nma allogeneic hematopoietic cell transplant in hematologic cancer/disorders

Conditions: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Fanconi Anemia; Aplastic Anemia

Summary: rationale: giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. it also stops the patient's immune system from rejecting the donor's stem cells. the donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). giving an infusion of the donor's t cells (donor lymphocyte infusion) after the transplant may help increase this effect. sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. giving immunosuppressive therapy before or after the transplant may stop this from happening. purpose: this phase ii trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.

objectives: * determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia. * determine clinical response and overall outcome of patients treated with this regimen. * determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen. outline: * preparative regimen: * matched related and unrelated donor transplantation: * patients receive cyclophosphamide iv over 2 hours on days -5 and -4 and fludarabine iv over 30 minutes on days -5 to -1. * cord blood transplantation: * patients receive the same regimen as above plus anti-thymocyte globulin iv over 4 hours on days -3 to -1. * graft-vs-host disease (gvhd) prophylaxis: * matched related and unrelated donor transplantation: * patients receive oral tacrolimus (or iv) once daily and oral mycophenolate mofetil (mmf) (or iv) twice daily on days -1 to 60 followed by tapering\* of this regimen. patients then receive methotrexate iv on days 1, 3, and 6. * cord blood transplantation: * patients receive tacrolimus and mmf in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover. * allogeneic stem cell reinfusion: patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. patients then receive sargramostim (gm-csf) subcutaneously daily beginning on day 7 and continuing until blood counts recover. * donor lymphocyte infusion (dli): patients not converting to 100% donor t-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and mmf withdrawal may receive dli every 8 weeks for up to 3 infusions. cord blood recipients do not receive dli. patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years. projected accrual: a total of 30-60 patients will be accrued for this study within 6-7 years.

Eligibility criteria:
disease characteristics: * diagnosis of aplastic anemia * severe disease * failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin or * histologically confirmed hematologic malignancy including the following: * acute leukemia * any of the following types: * acute myeloid leukemia (aml) with antecedent myelodysplastic syndromes * secondary aml * aml with high-risk cytogenetic abnormalities * acute lymphoblastic leukemia with high-risk cytogenetic abnormalities * resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen or * in first remission at high risk of relapse * chronic myelogenous leukemia * chronic phase meeting at least 1 of the following criteria: * failed imatinib mesylate * failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week * unable to tolerate interferon * accelerated phase (blasts less than 20%) * myeloproliferative and myelodysplastic syndromes * myelofibrosis (after splenectomy) * refractory anemia * refractory anemia with excess blasts * chronic myelomonocytic leukemia * lymphoproliferative disease * chronic lymphocytic leukemia * symptomatic disease after first-line chemotherapy * low-grade non-hodgkin's lymphoma (recurrent or persistent) * symptomatic disease after first-line chemotherapy * multiple myeloma * progressive disease after autologous stem cell transplantation * waldenstrom's macroglobulinemia * failed 1 standard regimen * non-hodgkin's lymphoma meeting the following criteria: * intermediate or high grade * controlled and chemosensitive disease * first remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse * hodgkin's lymphoma * relapsed and chemosensitive disease * not eligible for standard myeloablative allogeneic stem cell transplantation * availability of any of the following donor types: * related donor matched at 5 or 6 hla antigens (a, b, dr) * unrelated donor fully matched by molecular analysis at a, b, drb1, and dqb1 loci * single antigen mismatch at c allowed * cord blood that is 4, 5, or 6 match with recipient hla antigens (a, b, dr) note: no syngeneic donors permitted * no uncontrolled cns disease (for hematologic malignancies) note: a new classification scheme for adult non-hodgkin's lymphoma has been adopted by pdq. the terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. however, this protocol uses the former terminology. patient characteristics: age * 4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation) * 4 to 60 (if unrelated cord blood transplantation) performance status * karnofsky \> 50% life expectancy * not specified hematopoietic * not specified hepatic * bilirubin less than 3 times normal * alkaline phosphatase less than 3 times normal * ast/alt less than 3 times normal * no child's class b or c liver failure renal * creatinine clearance greater than 40 ml/min cardiovascular * cardiac ventricular ejection fraction at least 35% by muga * no cardiovascular disease pulmonary * dlco at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv antibody negative * no uncontrolled diabetes mellitus * no active serious infection * no other disease that would preclude study therapy * no other concurrent malignancy except non-melanoma skin cancer * no concurrent serious psychiatric illness prior concurrent therapy: biologic therapy * see disease characteristics * patients may have received a prior autologous blood or marrow transplantation (bmt) * at least 6 months since prior allogeneic bmt chemotherapy * see disease characteristics * at least 2 weeks since prior chemotherapy, radiation or surgery endocrine therapy * not specified radiotherapy * at least 2 weeks since prior radiotherapy surgery * at least 2 weeks since prior surgery

Keywords: accelerated phase chronic myelogenous leukemia chronic myelomonocytic leukemia primary myelofibrosis de novo myelodysplastic syndromes chronic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia refractory anemia with excess blasts stage i multiple myeloma stage ii multiple myeloma stage iii multiple myeloma waldenstrom macroglobulinemia stage iii adult lymphoblastic lymphoma stage iv adult lymphoblastic lymphoma noncontiguous stage ii adult burkitt lymphoma stage iii adult burkitt lymphoma stage iv adult burkitt lymphoma recurrent adult hodgkin lymphoma adult acute myeloid leukemia in remission secondary acute myeloid leukemia recurrent childhood acute lymphoblastic leukemia recurrent adult acute myeloid leukemia childhood acute lymphoblastic leukemia in remission adult acute lymphoblastic leukemia in remission noncontiguous stage ii adult lymphoblastic lymphoma refractory multiple myeloma refractory anemia refractory chronic lymphocytic leukemia previously treated myelodysplastic syndromes secondary myelodysplastic syndromes grade 1 follicular lymphoma grade 2 follicular lymphoma recurrent/refractory childhood hodgkin lymphoma recurrent adult acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia childhood acute myeloid leukemia in remission childhood chronic myelogenous leukemia atypical chronic myeloid leukemia myelodysplastic/myeloproliferative disease, unclassifiable recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone b-cell lymphoma splenic marginal zone lymphoma adult acute myeloid leukemia with t(8;21)(q22;q22) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with 11q23 (mll) abnormalities adult acute myeloid leukemia with t(15;17)(q22;q12) childhood myelodysplastic syndromes