Acceptable HLA-mismatching in unrelated donor bone marrow transplantation for patients with acquired severe aplastic anemia

Yagasaki, Hiroshi; Kojima, Seiji; Yabe, Hiromasa; Katô, Kôji; Kigasawa, Hisato; Sakamaki, Hisashi; Tsuchida, Masahiro; Kato, Shingo; Kawase, Takakazu; Morishima, Yasuo; Kodera, Yoshihisa

doi:10.1182/blood-2011-04-349316

Cited by 48 publications

(32 citation statements)

References 22 publications

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“…[31][32][33] Clinical risk factors in the present study agree with those reported previously, including procedures for GVHD prophylaxis, intensity of the conditioning regimen, 34 disease, 35,36 leukemia relapse risk, and stem cell source. 37 It will be interesting to determine whether these candidates shift the HLA barrier quantitatively and maintain the same divergent effect of each HLA locus, or qualitatively alter the HLA locus-specific barrier.…”

Section: Discussionsupporting

confidence: 90%

Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

Morishima

Kashiwase

Matsuo

et al. 2015

Blood

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148

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Key Points• Significant HLA locus mismatches responsible for transplant-related events were determined in 7898 unrelated marrow donor transplants.• This information provides a rationale for use of an algorithm for unrelated donor selection.We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versusleukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection. (Blood. 2015;125(7):1189-1197

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Section: Discussionsupporting

confidence: 90%

Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

Morishima

Kashiwase

Matsuo

et al. 2015

Blood

Self Cite

148

120

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“…6 The effect of HLA mismatching, however, has not been well characterized in transplantation for nonmalignant diseases (NMD). Although its influence in severe aplastic anemia (SAA) has been reported in smaller studies, [7][8][9] little is known in other NMD.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders

Horan

Wang

Haagenson

et al. 2012

Blood

116

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“…However, although the age limit for this procedure, the timing of UD allo-HSCT and the impact of HLA mismatch have been tested as singular factors, the combined effect of these variables during the natural history of the disease remains unclear. 3,5,10 We, therefore, analyzed all patients who received an initial allo-HSCT for idiopathic SAA in France from a UD between 2000 and 2012, with the particular aim of evaluating the predictive value of the combination of age, timing of allo-HSCT and HLA matching on overall survival (OS) after UD allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party

et al. 2016

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U nrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.

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Acceptable HLA-mismatching in unrelated donor bone marrow transplantation for patients with acquired severe aplastic anemia

Cited by 48 publications

References 22 publications

Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party

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