scholarly journals HLA-Matched Sibling Transplantation for Severe Aplastic Anemia: Impact of HLA DR15 Antigen Status on Engraftment, Graft-versus-Host Disease, and Overall Survival

2012 ◽  
Vol 18 (9) ◽  
pp. 1401-1406 ◽  
Author(s):  
Minoo Battiwalla ◽  
Tao Wang ◽  
Jeanette Carreras ◽  
H. Joachim Deeg ◽  
Mouhab Ayas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Severe Aplastic Anemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Matched Sibling

The Presence of HLA DR15 Antigen in Patients with Severe Aplastic Anemia Does Not Impact Engraftment and Survival After HLA-Identical Sibling Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2280-2280
Author(s):  
Minoo Battiwalla ◽  
Tao Wang ◽  
Jeanette Carreras ◽  
H. Joachim Deeg ◽  
Mouhab F. Ayas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aplastic Anemia ◽  
Progenitor Cells ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Hla Typing ◽  
Severe Aplastic Anemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Peripheral Blood Progenitor Cells

Abstract Abstract 2280 Poster Board II-257 The HLA Class II antigen DR15 (common alleles 1501, 1502) is of interest in the pathobiology of T-lymphocyte mediated marrow failure (myelodysplastic syndrome (MDS), severe aplastic anemia (SAA) and paroxysmal nocturnal hemoglobinuria (PNH). Available data suggest that the presence of DR15 in patients with MDS is associated with an increased response rate to immunosuppressive therapy (IST) with ATG. While DR15 is overrepresented in patients with SAA and PNH, its presence has not been clearly shown to correlate with outcome after hematopoietic stem cell transplant in these diseases. We studied 1422 patients with SAA (30% were DR15+) who received HLA-identical sibling bone marrow (85%) or peripheral blood progenitor cells (15%) and were transplanted in 1990 – 2006 to determine whether the presence of HLA DR15 affected hematopoietic recovery, graft-versus-host disease or overall survival. The study was confined to matched sibling transplants to eliminate HLA-disparity as a driving force for any observed differences. High resolution HLA typing to discriminate between DR15 and DR16, the serological splits of DR2 was available for all subjects. Most patients (80%) had idiopathic SAA and 50% of patients were Caucasian. Patient, disease and transplant characteristics of patients with and without DR15 were similar. Proportions of patients who had received prior IST were similar among those with and without DR15. In multivariate analysis, after adjustment for significant factors, neutrophil recovery at day 28 (odds ratio [OR] 1.02, p=0.905), platelet recovery at day 100 (OR 0.95, p=0.776), secondary graft failure at 2 years (OR 0.66, p=0.123), acute (hazard ratio [HR] 0.88, p=0.345) and chronic (HR 1.09, p=0.519) graft-versus-host disease and overall mortality (HR 1.22, p=0.102) risks were similar in patients with and without DR15. Factors associated with higher mortality after transplantation included aracteristics as reported previously, including age older than 40 years (HR 2.74, p<0.001), poor performance score at transplantation (HR 1.72, p<0.001), non-Caucasians (HR 1.40, p=0.005), transplantation of peripheral blood progenitor cells (HR 1.43, p=0.019), transplantations before 2001 (HR 1.45, p=0.006) and conditioning regimens with cyclophosphamide alone (HR 1.44, p=0.022), cyclophosphamide with busulfan (HR 1.71, p=0.001) and fludarabine with other agents (HR 2.19, p<0.001). Agents used with fludarabine were: cyclophosphamide (n=54), busulfan (n=32) and monoclonocal antibody or irradiation (n=14). The 5-year probabilities of overall survival (after adjusting for the above factors that had an adverse effect on survival) were 79% in patients who were DR15 negative compared to 75% in those who were DR15+. Based on the sample size and a type I error rate of 5%, the probability of detecting a 5% difference in overall survival between the groups is 70% and a 10% difference, 98%. In conclusion, the presence of DR15 did not impact clinical outcomes after HLA-identical sibling transplantation for severe aplastic anemia. Disclosures: No relevant conflicts of interest to declare.

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.

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.

Transplant Outcome of Pediatric and Young Adult Patients with Aplastic Anemia: St Jude Children’s Research Hospital Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1210-1210
Author(s):  
Hesham Eissa ◽  
Brandon M. Triplett ◽  
Mari H Dallas ◽  
Ashok Srinivasan ◽  
Christine Hartford ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aplastic Anemia ◽  
Graft Versus Host Disease ◽  
Patient Population ◽  
Unrelated Donor ◽  
Recent Experience ◽  
Host Disease ◽  
Research Hospital ◽  
Graft Versus Host ◽  
Significant Difference

Abstract Background: Bone marrow transplant (BMT) remains the preferred frontline curative modality for patients with aplastic anemia in the presence of a matched sibling donor (MSD). In the absence of MSD the general consensus is frontline immunosuppressive therapy (IST) followed by BMT from a matched unrelated donor (MUD) in case of failure or relapse. No randomized controlled studies have been performed to compare earlier MUD transplant to 2nd cycle IST in case of failure of response to 1st IST cycle. In the pediatric population a higher percentage of congenital marrow failure syndromes is encountered than in adult world; the diagnosis of many of those is challenging clinically and from the molecular and genetic standpoints. Objectives: Review the outcome of 25 patients younger than 20 years diagnosed with aplastic anemia and recently transplanted at our institution. Compare outcomes of MSD versus MUD versus umbilical cord (UC) BMT in this patient population. Methods: A retrospective analysis was performed on 25 patients diagnosed with aplastic anemia who underwent BMT at St Jude Children’s Research Hospital between 9/1/2009 through 8/31/2013. Initial diagnosis and treatment, patients’ characteristics, transplant data, overall survival, and complications were analyzed. Results: Of the 25 patients reviewed, 15 patients were diagnosed with acquired aplastic anemia and 10 with congenital marrow failure, including 7 with dyskeratosis congenita (DKC), 1 with Shwachman Diamond syndrome (SDS), and 2 with congenital marrow failure not otherwise specified (negative genetic testing, but age, family history, and presentation consistent with congenital marrow failure). All 7 DKC patients had telomere lengths less than first percentile, and 2 had documented genetic mutations; of the 7 patients 2 received MSD, 3 received MUD and 2 received UC transplants. Most donors were MUD (13/25), 2 were UC donors as there were no other available donors, and 10 were MSD. All MSD recipients are alive, engrafted and disease free. There were 3 deaths. One MUD recipient with acquired aplastic anemia died of uncontrolled sepsis. Both UC recipients died; one had failure of engraftment and later died of acute myeloid leukemia that had developed on day +224 of transplant while on Danazol and G-CSF, and the other died of pulmonary and hepatic failure. The latter was the only patient who received TBI (2 Gy) as part of his conditioning regimen, engrafted on day +27 and died on day +33. There was no statistical difference in overall survival (OS) between MSD and MUD transplant (100% vs 92.3% at 3 years, respectively, p value = 0.38). Acute graft versus host disease (aGVHD) developed in 5 patients; 3 had received MUD transplant and 2 had received MSD. Two of these 5 patients also developed chronic graft versus host disease (cGVHD), which was limited in both cases. There was no statistically significant difference in engraftment or GVHD occurrence between the MSD and MUD patients. Conclusions: In our recent experience aplastic anemia in children,outcomes from MUD BMT were comparable to MSD BMT, especially with improved supportive care and GVHD prevention and treatment. Cord blood as an alternative donor source remains very challenging in this patient population from the engraftment and toxicity standpoints especially in certain congenital marrow failure syndromes. These data suggest that BMT should be considered earlier when there is MUD availability for patients with aplastic anemia. Figure 1 Figure 1. P unrelated vs cord = 0.0007 P sibling vs cord = 0.0002 P unrelated vs sibling = 0.38 Disclosures Reiss: Alexion Pharm: Research Funding.

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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