Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 799-803 ◽  
Author(s):  
Seiji Kojima ◽  
Takaharu Matsuyama ◽  
Shunichi Kato ◽  
Hisato Kigasawa ◽  
Ryoji Kobayashi ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Dna Typing ◽  
Hla Class I ◽  
Severe Aplastic Anemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Improved Outcomes ◽  
Unrelated Donors ◽  
Acquired Severe Aplastic Anemia

Abstract We retrospectively analyzed results for 154 patients with acquired severe aplastic anemia who received bone marrow transplants between 1993 and 2000 from unrelated donors identified through the Japan Marrow Donor Program. Patients were aged between 1 and 46 years (median, 17 years). Seventy-nine donor-patient pairs matched at HLA-A, -B, and -DRB1 loci, as shown by DNA typing. Among the 75 mismatched pairs, DNA typing of 63 pairs showed that 51 were mismatched at 1 HLA locus (18 HLA-A, 11 HLA-B, 22 HLA-DRB1) and 12 were mismatched at 2 or more loci. Seventeen patients (11%) experienced either early or late graft rejection. The incidence of grade III/IV acute graft versus host disease and chronic graft versus host disease was 20% (range, 7%-33%) and 30% (range, 12%-48%), respectively. Currently, 99 patients are alive, having survived for 3 to 82 months (median, 29 months) after their transplantations. The probability of overall survival at 5 years was 56% (95% confidence interval, 34%-78%). Multivariate analysis revealed the following unfavorable factors: transplantation more than 3 years after diagnosis (relative risk [RR], 1.86; P = .02), patients older than 20 years (RR, 2.27; P = .03), preconditioning regimen without antithymocyte globulin (RR 2.28; P = .04), and HLA-A or -B locus mismatching as determined by DNA typing. Matching of HLA class I alleles and improvement of preparative regimens should result in improved outcomes in patients with severe aplastic anemia who receive transplants from unrelated donors.

DNA Typing for HLA-A and HLA-B Identifies Disparities Between Patients and Unrelated Donors Matched by HLA-A and HLA-B Serology and HLA-DRB1

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 399-409 ◽  
Author(s):  
Vinod K. Prasad ◽  
Nancy A. Kernan ◽  
Glenn Heller ◽  
Richard J. O’Reilly ◽  
Soo Young Yang
Keyword(s):  
Bone Marrow ◽  
Graft Versus Host Disease ◽  
Graft Failure ◽  
Dna Typing ◽  
Outcome Studies ◽  
Cancer Center ◽  
Host Disease ◽  
Graft Versus Host ◽  
Related Variation ◽  
Unrelated Donors

Abstract High incidences of graft failure and graft-versus-host disease in the recipients of bone marrow transplantations (BMT) from unrelated donors (URD) may reflect the existence of allelic disparities between the patient and the URD despite apparent HLA identity at HLA-A, HLA-B, and HLA-DRB1 loci. To identify the extent and pattern of allelic disparities at HLA-A and HLA-B loci, 128 patients and 484 potential URD were evaluated by DNA typing. DNA typing for HLA-A, HLA-B, and HLA-DRB1 was performed at Memorial Sloan Kettering Cancer Center. HLA-A and HLA-B serotyping on URD was provided by the registries. By original typing (serology for HLA-A and HLA-B; DNA typing for DRB1) 187, 164, and 133 URD were 6/6, 5/6, and 4/6 matches, respectively. Following DNA typing, however, only 52.9% of the originally 6/6 matched URD remained 6/6, while 38.5%, 7.5%, and 1.1% were found to be 5/6, 4/6, and 3/6 matches. The level of disparity was higher in the originally 5/6 (P< .01) and 4/6 (P < .01) matched URD. A higher level of disparity was seen for HLA-B as compared to HLA-A. In addition, a serotype related variation was also noticed. For example, 24.1% of HLA-A2 and 60.1% of HLA-B35 seromatched URD were genotypically disparate, but no disparities were seen for HLA-A1 and HLA-B8. A higher percentage of HLA-A (67.4%) compared with HLA-B (35.4%) serologic homozygous URD remained genotypically homozygous (P = .01). The level of allelic disparity was lower (P < .01 for 6/6; P = .02 for 5/6) if the patient had one of the 15 most common haplotypes (A1B8DR3, A2B7DR15, A3B7DR15, etc) in comparison to the rest of the group. Outcome studies will answer the question whether these disparities are associated with a higher rate of immunological complications seen with URD-BMT.

scholarly journals Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 269-275 ◽  
Author(s):  
E Gluckman ◽  
MM Horowitz ◽  
RE Champlin ◽  
JM Hows ◽  
A Bacigalupo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Randomized Clinical Trials ◽  
Chronic Gvhd ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

Data for 595 patients with severe aplastic anemia receiving HLA- identical sibling bone marrow transplants were analyzed to determine the effect of pretransplant conditioning and graft-versus-host disease (GVHD) prophylaxis on outcome. Transplants were performed between 1980 and 1987 and reported to the International Bone Marrow Transplant Registry. Three conditioning regimens (cyclophosphamide alone, cyclophosphamide plus limited field radiation, and cyclophosphamide plus total body radiation) were studied; none was associated with superior long-term survival. Three GVHD prophylaxis regimens (methotrexate, cyclosporine, and methotrexate plus cyclosporine) were studied. Recipients of cyclosporine with or without methotrexate had a significantly higher probability of 5-year survival (69%, 95% confidence interval 63% to 74%) than patients receiving methotrexate only (56%, 49% to 62%, P less than .003). Higher survival with cyclosporine resulted from decreased risks of interstitial pneumonia (P less than .0002) and chronic GVHD (P less than .005). Additional risk factors adversely associated with survival included infection pretransplant (P less than .004), use of parous or transfused female donors (P less than .005), older patient age (P less than .005), and 20 or more pretransplant transfusions (P less than .006). These data may prove useful in planning randomized clinical trials and in identifying patients at high-risk of treatment failure.

scholarly journals Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 269-275 ◽  
Author(s):  
E Gluckman ◽  
MM Horowitz ◽  
RE Champlin ◽  
JM Hows ◽  
A Bacigalupo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Randomized Clinical Trials ◽  
Chronic Gvhd ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

Abstract Data for 595 patients with severe aplastic anemia receiving HLA- identical sibling bone marrow transplants were analyzed to determine the effect of pretransplant conditioning and graft-versus-host disease (GVHD) prophylaxis on outcome. Transplants were performed between 1980 and 1987 and reported to the International Bone Marrow Transplant Registry. Three conditioning regimens (cyclophosphamide alone, cyclophosphamide plus limited field radiation, and cyclophosphamide plus total body radiation) were studied; none was associated with superior long-term survival. Three GVHD prophylaxis regimens (methotrexate, cyclosporine, and methotrexate plus cyclosporine) were studied. Recipients of cyclosporine with or without methotrexate had a significantly higher probability of 5-year survival (69%, 95% confidence interval 63% to 74%) than patients receiving methotrexate only (56%, 49% to 62%, P less than .003). Higher survival with cyclosporine resulted from decreased risks of interstitial pneumonia (P less than .0002) and chronic GVHD (P less than .005). Additional risk factors adversely associated with survival included infection pretransplant (P less than .004), use of parous or transfused female donors (P less than .005), older patient age (P less than .005), and 20 or more pretransplant transfusions (P less than .006). These data may prove useful in planning randomized clinical trials and in identifying patients at high-risk of treatment failure.

scholarly journals Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia

Blood ◽  
2011 ◽  
Vol 118 (9) ◽  
pp. 2618-2621 ◽  
Author(s):  
Mary Eapen ◽  
Jennifer Le Rademacher ◽  
Joseph H. Antin ◽  
Richard E. Champlin ◽  
Jeanette Carreras ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Survival Rates ◽  
Human Leukocyte ◽  
Hazard Ratio ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Disease Risks

Abstract Outcome after unrelated donor bone marrow (BM) transplantation for severe aplastic anemia (SAA) has improved, with survival rates now approximately 75%. Increasing use of peripheral blood stem and progenitor cells (PBPCs) instead of BM as a graft source prompted us to compare outcomes of PBPC and BM transplantation for SAA. We studied 296 patients receiving either BM (n = 225) or PBPC (n = 71) from unrelated donors matched at human leukocyte antigen-A, -B, -C, -DRB1. Hematopoietic recovery was similar after PBPC and BM transplantation. Grade 2 to 4 acute graft-versus-host disease risks were higher after transplantation of PBPC compared with BM (hazard ratio = 1.68, P = .02; 48% vs 31%). Chronic graft-versus-host disease risks were not significantly different after adjusting for age at transplantation (hazard ratio = 1.39, P = .14). Mortality risks, independent of age, were higher after PBPC compared with BM transplantation (hazard ratio = 1.62, P = .04; 76% vs 61%). These data indicate that BM is the preferred graft source for unrelated donor transplantation in SAA.

scholarly journals Total lymphoid irradiation and cyclophosphamide as preparation for bone marrow transplantation in severe aplastic anemia

Blood ◽  
1980 ◽  
Vol 55 (2) ◽  
pp. 344-346 ◽  
Author(s):  
NK Ramsay ◽  
T Kim ◽  
ME Nesbit ◽  
W Krivit ◽  
PF Coccia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
New Combination ◽  
Severe Aplastic Anemia ◽  
Host Disease ◽  
Total Lymphoid Irradiation ◽  
Graft Versus Host

Abstract A new combination of total lymphoid irradiation and cyclophosphamide was used prior to bone marrow transplantation in an attempt to achieve decreased rejection rates and graft-versus-host disease. Nine previously transfused patients with severe aplastic anemia received marrow from an HLA-identical, MLC-compatible sibling following this preparative regimen. There were no episodes of graft rejection, and only one patient developed graft-versus-host disease. Of the 9 patients, 7 (78%) are surviving with a median follow-up of 400 days. The excellent results of this pretransplant combination of total lymphoid irradiation and cyclophosphamide warrants application of this regimen to a larger series of patients.

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