bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic Bone Marrow Transplantation in a Child with Hemophilia A and Severe Aplastic Anemia.
Authors: Ostronoff Mauricio , Florencio Rodrigo , Ostronoff Fabiana , Campos Gilma , Arruda Sandra , Vaz Claudia , Souto Ana Patricia , Sucupira Alexandre , Domingues Mariana Coutinho , Calixto Rodolfo , Matias Kleber , Clemente Tagliari 
Published: April 2020

Abstract
Hemophilia A is a blood clotting disorder characterized by a mutation of the factor VIII (FVIII) gene, leading to a deficiency in FVIII. It is the most common type of hemophilia. Inheritance is X-linked; hence males are affected while females are carriers or very rarely display a mild phenotype. 1:10,000 males are affected. We describe a child with a rare association of congenital hemophilia A and acquired severe aplastic anemia (SAA) who was successfully treated with allogeneic bone marrow transplantation (allo-BMT). A 6-year old male, SG, was diagnosed with hemophilia A (FVIII 3%) at 6-month old when he presented with right knee hemarthroses and psoas muscle hematoma. His maternal grandfather was hemophiliac. Since his diagnose, FVIII was infused on average once a month, generally due to hemarthroses and bleeding secondary to trauma. In July 2004, pt presented with progressive pancytopenia. In January 2005 CBC showed: Hb 7g/dl, Ht 22%, WBC 1000/μl (absolute neutrophil count 250/μl) and PLT 23,000/μl. Bone marrow aspirate and biopsy were consistent with SAA. DEB test was negative. Since then he was poly-transfused with PLT and RBC due to increased bleeding tendency, especially hematoma and petechiae. In July 2005 he underwent an allo-BMT from his HLA-identical non-hemophiliac 5-year old brother. For catheter implantation pt received PLT transfusion to achieve a PLT level greater than 50,000/mm3 and 60 units/kg of FVIII to achieve an initial level of 100% followed by 30 units/kg every 12 hours to maintain it continuously at greater than 50% for 3 days. Conditioning consisted of cyclophosphamide 50mg/day from D-5 to D-2 and thymoglobulin 5mg/kg from D-3 to D-1. Cyclosporine and a short course of methotrexate were given for GVHD prophylaxis. 3,5x108 mononuclear cells/kg were infused. Allo-BMT was uneventful. Neutrophil engrafted on D+15 and megakaryocyte (&gt;50,000/mm3) on D+38. During the transplant PLT were kept at greater than 30,000/mm3 with PLT transfusion every 2 days. FVIII was infused when there was more than 2 cm increase in the knee perimeter or any other abnormal bleeding, especially at the catheter implantation site. 6 months after allo-BMT the child is well, with a normal CBC and coagulation tests similar to pre-BMT. Hemophilia and AA association is rare, and to our knowledge, this is the first allo-BMT in a hemophiliac patient to be reported.
Allogeneic Transplant with Standard Conditioning, Reduced Intensity, or Non-Myeloablative Conditioning Regimen for Multiple Myeloma (MM).
Authors: Sahebi Firoozeh , Kogut Neil M. , Spielberger Ricardo , Falk Peter M. , Nademanee Auayporn P. , Popplewell Leslie , Maloney David G. , Rodriguez Roberto , Krishnan Amrita , Nakamura Ryotaro , O’Donnell Margaret R. , Pablo Parker M. , Smith Eileen P. , Stein Anthony S. , Snyder David S. , Zain Jasmine M. , Qian Dajun , Forman Stephen J. , Somlo George 
Published: April 2020

Abstract
We conducted a retrospective analysis of 58 patients who underwent allogeneic stem cell transplantation at our center from 1994 to 2004. Among these 58 patients, 56 received allogeneic transplant from HLA matched sibling and 2 patients received transplant from a matched unrelated donor. Fourteen patients received standard transplant (ST) using different myeloablative chemotherapy regimens with or without fractionated total body irradiation (FTBI, 9 patients). Thirty four patients underwent tandem transplants (autologous transplant followed by non-myeloablative allogeneic transplant; auto-allo group). Conditioning consisted of melphalan (200mg/m2) prior to the autograft, and TBI (200cGy) as part of non-myeloablative allograft. Ten patients received reduced intensity conditioning (RIC) allograft with fludarabine (25 mg/m2 x 5 days) and melphalan (140 mg/m2). The source of stem cells was bone marrow in 14 patients (ST) and peripheral blood in 44 patients. Median age was 44 yrs for ST group (range 25–53), 51 yrs for auto-allo group (range 38–66) and 48 yrs for RIC group (range 43–64). Median follow up was 2.8 yrs for ST group (range 0.2–13.0), 2.8 yrs for auto-allo group (range 0.2–5.0) and 1.1 yrs for RIC group (range 0.2–3.6). There was a statistically significant difference in overall survival (OS) between the different groups with an observed 2 year OS of 50% in the ST group, 76% in the auto-allo group and 42% in RIC group (P=0.04). Disease free survival (DFS) was also statistically different between the different groups at 2 years: 21% in the ST group, 59% in auto-allo group, and 40% in RIC group (p=0.04). The incidence of severe grade III–IV acute graft versus host disease (GVHD) was less in auto-allo group (6% & 6%), as compared to the RIC group (20% & 10%) and ST group (14% & 14%). 2 year non-relapse mortality rates were 43% in ST, 20% in auto-allo group and 29% in the RIC group, and relapse-related mortality rates were 7% in ST group, 4% in auto-allo group and 29% in the RIC group. There was no statistically significant correlation between GVHD and DFS. Our data suggest an improvement in DFS and OS following tandem auto-non-myeloablative allotransplantation or RIC allotransplantation as compared to standard allogeneic transplant. The better outcome following an auto-allograft approach suggests that cytoreduction prior to an allograft may be important for optimal disease control in MM.
Modification or Dose or Treatment Duration Has No Impact on Outcome of AML in Older Patients: Preliminary Results of the UK NCRI AML14 Trial.
Authors: Burnett Alan K. , Milligan Donald W. , Prentice Archie G. , Goldstone Anthony H. , McMullin Mary F. , Hills Robert K. , Wheatley Keith 
Published: April 2020

Abstract
The NCRI AML14 Trial was devised for patients aged over 60 years with de novo or secondary AML or high risk MDS (defined as &gt;10% blasts). There was a non-intensive option which compared Low Dose Ara-C vs Hydroxyurea each with or without All-Trans Retinoic Acid which has been reported previously (Burnett et al Blood2004: 249a), and an intensive approach which we now report. This compared two dose levels of Daunorubicin (50mg/m2 vs 35mg/m2) and Ara-C (200mg/m2 vs 400mg/m2) within a Daunorubicin/Ara-C (3+10) followed by (3+8) schedule. After a 3rd course (MidAC: Mitoxantrone/Ara-C), patients were randomised to receive or not a 4th course (ICE: Idarubicin/Ara-C/Etoposide). In addition some patients (n=200) were randomised to receive PSC-833 in addition to Dauno 35. The results of this randomisation have been reported previously (Burnett et al Blood 2003614a).
A total of 1273 patients entered the trial between December 1998 and closure in May 2005, from 136 centres. Follow-up is complete to 1st April 2005, with median follow-up of 33 months. The median age was 67 (range 44-88). Cytogenetics were known for 67% of patients: of these, 3% had favourable, 74% intermediate and 23% adverse cytogenetics. 72% had de novo AML, 17% had secondary disease and 11% had high risk MDS. The overall CR rate was 62% and the Relapse Risk (RR), Disease Free Survival (DFS), and Overall Survival (OS) were 84%, 13%, and 13% at 5 years. 896 patients were randomised to D50 vs D35. No significant differences were found in CR (63% vs 64% OR 1.04 (95% CI 0.78–1.37)), RR (84% vs 85% OR 0.85 (95%CI 0.65–1.06)), DFS 14% vs 13% OR 0.86 (95% CI 0.70–1.06)), or OS (15% vs 13% OR 0.92, 95% CI (0.72–1.08)). Likewise, there were no significant differences in outcome for the 1264 patients randomised to Ara-C 200 vs 400: CR (62% vs 62% OR 1.00 (95% CI 0.80–1.27)), RR (84% vs 85% OR 1.14 (95% CI 0.95–1.37)), DFS (13% vs13% OR 1.14 (95% CI 0.96–1.14)) or OS (13% vs 12% OR 1.00 (95%CI 0.87–1.14)). In the 255 patients randomised to a total of 4 vs 3 courses the RR (83% vs 76% OR 0.90 95%CI 0.66–1.24), DFS (16% vs 18% OR 0.94 95% CI 0.69–1.28) and OS (23% vs 22% OR 1.05, 95% CI 0.75–1.47) were not significantly different.
From this preliminary analysis we conclude that there is no difference between a reduced dose of Daunorubicin (35mg/m2) compared with standard dose, or between enhanced Ara-C dose (400mg/m2) or standard dose and the confidence intervals are consistent with at most a moderate difference in treatment effect. We found no benefit for giving more than 3 courses of total treatment to patients in this age group, although the confidence intervals here do not rule out moderate, but potentially meaningful differences.
Unrelated Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies.
Authors: Gao Chunji , Da Wanming , Zhang Bolong , Han Xiaoping , Yu Jing , Zhang Yizhuo , Li Honghua , Bo Jian , Zhu Haiyan , Jin Haijie , Wu Xiaoxiong , Wang Quanshun , Li Suxia , Huang Wenrong , Yu Li 
Published: April 2020

Abstract
Objiective To explore feasibility and efficacy of unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in treatment of hematologic malignancies.
Methods Ten patients with hematologic malignancies undewent high resolution DNA based typing HLA-matched or 1 locus mismatched UD-PBSCT. Busulfan, cyclophosphamide, Ara-C, MeCCNU and antithymocyte globulin (ATG) were used for preparative regimen in all cases. All patients received mycophenolate mofetile, cyclosporin A and short-term methotrexate with CD25 antibody as the graft-versus-host disease (GVHD) prophylaxis.
Results The results showed that rapid engraftment was observed in all cases who presented full donor chimerism at 28 days post transplantation by STR-PCR. The median time of neutrophil recovery &gt;0.5×109/L, platelet recovery &gt;20×109/L was observed at 13, 17.5days respectively post transplantation. The incidence of acute GVHD was 3/10 cases (1case with grade I was recovery by himself, 1case with grade III was cured, 1case with grade VI was died).
Conclusion It is concluded that above-mentioned conditioning and GVHD prophylaxis are effective approaches for unrelated donor peripheral blood stem cell transplantation in treatment of hematopoietic malignancies.
Preliminary Experience with Haploidentical Stem Cell Transplantation for Children with Sickle Cell Disease and Stroke.
Authors: Woodard Joseph , Wang Winfred , Barfield Raymond , Hale Gregory , Horwitz Edwin , Leung Wing , Yusuf Usman , Ware Russell , Handgretinger Rupert , Cunningham John M. 
Published: April 2020

Abstract
Hematopoietic stem cell transplantation has been shown to be curative for approximately 83% of symptomatic children with sickle cell disease who have undergone the procedure. Despite these encouraging results, only 15% of children with symptoms that might merit consideration for transplantation have an available, unaffected HLA-matched sibling donor, severely limiting this therapeutic option. To address this problem, we developed a protocol for children with SCD and stroke using reduced-intensity conditioning and CD34-selected peripheral blood stem cells from haploidentical parental donors. We now report our preliminary experience using this approach in three children with SCD and stroke. After a chemotherapy-only conditioning regimen of fludarabine 150–200 mg/m2, thiotepa 10 mg/kg, i.v. busulfan targeted to a steady state concentration of 900 ng/ml, and OKT3, patients received an average of 27.2 x 106 CD34+cells/kg and 1.1 x 104 CD3+ cells/kg. Two patients required additional immunosuppression with methylprednisolone and OKT3 followed by a CD34 boost after graft rejection. One of these two had durable long-term engraftment, while one had a second rejection. Two of three patients have durable donor engraftment 20 and 24 months after transplantation, respectively. Donor T-cell chimerism evolved from predominantly host-derived to donor-derived over a number of months. One patient developed grade I acute GVHD and none developed chronic GVHD. Two engrafted patients have had no further SCD events. Both have recovery of immune function with normal CD4+ T-cell counts and normal thymic function. This preliminary experience demonstrates the feasibility of using mismatched parental donors for children with sickle cell disease. Future studies will focus on achieving reliable donor engraftment through additional graft manipulation strategies.
Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) for Myelofibrosis (MF).
Authors: Takagi Shinsuke , Miyakoshi Shigesaburo , Oota Yasunori , Kato Daisuke , Kawano Tomomi , Kusumi Eiji , Matsumura Tomoko , Yuji Koichiro , Uchida Naoyuki , Masuoka Kazuhiro , Wake Atsushi , Yoneyama Akiko , Taniguchi Shuichi 
Published: April 2020

Abstract
Introduction: Although allogeneic hematopoietic stem cell transpslantation is the only curative treatment for patients with MF, the potential role of cord blood transplantation remains still unclear. We report the results of RICBT for hematological diseases with primary and secondary MF.
Patients and Methods: We reviewed medical records of 179 patients with advanced hematological diseases who received RICBT between March 2002 and June 2005 at our institution. Of 179 patients, pre-transplant bone marrow specimens were available for 82 patients. We evaluated bone marrow specimens by aspiration and trephine biopsy. Aspiration may be not enough to evaluate marrow fibrosis, but could reflect fibrotic change in bone marrow (Am J Clin Pathol1971; 56: 25). One patient had primary MF and 47 had secondary. Underlying diseases for secondary MF included AML/MDS (35), ALL (6), CML (1), severe aplastic anemia (2), malignant lymphoma (2), essential thrombocythemia (1). For staging of MF, we used pathological criteria by Michiels (Int J Hematol2000; 76: 133). MF0: no reticulin fibrosis (n=35), MF1: slight reticulin fibrosis (n=38), MF2: marked increase in reticulin and slight to moderate collagen fibrosis (n=8), MF3: advanced collagen fibrosis-osteosclerosis (endophytic bone formation) (n=1). Median age of the patients was 55 years (17–71). Most of the conditioning regimens were fludarabine 125 mg/m2, melphalan 80 mg/m2 and TBI 4 Gy. GVHD prophylaxis was cyclosporine (n=35) or tacrolimus (n=47). The median number of infused nucleated cells: 2.66 x 10e7 cells (1.67_5.24 x 10e7); CD34 positive cells: 0.69 x 10e5 cells (0.11_3.90 x 10e5); HLA disparity: 6/6 (n=4), 5/6 (n=14), 4/6 (n=60), 3/6 (n=4).
Results: Neutrophil engraftment at day 50 was observed in 70.8 % with MF (median 22 days) and 73.7 % without MF (median 22 days). Platelet engraftment at day 100 was observed in 40.0 % with MF (median 42 days) and 60.0 % without MF (median 40 days). There was no statistical significance in neutrophil and platelet engraftment between patients with MF and without MF. Of 48 patients, 6 showed biopsy-proven MF greater than stage 1. Their neutophil and platelet engraftment was observed in 100 % (median 22 days) and 66.7 % (median 48 days), respectively. Cumulative incidence of acute GVHD (II–IV) was 17 % with MF and 28 % without MF. There was no statistical significance. The estimated OS was 25 % with MF and 52 % without MF (p=0.03) (Figure 1). Most cause of death with MF was relapse.
Conclusion: Despite of marrow fibrosis, neutophil and platelet engraftment was not influenced. These results have suggested that RICBT is feasible for MF. However, the existence of MF could be poor prognostic factor of RICBT for hematological diseases due to relapse.
Figure Figure
Single-Institute Analysis of Allogeneic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.
Authors: Kobayashi Takeshi , Yamashita Takuya , Sakai Miwa , Okuyama Yoshiki , Ohashi Kazuteru , Akiyama Hideki , Hiruma Kiyoshi , Sakamaki Hisashi 
Published: April 2020

Abstract
Purpose
We report the outcomes of allogeneic stem cell transplantation (SCT) for the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in a single center.
Patients and Methods
Between August 1993 and March 2005, 36 patients with Ph+ALL received SCT at Tokyo Metropolitan Komagome Hospital. The median age was 41 years (range; 17 to 60 years). All patients received myeloablative conditioning regimen (cytosine arabinoside, cyclophosphamide and fractionated 12Gy total-body irradiation). Stem cell source of SCT was 14 related donors (bone marrow [n=9] and peripheral blood stem cell [n=5]) and 22 unrelated donors (bone marrow [n=13] and cord blood [n=9]).
Results
Seventeen (47%) of 36 patients are alive at a median of 2.16 years (range; 1.0 to 3.3 years) after transplantation. Three years overall survival (OS) and disease free survival (DFS) for all patients are 42.3% and 35.4%, respectively. Three years OS and DFS are 55.4% and 46.4% for the 24 patients in complete remission (CR) at transplantation, while 36.4% (p&lt;0.001) and 16.7% (p&lt;0.01) for the 12 patients in non-CR, respectively. Stem cell source and patients age do not affect the outcomes. The higher white blood cell counts at diagnosis are associated with poor OS (p=0.003). The median duration from diagnosis to SCT is 7 months (range; 3 to 29 months). Three years OS of the patients who received SCT within 7 months from diagnosis is better than that of the others (59.3% vs. 31.1%, p=0.019).
Conclusion
This analysis suggests that shorter duration between diagnosis and transplantation improve the clinical outcomes of SCT for Ph+ALL, especially performed in CR.
Prognostic Factors for the Engraftment in Cord Blood Transplantation: With Units Shipped from Single Cord Blood Bank, Tokyo Cord Blood Bank.
Authors: Nagamura-Inoue Tokiko , Yan Cui , Satomi Aya , Mugishima Hideo , Asano Shigetaka , Takahashi Tsuneo , Kodo Hideki 
Published: April 2020

Abstract
The better selection of cord blood (CB) unit in recent varied cord blood transplantation (CBT) is crucial for the success of CBT, although it is difficult to compare the units from different cord blood bank (CBB). Here, we analyzed the prognostic factors by age for engrafment in CBT with the units shipped from single CBB, Tokyo Cord blood bank.
Patients and Methods: Units were all processed by HES centrifugation method and cryopreserved with 10% DMSO and Dextran 40 in Tokyo CBB. CD34 was analyzed by gating CD45dim CD34+ with DNA dye or 7-AAD in Trucount beads tube (BD). Patients characteristics are shown in table. Group I included 58u for malignancies and 25 for non-malignancies. Group III included 22 full(Full) vs.22 reduced intensity (RI) conditioniong regimen for malignancies and remaining ones with further reduced intensity regimens. RI regimen consisted maily with reduced dose of TBI (&lt;8Gy) and BU/Melphalan with fludarabin.
Results: Myeloid engraftment in malignancies with Full regimen was seen at 84.3%(median 28days) in Group I, 82.5%(25days) in Group II and 73.0%(30days) in Group III, respectively, whereas with RI regimen in Group III was 67.8%(24days). The patients with non-malignancies in Group I showed 75.0% (26days) of engraftment by Full regimen(n=12) and 100% (24days) by RI regimen(n=8), respectively. HLA disparities had no significant influence on the engraftment in Group I and II. The dose effects of NC and CD34+ cells on the rate and the speed of engraftment were seen in Full regimen in Group I and II for malignancies. Critical dose of CD34+ cells seemed 0.8x105/kg. Even in Group I(children), the patient with CD34+ less than 0.8x105/kg showed 79.6%(43days), whereas those with more than 0.8x105/kg, 85.7%(24days). There was no difference of speed and rate of engraftment between the patients with CD34+ cells 0.8~1.6x105/kg and those with more than 1.6x105/kg. Interestingly, this effect vividly influenced on the engraftment in the patients with RI regimen of Group III. The patients with CD34 + with less than 0.8x105/kg showed only 22.9% of final engraftment, whereas those with over 0.8x105/kg 100% (19 days) in Group III. The dose of CD34+ had some influeced on the survivals, although the main prognostic factors on the long-term survivals was the risk factor of malignancy and age.
Conclusion: CD34+ cell dose should be given high priority for the selection of CB unit, especially in reduced intensity regimen.
Patients Characteristics No. of Patients Group I ( ~ 15 y.o.) n=83 Group II (15 ~ 50 y.o.) n = 76 GroupIII (51 y.o. ~) Age y.o. 5.23±4.81 33.9±10.4 58.3±12.8 BM (kg) 19.7±14.2 52.0±9.1 54.0±13.5 Dose of NC (x10^7/kg) 6.17±3.98 2.63±0.66 2.76±1.10 Dose of CD34 (x10^5/kg) 1.80±1.75 0.81±0.46 0.91±0.95 HLA mismatch 0 18 5 4 (rejection direction) 1 51 33 19 2 14 35 23 3 0 3 0
Immunophenotypical Minimal Residual Disease as a Short Term Endpoint for Monitoring Effects of Targeted Inhibitors in Acute Myeloid Leukemia.
Authors: Hess Corine J. , Feller Nicole , Denkers Fedor , Merle Pauline A. , Ossenkoppele Gert J. , Waisfisz Quinten , Schuurhuis Gerrit Jan 
Published: April 2020

Abstract
At present, a large number of clinical trails make use of inhibitors that target leukemia specific defects, such as BCR-ABL, c-kit mutations or tandem duplications in the FLT3 gene (FLT3-ITD). Irrespective of their target, these studies all share the need for a short term read out parameter. Nowadays remission rate, remission duration and survival are used as a final read out in such studies. Previously we have observed that after different cycles of chemotherapy the frequencies of Minimal Residual Disease (MRD) cells, as determined using aberrant immunophenotypes, is highly correlated with clinical outcome (Feller, Leukemia2004; 18:1380). Based on these observations we have examined whether MRD might function as the desired short term read out. As a proof of principle we have examined this for FLT3-ITD. We determined ITD status in bone marrow (BM) samples of 162 newly diagnosed AML patients by gel electrophoresis and GeneScan analysis. Frequencies of MRD cells were assessed in 316 BM samples of these 162 patients: 146 after 1st, 95 after 2nd and 75 after 3rd cycle of chemotherapy using LAP technology. As also shown by others, FLT3-ITD at diagnosis was predictive for OS (p=0.04, B (exp)=1.80 and RFS (p=0.05, B (exp)=1.91). This study now shows in addition, that in remission patients after 1st cycle (70% of all patients), the presence of an ITD (21% of the cases) at diagnosis is associated with 8.5-fold higher MRD% (median 0.34%, range 0.01-3.3%), compared to wild type FLT3 (median 0.04%, range 0.01–1.27%), p=0.020. Similar to our previous observations, MRD level taken as a continuous variable in the total patient group after 1st cycle was inversely correlated to OS (p=0.041) and RFS (p=0.0001). Using previously described clinically relevant MRD cut-offs, such 8.5-fold differences in frequencies of MRD cells resulted in significant differences in OS and RFS, in the whole range of MRD frequencies (0.01-6.8%). Based on this we conclude that efficacy of FLT3 inhibitors in terms of survival can be predicted with MRD frequency after 1st cycle of therapy that includes the inhibitor. MRD frequency may thus serve as an early read out parameter, for efficacy of targeted therapy in AML.
Figure 1. MRD% in FLT3+ and FLT3− patients who achieved remission Figure 1. MRD% in FLT3+ and FLT3− patients who achieved remission