XII                    | F/U                  | X          |            |    |    |    |    |    |    |    |
|------------------------|----------------------|------------|------------|----|----|----|----|----|----|----|
| Collection             |                      |            |            |    |    |    |    |    |    |    |
| Post-                  | X                    |            |            |    |    |    |    |    |    |    |
| Collection             | X                    | X          |            |    |    |    |    |    |    |    |
| Collection             | <30 days             |            |            |    |    |    |    |    |    |    |
| Pre-                   | x                    | x          | <72 hrs    |    |    |    |    |    |    |    |
| CVL                    | sup
TL>                      | s:         |            |    |    |    |    |    |    |    |
| Pre-                   |                      |            |            |    |    |    |    |    |    |    |
| Apus
-uo                        | X*                   | X*         |            |    |    |    |    |    |    |    |
| Eligibility            | x                    | x          | x          | X  | x  | X  | x  | x  | X  | x  |
| Isohemmaglutinin Titer | Viral Serology (EBV) |            |            |    |    |    |    |    |    |    |
| Red Cell Phenotype*    |                      |            |            |    |    |    |    |    |    |    |
| History & Physical     | Infectious Disease
Markers                      |            |            |    |    |    |    |    |    |    |
| Treatment Phase        | DTM Screen           | HLA Typing | CD34 Count |    |    |    |    |    |    |    |
| Type/Screen            | Chemistry            |            |            |    |    |    |    |    |    |    |
| Urinalysis             | PT, PTT              |            |            |    |    |    |    |    |    |    |
| CBC                    |                      |            |            |    |    |    |    |    |    |    |
| Day                    |                      |            |            |    |    |    |    |    |    |    |  
| 123                                | X                       | X                            |                  |               |
|------------------------------------|-------------------------|------------------------------|------------------|---------------|
| X                                  |                         |                              |                  |               |
| X*                                 | X                       | X*                           |                  |               |
| Abbreviated Title: NK cell therapy | Chimerism (STR profile) |                              |                  |               |
| Version Date: 07/23/2018           | Urine Pregnancy*        | Child  Psychology/Psychiatry | Research Studies | Serum Storage |
| Consults                           | Social Work             | KIR testing                  |                  |               |  
^ Avoid antecubital phlebotomy if possible.* as clinically indicated  
11.3 APPENDIX 3: SCREENING AND BASELINE **EVALUATION**  
| RECIPIENT INFORMATION                                                                                                                                                                                                                                                                                                                   | DONOR INFORMATION         |         |                    |      |         |                    |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------|---------|--------------------|------|---------|--------------------|
| Name MR# Diagnosis                                                                                                                                                                                                                                                                                                                      | Stem Cell Collection Dose |         |                    |      |         |                    |
| DOB (Age) Wt(kg)/Ht(cm)/BSA(m2) Sex Test                                                                                                                                                                                                                                                                                                | Date                      | Results | Comments/Inititals | Date | Results | Comments/Inititals |
| History & Physical Immunization Records Donor Questionairre Diagnostic Pathology Blood Type Antibody Screen RBC Phenotype* Isohemmaglutinin Titer* Urinalysis CBC PT, PTT, Lupus anticoagulant Chemistry Urine CrCl Urine Ca/Cr Iron, Transferrin, Ferritin HLA: initial and confirmatory Chimerism (STR Profile) HIV-1/2 NAT HTLV-I/II |                           |         |                    |      |         |                    |  
125  
| Version Date: 07/23/2018 RPR HB S Ag HB core Ab HCV CMV IgG/IgM Toxo IgG HSV IgG Varicella IgG EBV Panel PPD/Control* Fanconi Anemia test (MDS only) Urine Pregnancy* EKG Echo (SF) or MUGA (EF) PFT/DLCO-VAcorr Staging:  PET/CT BM CSF Consults Social Work Dental Child Psych (minors only) CVL / Consent Informed Consent CIBMTR Consent IDMs-BMT <30 days of collection Workup reviewed and confirmed complete by:   |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
126  
Attending Physician date Form date: 08/15/05  
| Sample refrigerator on patient unit                                                                                                                                        | ^Courier to NCI-Frederick repository 301- 846-5893 to schedule pick-up               | ^20 ml for cell sorting (until 100% donor);  + blood and marrow. Schedule with lab X  56399                                                                                            | Sample refrigerator on patient unit                                                                                                                                                       | ^Courier to NCI-Frederick repository   | Sample refrigerator on patient unit   | ^Courier to NCI-Frederick repository   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------|---------------------------------------|----------------------------------------|
| Schedule before sending                                                                                                                                                    | X 64879                                                                              |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| Notes                                                                                                                                                                      | Blood: yellow top  (ACD) Marrow:  heparinized  syringe 10 ml ^20  ml +1-2 ml  marrow |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| 5 ml Purple top                                                                                                                                                            | (EDTA)                                                                               |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| 1st day ALC >200; 24 hours  +/- 24 hours post NK#1 and  #2 infusion. Day 28( ± 7), 60( ± 21), 100( ± 30), and every 3  months ( ± 1 mo) until 2 yrs Day –7, 0 if  ALC >200 |                                                                                      |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| 10 ml Red top                                                                                                                                                              | 4 ml red top                                                                         | 4 ml red top                                                                                                                                                                           |                                                                                                                                                                                           |                                        |                                       |                                        |
| Volume Tube                                                                                                                                                                | Day 14^, 28^+, 60, 100+, then  PRN; both whole blood and  WBC STR chimerism.         | Day prior to or morning of  EACH NK infusion, the Day  1, 2, 7, &14 ( ± 48 hr each  )after each NK cell infusion,  then D 60( ± 21), D100( ± 30), and then q 3 mos ( ± 1 mo) for 2 yrs | Day prior to or morning of  EACH NK infusion, the Day  1, 2, 7, &14 ( ± 48 hr each ) after each NK cell infusion,  then D 60 ( ± 21), D100 ( ±  30), and then q 3 mos ( ± 1 mo) for 2 yrs |                                        |                                       |                                        |
| Post-BMT                                                                                                                                                                   | Day –7, Day  0                                                                       | Day –7, Day  0                                                                                                                                                                         |                                                                                                                                                                                           |                                        |                                       |                                        |
| Pre-Study Induction Pre-BMT  Prep                                                                                                                                          |                                                                                      |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| Version Date: 07/23/2018                                                                                                                                                   | 11.4 APPENDIX 4: SUMMARY OF RESEARCH BLOODS*                                         | SAMPLE ACQUISITION TIME POINTS                                                                                                                                                         | Study Laboratory  Location                                                                                                                                                                | Prior to  Each  Cycle On-Study (Lymphocyte  PhenotypingNK Subset)                                        |                                       |                                        |
| NCI-Frederick Donor and  Recipient                                                                                                                                         | Eligibility                                                                          | On-Study                                                                                                                                                                               | On-Study                                                                                                                                                                                  |                                        |                                       |                                        |
| Clinical Path Flow  Cytometry  10/2C410                                                                                                                                    | 6-4879                                                                               | Dr. Kurlander  Hematology Lab  435-6399 Chimerism  (STR Profile)                                                                                                                       | SAIC-Frederick                                                                                                                                                                            | (301) 846-1707                         |                                       |                                        |
| 10/ C210                                                                                                                                                                   | 2-1298                                                                               |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| Cytokine  Levels                                                                                                                                                           | (IL-7/IL-15)                                                                         |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| ImmunoPhenotyping (Lymphocyte  PhenotypingTBNK panel  or NK  Subset)**                                                                                                                                                                            | TH1/TH2  cytokine  profile                                                           |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |
| Donor &  Recipient  Serum  Storage                                                                                                                                         |                                                                                      |                                                                                                                                                                                        |                                                                                                                                                                                           |                                        |                                       |                                        |  
| Sample stored and sent at room temp.  Deidentified prior to sending and label 11- C-0073–subject ID#. Send to Lihua  Hou/Carolyn Hurley at C. W. Bill Young  Marrow Program, Georgetown University,  3rd Floor, 11333 Woodglen Drive,  Rockville, MD 20852, 301-998-8900. 1 -2 mL Blood: yellow top  (ACD) tube OR 3 buccal swabs   | Sent as clinical lab (must be arranged with Dr. Roger Kurlander lab).   |                                     |                                      |                                      |                                      |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|-------------------------------------|--------------------------------------|--------------------------------------|--------------------------------------|
| Sample refrigerator on patient unit                                                                                                                                                                                                                                                                                                 | ^Courier to NCI-Frederick repository                                    | Sample refrigerator on patient unit | ^Courier to NCI-Frederick repository | ^Courier to NCI-Frederick repository | ^Courier to NCI-Frederick repository |
| 20 ml green top (sodium  heparin) Day 28 ( ± 7), 60 ( ± 21), 100( ± 30), 180 ( ± 30), and every 6  months ( ± 30d) until 2 yrs                                                                                                                                                                                                      | Preservative-free  heparin                                              | 10 ml Blood: yellow  ACD tube                                     |                                      |                                      |                                      |
| 10ml  marrow; 20ml  blood                                                                                                                                                                                                                                                                                                           |                                                                         |                                     |                                      |                                      |                                      |
| 128                                                                                                                                                                                                                                                                                                                                 | Relapse: post-subsequent  remission                                     | 28-35 days post final NK  infusion  |                                      |                                      |                                      |
| Only if DLI collection                                                                                                                                                                                                                                                                                                              |                                                                         |                                     |                                      |                                      |                                      |
| Day 100 ± 30d                                                                                                                                                                                                                                                                                                                       | Relapse                                                                 |                                     |                                      |                                      |                                      |
| Recipient                                                                                                                                                                                                                                                                                                                           | -Prior to  prep                                                         | Donor - prior to PBSC  collection   |                                      |                                      |                                      |
| Abbreviated Title: NK cell therapy                                                                                                                                                                                                                                                                                                  | NCI-Frederick Lymphocyte  Proliferation                                 | NCI-Frederick                       | Kurlander Lab                        | 435-6399                             |                                      |
| BCR abl  PCR; p210                                                                                                                                                                                                                                                                                                                  |                                                                         |                                     |                                      |                                      |                                      |
| Version Date: 07/23/2018                                                                                                                                                                                                                                                                                                            | Delbrook RN                                                             | 1W-3750                             |                                      |                                      |                                      |
| KIR  genotyping                                                                                                                                                                                                                                                                                                                     | DTM Single-Pass  Apheresis                                              | DTM Donor  Lymphocytes              |                                      |                                      |                                      |
| Blasts (Bone  Marrow or  Blood)                                                                                                                                                                                                                                                                                                     |                                                                         |                                     |                                      |                                      |                                      |  
*In the event that blood draws are limited due to patient size, research studies are listed in order of priority.^Courier to NCI-Frederick repository 301-846-5893 to schedule pick-up**May be substituted for TBNK panel if lymphocyte phenotyping cannot be scheduled.
untitled h1
11.5 appendix 5 acute gvhd

Does the patient have Acute GVHD? No / Yes o Date of the first diagnosis of aGVHD? __/__/____
Did the patient have an aGVHD flare since last exam? No Yes o Date: __/__/____
Select the appropriate stage, certainty of the system involved and indicate whether a biopsy was completed.  
| Skin   | Certainty   | Comments   | Biopsy   |
|--------|-------------|------------|----------|
| Rash   | Stage       | Y/N        |          |
| ˆ Rash not attributable to GVHD        | N/A         |            |          |
| ˆ No rash        | 0           | ˆUnlikely ˆPossible ˆ Probable ˆ Certain            | ˆNo ˆ Yes ˆ Pending          |
| ˆ <25% BSA        | 1           |            |          |
| ˆ 25-50% BSA        | 2           |            |          |
| ˆ >50%        | 3           |            |          |
| ˆ bullae and desquamation        | 4           |            |          |  
| Liver     | Certainty   | Comments   | Biopsy   |
|-----------|-------------|------------|----------|
| Bilirubin | Stage       | Y/N        |          |
| ˆ Bilirubin not attributable to GVHD           | N/A         |            |          |
| ˆ <2.0 mg/dl           | 0           | ˆUnlikely ˆPossible ˆ Probable ˆ Certain            | ˆNo ˆ Yes ˆ Pendin          |
| ˆ 2-3.0 mg/dl           | 1           |            |          |
| ˆ 3.1-6.0 mg/dl (3.1-8.0 Glucksberg)           | 2           |            |          |
| ˆ 6.1-15 mg/dl (8.1-15.0 Glucksberg)           | 3           |            |          |
| ˆ >15 mg/dl           | 4           |            |          |  
| Upper GI   | GI Tract        | Certainty   | Comments   | Biopsy   |    |
|------------|-----------------|-------------|------------|----------|----|
| Persistent | Diarrhea ml/day | Stage       | Y/N        |          |    |
| N/V        | (peds ml/m2/day) ˆ Diarrhea not attributable to                 | N/A         |            |          |    |
| GVHD       |                 |             |            |          |    |
| ˆ No (0)            | ˆ No diarrhea                 | 0           | ˆUnlikely ˆPossible ˆ            | Probable ˆ          | ˆNo ˆYes ˆPending    |
| Certain    |                 |             |            |          |    |  
  
  
  
Grade* Modified Glucksberg Criteria *Grade* IBMTR*  
1 1-2 0 0 A 1 0 0  
2 1-3 1 1 B 2 or 1-2 or 1-2 2o 0 1 1 C 3 or 3 or 3 2s 4 0 0 D 4 or 4 or 4  
| 3   | 2-4   | 2-4   | &/or   | 2-4 (1 only >2)   |
|-----|-------|-------|--------|-------------------|
| 4   | 3-4   | 2-4   | 2-4    |                   |  
Skin Liver GI Skin (max  
stage)  
Liver (max  
stage)  
GI (max  
stage)  
What was the max stage in the 1st 100 days per organ:  
| Modified                                 | Glucksberg   | CIBMTR Criteria   | Date   |
|------------------------------------------|--------------|-------------------|--------|
| Criteria                                 |              |                   |        |
| Current aGVHD Grade: Maximum aGVHD Grade |              |                   |        |  
Skin:____(0-4), Lower GI:____(0-4), Upper GI (i.e. nausea/vomiting):_____(0-1), Liver_____(0-4)
Other organ system involvement: No / Yes o  Lung o biopsy proven: No /Yes Other ____________
131 11.6 APPENDIX 6: CHRONIC GVHD EXAM AND GRADING, CLINICIAN ASSESSMENT FORM
Were Functional Performance tests completed? No Yes *(Must be greater than 4 years old)*
Select the tests performed: Walk Time: Number of laps: _______ (x 50 feet) + final partial lap: _____ feet = ______ feet walked in 2 minutes Total Distance Walked in 2 Minutes:
Grip Strength:
Grip Strength (Dominant Hand) _______________________
**Range of Motion:**
Not performed See Physical Therapy Report  
| Skin Component                                                     | Findings                     | Scoring              |
|--------------------------------------------------------------------|------------------------------|----------------------|
| ˆ Erythematous rash of any sort                                                                    |                              | ____% BSA (max 100%) |
| ˆ Moveable sclerosis                                                                    | ____ % BSA (max 100%)        |                      |
| ˆ Non-moveable sclerosis (hidebound/non                                                                    |                              | ____% BSA (max 100%) |
| pinchable) or subcutaneous sclerosis/fasciitis ˆ Ulcer(s): select the largest ulcerative lesion,                                                                    | Location: ________________   |                      |
| mark location of ulcer and measure its largest dimension in cm and | Largest dimension: _______cm |                      |  
Skin: Does the patient have skin changes? No Yes o Check and score all findings that apply.  
Eyes: Does the patient have decreased tear production? No Yes Schirmer's Tear Test completed? No Yes o  With anesthesia  Without anesthesia  
| Bilateral Schirmer's Tear Test          | Right Eye: ____________ mm of wetting   | Left Eye:   | _____________ mm of   |
|-----------------------------------------|-----------------------------------------|-------------|-----------------------|
| wetting                                 |                                         |             |                       |
| (without anesthesia) > 9 years or older |                                         |             |                       |  
Lungs: Were Pulmonary Function Tests completed? No Yes Lungs  
| FEV-1              | Single Breath DLCO (adjusted for  Hg)    % Predicted   |          |       |      |
|--------------------|--------------------------------------------------------|----------|-------|------|
| x                  | Bronchiolitis Obliterans                               |          |       |      |
| x                  | Pulmonary                                              | Function | Tests | with |
| Diffusing Capacity | % Predicted                                            |          |       |      |
untitled h1
gastrointestinal

| Gastrointestinal: Upper GI   | 0= no symptoms                                                                                                                                                                                                                                                                                                                                                           |                                                                                            |
|------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------|
| x Early satiety OR           | 1=mild, occasional symptoms, with little reduction in oral intake during the past week                                                                                                                                                                                                                                                                                   |                                                                                            |
| x Anorexia                   | OR                                                                                                                                                                                                                                                                                                                                                                       | 2=moderate, intermittent symptoms, with some reduction in oral intake during the past week |
| x Nausea/Vomiting            | 3=more severe or persistent symptoms throughout the day, with marked reduction in oral intake, on almost every  day of the past week                                                                                                                                                                                                                                     |                                                                                            |
| Score: GI/Esophageal         | 0= no esophageal symptoms                                                                                                                                                                                                                                                                                                                                                |                                                                                            |
| x Dysphagia                  | OR                                                                                                                                                                                                                                                                                                                                                                       | 1=Occasional dysphagia or odynophagia with solid food or pills during the past week        |
| x Odynophagia                | 2=Intermittent dysphagia or odynophagia with solid foods or pills, but not for liquids or soft foods, during the past  week 3=Dysphagia or odynophagia for almost all oral intake, on almost every day of the past week                                                                                                                                                  |                                                                                            |
| Score: Lower GI              | 0= no loose or liquid stools during the past week                                                                                                                                                                                                                                                                                                                        |                                                                                            |
| x Diarrhea                   | 1= occasional loose or liquid stools, on some days during the past week 2=intermittent loose or liquid stools throughout the day, on almost every day of the past week, without requiring intervention to prevent or correct volume depletion 3=voluminous diarrhea on almost every day of the past week, requiring intervention to prevent or correct volume  depletion |                                                                                            |
| Score:                       |                                                                                                                                                                                                                                                                                                                                                                          |                                                                                            |  
Mucous Membrane: Does the patient have mucosal changes? No Yes  
| Mucosal         | No cGvHD               | Mild           | Moderate         | Severe   |                          |    |                   |             |        |          |    |
|-----------------|------------------------|----------------|------------------|----------|--------------------------|----|-------------------|-------------|--------|----------|----|
| change Erythema | None                   | 0              | Mild or moderate | 1        | 0RGHUDWH                          | •    | RU                   | 2           | Severe | erythema | 3  |
| erythema (<25%) | Severe erythema (<25%) | •                |                  |          |                          |    |                   |             |        |          |    |
| Lichenoid       | None                   | 0              | Hyperkeratotic   | 1        | Hyperkeratotic           | 2  | Hyperkeratotic    | 3           |        |          |    |
| changes(<25%)   | changes(25-50%)        | changes (>50%) |                  |          |                          |    |                   |             |        |          |    |
| Ulcers          | None                   | 0              | None             | 0        | 8OFHUVLQYROYLQJ"                          | 3  | Severe            | ulcerations | 6      |          |    |
| (>20%)          |                        |                |                  |          |                          |    |                   |             |        |          |    |
| Mucoceles*      | None                   | 0              | 1-5 mucoceles    | 1        | 6-10 scattered mucoceles | 2  | Over 10 mucoceles | 3           |        |          |    |  
*Mucoceles scored for lower labial and soft palate only **Total mucosal**  
changes  
Genital: Does the patient have involvement of the genital involvement? No Yes Erythema  Lichen planus-like features  Erosions/fissures  Ulcers Female patients only:  Agglutination of the clitoral hood  Vulvar sclerosis  Vestibular tenderness  Vaginal scarring/stenosis
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health care provider global ratings

| In your opinion, do  you think that this  patient's chronic  GvHD is mild,  moderate or severe? ˆ 0=none ˆ 1= mild ˆ 2=moderate ˆ 3=severe                               | Where would you rate the severity of this patient's chronic GvHD  symptoms on the following scale, where 0 is cGVHD symptoms that are not  at all severe and 10 is the most severe cGVHD symptoms possible:   | Over the past month would you say  that this patient's cGvHD is ˆ +3= Very much better   |    |    |    |    |    |    |    |    |    |
|-------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---|----|----|----|----|----|----|----|----|----|
| 0                             | 1                                                                                                                                                                                                             | 2 | 3  | 4  | 5  | 6  | 7  | 8  | 9  | 10 | ˆ +2= Moderately better ˆ +1= A little better    |
| Not at all                    | Most severe                                                                                                                                                                                                   |   |    |    |    |    |    |    |    |    |    |
|                               | Symptoms                                                                                                                                                                                                      |   |    |    |    |    |    |    |    |    |    |
|                               | Possible                                                                                                                                                                                                      | ˆ 0= About the same ˆ -1=A little worse ˆ -2=Moderately worse   |    |    |    |    |    |    |    |    |    |
| Provider rating: ____________ | ˆ -3=Very much worse                                                                                                                                                                                                               |   |    |    |    |    |    |    |    |    |    |  
Appendix 6 (continued): Chronic GVHD Exam and Grading Does the patient have cGVHD? o No Yes First diagnosis of cGVHD? Yes No o Date of first cGVHD diagnosis __/__/__
Onset of 1st diagnosis of chronic GVHD was:  
Progressive (acute GVHD progressed directly to chronic GVHD) Interrupted (acute GVHD resolved, then chronic GVHD developed) De novo (acute GVHD never developed)
Diagnosis was based on:  histologic evidence / biopsy proven  clinical evidence both  unknown Did cGVHD flare since last visit?  N/A No Yes o Date: __/__/__
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maximum grade of chronic gvhd

Limited - localized skin involvement and/or hepatic dysfunction due to cGVHD  
Extensive - one or more of the following:
- generalized skin involvement; or, - liver histology showing chronic aggressive hepatitis, bridging necrosis or cirrhosis; or, - involvement of eye: Schirmer's test with < 5 mm wetting; or - involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy; or - involvement of any other target organ
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overall severity of chronic gvhd

Mild - signs and symptoms do not interfere substantially with function and do not progress once appropriately treated with local therapy or standard systemic therapy (corticosteroids and/or cyclosporine or FK 506)
135 Moderate– signs and symptoms interfere somewhat with function despite appropriate therapy or are progressive through first line systemic therapy (corticosteroids and/or cyclosporine or FK 506)
Severe - signs and symptoms limit function substantially despite appropriate therapy or are progressive through second line therapy  
| NIH GVHD SCORE                                                                                                                                                                                                                                                                        | SCORE 0                                                                                                       | SCORE 1          | SCORE 2   | SCORE 3   |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|------------------|-----------|-----------|
| KIN                                                                                                                                                                                                                                                                                   | No                                                                                                            | 18% BSA with     |           |           |
| Symptoms                                                                                                                                                                                                                                                                              | disease signs but  NOsclerotic  features                                                                      | 19-50% BSA OR    |           |           |
| involvement with  superficial sclerotic  features "not  hidebound" (able to  pinch)                                                                                                                                                                                                   | >50% BSA OR                                                                                                   |                  |           |           |
| deep sclerotic features  "hidebound" (unable  to pinch) ORimpaired  mobility, ulceration or  severe pruritus                                                                                                                                                                          |                                                                                                               |                  |           |           |
| Clinical features: Maculopapular rash Lichen planus-like  features Papulosquamous  lesions or ichthyosis Hyperpigmentation Hypopigmentation Keratosis pilaris Erythema Erythroderma  Poikiloderma Sclerotic features  Pruritus Hair involvement Nail involvement % BSA  involved OUTH | No                                                                                                            | Mild symptoms    |           |           |
| symptoms                                                                                                                                                                                                                                                                              | with disease signs  but not limiting oral  intake significantly                                               | Moderate         |           |           |
| symptoms with  disease signs with partial limitation of  oral intake                                                                                                                                                                                                                  | Severe symptoms                                                                                               |                  |           |           |
| with disease signs on  examination with major limitation of  oral intake                                                                                                                                                                                                              |                                                                                                               |                  |           |           |
| No                                                                                                                                                                                                                                                                                    | Mild dry eye                                                                                                  |                  |           |           |
| symptoms                                                                                                                                                                                                                                                                              | symptoms not  affecting ADL  (requiring eyedrops  < 3 x per day) OR asymptomatic  keratoconjunctivitis  sicca | Moderate dry eye |           |           |
| symptoms partially  affecting ADL  (requiring drops > 3  x per day or punctal  plugs), WITHOUT vision impairment                                                                                                                                                                      | Severe dry eye                                                                                                |                  |           |           |
| symptoms  significantly affecting  ADL (eyeware to  relieve pain) OR unable to work  because of ocular  symptoms ORloss of  vision caused by  keratoconjunctivitis  sicca                                                                                                             |                                                                                                               |                  |           |           |
| YES                                                                                                                                                                                                                                                                                   |                                                                                                               |                  |           |           |
| Mean tear test (mm): >10 6-10 <5 Not done                                                                                                                                                                                                                                             |                                                                                                               |                  |           |           |  
137  
| GI                                                                                                                               | RACT                                                                                                             | No                 | Symptoms such   |
|----------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------|--------------------|-----------------|
| symptoms                                                                                                                         | as dysphagia,  anorexia, nausea,  vomiting,  abdominal pain or  diarrhea without  significant weight  loss (<5%) | Symptoms           |                 |
| associated with mild  to moderate weight  loss (5-15%)                                                                           | Symptoms                                                                                                         |                    |                 |
| associated with  significant weight loss  >15%, requires  nutritional supplement  for most calorie needs  OResophageal  dilation |                                                                                                                  |                    |                 |
| IVER                                                                                                                             | Normal                                                                                                           | Elevated           |                 |
| LFT                                                                                                                              | Bilirubin, AP*,  AST or ALT <2 x  ULN                                                                            | Bilirubin >3 mg/dl |                 |
| or Bilirubin,  enzymes 2-5 x ULN                                                                                                 | Bilirubin or                                                                                                     |                    |                 |
| enzymes > 5 x ULN                                                                                                                |                                                                                                                  |                    |                 |  
138  
| NIH GVHD SCORE                                                                                                                                       | SCORE 0                                                                                          | SCORE 1           | SCORE 2   | SCORE 3   |
|------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|-------------------|-----------|-----------|
| UNGS                                                                                                                                                 | No                                                                                               |                   |           |           |
| symptoms                                                                                                                                             | Mild symptoms                                                                                    |                   |           |           |
| (shortness of breath  after climbing one  flight of steps)                                                                                           | Moderate                                                                                         |                   |           |           |
| symptoms (shortness  of breath after  walking on flat  ground)                                                                                       | Severe symptoms                                                                                  |                   |           |           |
| (shortness of breath at  rest; requiring 02)                                                                                                         |                                                                                                  |                   |           |           |
| FEV1 DLCO                                                                                                                                            | FEV1 60-79%                                                                                      |                   |           |           |
| OR LFS 3-5                                                                                                                                           | FEV1 <39% OR                                                                                     |                   |           |           |
| LFS 10-12                                                                                                                                            |                                                                                                  |                   |           |           |
| FEV1 40-59%                                                                                                                                          |                                                                                                  |                   |           |           |
| OR LFS 6-9                                                                                                                                           |                                                                                                  |                   |           |           |
| FEV1 >                                                                                                                                               |                                                                                                  |                   |           |           |
| 80% OR  LFS=2                                                                                                                                        |                                                                                                  |                   |           |           |
| OINTS AND ASCIA                                                                                                                                      | No                                                                                               | Mild tightness of |           |           |
| symptoms                                                                                                                                             | arms or legs,  normal or mild  decreased range of  motion (ROM)  AND not affecting  ADL          | Tightness of arms |           |           |
| or legs OR joint  contractures,  erythema due to  fasciitis, moderate  decrease ROM AND  mild to moderate  limitation of ADL                         | Contractures WITH                                                                                |                   |           |           |
| significant decrease of  ROM AND significant  limitation of ADL  (unable to tie shoes,  button shirts, dress  self etc.)                             |                                                                                                  |                   |           |           |
| ENITAL RACT                                                                                                                                          | No                                                                                               | Symptomatic       |           |           |
| symptoms                                                                                                                                             | with mild signs on  exam ANDno  effect on coitus and  minimal discomfort  with gynecologic  exam | Symptomatic with  |           |           |
| moderate signs on  exam ANDwith  mild dyspareunia or  discomfort with  gynecologic exam                                                              | Symptomatic                                                                                      |                   |           |           |
| WITH advanced signs  (stricture, labial  agglutination or severe  ulceration) AND severe pain with  coitus or inability to  insert vaginal  speculum |                                                                                                  |                   |           |           |
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11.8 appendix 8 leukemia/lymphoma response

M1 <5%  
| % blasts (at least 200 cells counted)   |
|-----------------------------------------|  
M2 5 - 25%  
M3 > 25%  
CNS Classification Acute Leukemia (Adapted from Cheson BD, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 2003;21:4642-4649)  
| CSF Cytospin   |                                             |
|----------------|---------------------------------------------|
| CNS 1          | 0 blasts on cytopsin                        |
| CNS 2          | White cell count < 5/μl, blasts on cytopsin |
| CNS 3          | White cell count > 5/μl; blasts on cytospin |
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complete response (cr)

M1 marrow, absence of peripheral blasts, absence of extramedullary sites of disease, peripheral blood neutrophil count > 1,000/PL and platelet count > 100,000/PL.  
Morphologic CR with incomplete blood count recovery (CRi): Above CR criteria without specified blood counts.  
Cytogenetic CR (CRc): In addition to above CR criteria, reversion to normal karyotype for those with previously detected cytogenetic abnormality.  
Molecular CR (CRm): In addition to above CRc criteria, normalization of previously detected molecular cytogenetic abnormality.
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partial response (pr)

M2 marrow and a decrease in the percentage of marrow blasts and absolute peripheral blast count by at least 50%, absence of extramedullary sites of disease, peripheral blood neutrophil count >
1,000/PL and platelet count > 100,000/PL.
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140 stable disease (sd)

No change in marrow classification (i.e., M status) and less than a 50% decrease to less than a 50% increase in absolute peripheral blast count or extent of extramedullary disease
Progressive Disease (PD)
Worse marrow classification (i.e., M status) with at least a 50% increase in the percentage of marrow blasts.  
Or  
No change in marrow classification (i.e., M status), but a 50% or greater increase in absolute peripheral blast count or extent of extramedullary disease
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chronic myelogenous leukemia

| Hematologic                                                | Cytogenetic             | Molecular             |
|------------------------------------------------------------|-------------------------|-----------------------|
| 0% Ph+ cells                                               | Undetectable bcr/abl by |                       |
| splenomegaly                                               | PCR                     |                       |
| peripheral WBC and WBC  < 20,000; persistent  splenomegaly | > 50% decrease in       | Detectable bcr/abl by |
| Ph+ cells                                                  | PCR                     |                       |
| No new cytogenetic                                         | Detectable bcr/abl by   |                       |
| peripheral WBC                                             | abnormalities           | PCR                   |
| New cytogenetic                                            | Detectable bcr/abl by   |                       |
| splenomegaly                                               | abnormalities           | PCR                   |  
Lymphoma (Adapted from: Cheson BD, Horning SH, Coiffier B, et al: Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. J Clin Oncol 1999;17: 1244-53)  
| Response                 | Physical Exam   | Lymph Nodes            | Lymph Node Masses       | Bone Marrow   |
|--------------------------|-----------------|------------------------|-------------------------|---------------|
| CR                       | Normal          | Normal                 | Normal                  | Normal        |
| CRu                      | Normal          | Normal                 | Normal                  | Indeterminate |
| Normal                   | Normal          | > 75% decrease x 3 mos | Normal or indeterminate |               |
| PR                       | Normal          | Normal                 | Normal                  | Positive      |
| Normal                   | > 50% decrease  | > 50% decrease         | Irrelevant              |               |
| Decrease in liver/spleen | > 50% decrease  | > 50% decrease         | Irrelevant              |               |  
PD Enlarging liver/spleen, new sites New or increased New or increased Reappearance Complete Remission (CR): Disappearance or reduction to normal size of all measurable and evaluable disease (lymph nodes <1.5 cm or nodal masses decreased by > 75% in the sum of the products of the greatest diameters lasting for > 3 months consistent with scar), negative bone marrow, non-palpable spleen. Partial Response (PR): Reduction in tumor burden by at least 50%. The sum of the products of perpendicular measurements of all (or a representative number of) masses judged to be malignant must decrease by at least 50%. None of these masses may show an increase >25% in size and no new malignant lesions should appear. Sites of disease which cannot be quantitated, such as bone marrow aspirates or lesions showing wide fluctuations prior to treatment, cannot be used to determine a PR. While defined splenic nodules can be considered measurable for the purpose of determining a PR, total spleen size cannot, although a PR is ruled out if the spleen size increases > 25%. Stable Disease: A <50% decrease to a <50% increase in the sum of the diameter product of all measurable lesions. Progressive Disease: A > 50% increase in the diameter product of any existing single lesion or the appearance of any new lesions.
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11.9 appendix 9 solid tumor

1. The CTEP response criteria for solid tumors (RECIST) outlined below will be used to assess response:
2. Only patients with measurable disease at baseline can have objective tumor response evaluated as an endpoint.  
x Measurable disease: The presence of at least one measurable lesion. If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology, if possible.  
x Measurable lesions: Lesions that can be accurately measured in at least one GLPHQVLRQZLWKORQJHVWGLDPHWHUPPXVLQJFRQYHQWLRQDOWHFKQLTXHVRU mm with spiral CT scan.  
x Non-measurable lesions: All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan), bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis cutis/pulmonis, cystic lesions, and also abdominal masses that are not confirmed and followed by imaging techniques.  
3. All measurable lesions up to a maximum of five lesions per organ and ten lesions in total, representative of all involved organs should be identified as target lesions and recorded and measured at baseline. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements. 4. All measurements should be taken and recorded in metric notation, using a ruler or calipers. All baseline evaluations should be performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of the treatment. 5. The same method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline and during follow-up. 6. Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended.  
7. Tumor Response:
x Complete Response: the disappearance of all target lesions x Partial Response: at least a 30% decrease in the sum of the longest diameter of all target lesions x Progressive disease: at least a 20% increase in the sum of the longest diameter of all target lesions x Stable disease: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease From: *Therasse, P., et al., New guidelines to evaluate the response to treatment in solid tumors. European* Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst, 2000. 92(3): p. 205-16
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11.10 appendix 10 filgrastim dosing

7KHGRQRUZLOOUHFHLYHILOJUDVWLPDVDQRXWSDWLHQWDWDGRVHRIȝJNJGD\HDFKPRUQLQJ by subcutaneous (SQ) injection beginning 4 days prior to scheduled collection. The donor and/or a family member will be taught to administer the SQ injections when possible. Otherwise, injections will be given in the POB outpatient clinic. The filgrastim should be given as early as possible after awakening in the morning. This is especially important on days 5, 6, and 7 of the injections. Filgrastim will be continued for 5, 6, or 7 days as required to complete collection of the target dose. The donor will continue filgrastim for the complete 7-day period, unless notified by the transplant team that the target dose was reached before day 7.
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adult donors (>18 years)

Timing of dose: Doses for days 1-4 should be given as early as possible after awakening in the morning, but the dose for day 5 and if necessary, days 6 and 7 must be given early in the morning, at least one hour and preferably two hours prior to starting apheresis. Filgrastim is administered according to a vial-based algorithm to reduce wastage. Two dosing algorithms are recommended for use in the Clinical Center. The standard dose algorithm uses doses in the range of 10 to 12 mcg/kg /day, with a higher dose given to lighter weight donors to improve CD34 yields. The higher dose algorithm will be utilized in this protocol as it is intended for use in (1) autologous donors who have received prior myelotoxic agents; **(2) donors whose components will undergo further processing;**
(3) protocols in which a high transplant cell dose is required (CD34 > 8 x106**); and**
(4) situations with large weight discrepancy between donor and recipient (recipient > donor). The total dose is capped at 1200 mcg/kg/day. Higher-Dose Filgrastim Algorithm:  
| Donor Wt    | Total Daily Filgrastim Dose (range)   |                       |
|-------------|---------------------------------------|-----------------------|
| 38 - 48 kg  | 600 mcg                               | (12.5 to 15.8 mcg/kg) |
| 49 - 56 kg  | 780 mcg                               | (13.9 to 15.9 mcg/kg) |
| 57 - 60 kg  | 900 mcg                               | (15.0 to 15.8 mcg/kg) |
| 61 - 67 kg  | 960 mcg                               | (14.3 to 15.7 mcg/kg) |
| 68 - 108 kg | 1080 mcg                              | (10.0 to 15.9 mcg/kg) |
| > 109 kg    | 1200 mcg                              | (11.0 or less)        |  
Predictable side effects of filgrastim, including headache, bone pain, and myalgia, may be treated with acetaminophen or ibuprofen.
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11.11 appendix 11 engraftment syndrome

Diagnosis of Engraftment Syndrome (ES) is made based on the presence of all three (\#) major criteria, or two (2) major criteria with one or more minor criteria.  
Major Criteria  
x 7HPSHUDWXUHƕC with no identifiable infectious etiology x Erythrodermatous rash involving more than 25% of body surface area and not attributable to a medication x Noncardiogenic pulmonary edema, manifested by diffuse pulmonary infiltrates consistent with this diagnosis, and hypoxia.
Minor Criteria  
x +HSDWLFG\VIXQFWLRQZLWKHLWKHUWRWDOELOLUXELQPJGORUWUDQVDPLQDVHOHYHOV
two times ULN
x 5HQDOLQVXIILFLHQF\VHUXPFUHDWLQLQHWZRWLPHEDVHOLQH
x :HLJKWJDLQRIEDVHOLQHERG\weight x Transient encephalopathy unexplainable by other causes.
,QDGGLWLRQ(6VKRXOGRFFXUZLWKLQKRXUVRIHQJUDIWPHQWGHILQHGDVDQHXWURSKLOFRXQWRI 500/μL for 2 consecutive days).  
x TBI will be delivered to a total midplane dose of 12Gy and median lung dose of 6Gy.  
Radiation will be fractionated twice daily over 3 days (days -6, -5, -4). Opposed lateral fields with lung compensation will be treated to 2 Gy for each fraction to a total cumulative dose of 12Gy.  
x Mediastinal fields will be treated AP-PA concurrently with the opposed lateral fields at a dose of 100cGy twice daily to bring the mediastinal dose to 12Gy with a median lung dose of 6 Gy.  
x Fractions will be delivered with at least a 6 hour interfraction interval. Gonadal shielding will not be used. Head and neck compensation and other technical modifications may be made at the discretion of the treating radiation oncologist.  
x For patients with CNS positive disease at any time after diagnosis, CNS boost may be delivered unless contraindicated. The final decision of appropriateness of delivering the boost and boost dose will be made by the PI in consultation with the treating radiation oncologist. The CNS boost will be delivered as a 6 Gy boost in once daily 2 Gy fractions. The boost will be delivered prior to TBI.  
x Patients with sites identified by nuclear imaging or other clinically accepted diagnostic tests may receive a boost to these areas as clinically indicated at any time point pre- or post transplantation.  
11.13 APPENDIX 13: CALCULATION OF IDEAL BODY WEIGHT AND DOSE ADJUSTMENTS Formulation for deriving the weight to be used in dose calculations in morbidly obese candidates.
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1. definition

Obesity is defined as a > 125% of IBW.  
2. **Calculation of ideal body weight** is performed using the standard, published formula:
Male: 50 + 2.3(Hgt - 60) where Hgt is in inches, and the result is expressed in kg.  
ex. The ideal weight of a 5'10" male = 50 + 2.3(10) = 73 kg.  
Female: 45.5 + 2.3(Hgt - 60), where height is in inches, and the result is in kg.  
3. Dose adjustments for pre-transplant myeloablative chemotherapy will be based on an adjusted weight.  
Adjusted weight =1.25 x IBW
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4. calculation of the "practical

Calculate the midway point, halfway between the actual and ideal body weights (ie the average of the two numbers). This is the "practical weight" which may be used for calculating the targeted cell dose.
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example

Patient's actual weight = 143 kg. Patient' s actual height 173 cm = 69 in IBW formula = 50 + 2.3(9) = 70.7 kg Midway point between 70.0 and 143 = 107 kg.  
The weight we would use in targeting cell dose is 107 kg.