High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation

Lee, Stephanie J.; Klein, John P.; Haagenson, Michael; Baxter‐Lowe, Lee Ann; Confer, Dennis L.; Eapen, Mary; Fernández-Viña, Marcelo; Flomenberg, Neal; Horowitz, Mary M.; Hurley, Carolyn Katovich; Noreen, Harriet; Oudshoorn, Machteld; Petersdorf, Effie W.; Setterholm, Michelle; Spellman, Stephen R.; Weisdorf, Daniel J.; Williams, Thomas M.; Anasetti, Claudio

doi:10.1182/blood-2007-06-097386

Cited by 1,135 publications

(1,157 citation statements)

References 22 publications

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“…Disease status at time of transplantation was classified as early, intermediate, and advanced according to standard definitions [20]. Comorbidities were scored according to the HCT-specific comorbidity index, and severity was graded as low (score 0), intermediate (score [1][2], and high (score 3) as previously defined [21].…”

Section: Methodsmentioning

confidence: 99%

Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA‐identical sibling donor allogeneic hematopoietic cell transplantation

et al. 2014

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Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) despite current prophylaxis. Methotrexate (MTX) with a calcineurin inhibitor (CNI) is the current standard, however, has several toxicities. Mycophenolate mofetil (MMF) is frequently used in reduced-intensity HCT, but data in myeloablative transplants is limited. We thus retrospectively identified 241 patients who underwent myeloablative HCT from an HLA-identical sibling donor; 174 patients received cyclosporine (CSA) 1 MMF and 67 received CSA1MTX. Patients receiving MMF 1 CSA had rapid neutrophil (median 11 vs. 19 days with MTX1CSA), and platelet recovery (median 19 vs. 25 days), lower incidence of severe mucositis by OMAS (19% vs. 53%), and shorter length of hospital stay (median 25 vs. 36 days) (P < 0.001 for all comparisons). There were no significant differences in incidence of grade 2-4 (MMF1CSA 37% vs. MTX1CSA 39%) or 3-4 acute GVHD (17% vs. 12%), chronic GVHD (46% vs. 56%), relapse (28% vs. 27%), non-relapse mortality (20% vs. 27%), or overall survival (47% vs. 44%) (P 5 NS for all). However, in multivariable analysis, the use of MMF1CSA was associated with an increased risk of severe grade 3-4 acute GVHD (HR 2.92, 95% CI 1.2-7.15, P 5 0.019). There were no differences between the two regimens in multivariable analyses for other survival outcomes. This analysis demonstrates that the use of MMF in myeloablative sibling donor transplantation is well tolerated. However, there may be an increased risk of severe GVHD with MMF1CSA compared to MTX1CSA. Further studies evaluating optimal dosing strategies are needed.

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Section: Methodsmentioning

confidence: 99%

Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA‐identical sibling donor allogeneic hematopoietic cell transplantation

et al. 2014

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“…In comparison with transplants from adult donors, UCB transplants offer the advantage of prompt availability for many recipients and a decreased risk of graft-versus-host disease (GVHD) [2,3], but such transplants are associated with a slower hematological and immune recovery, leading to a higher risk of infection [4,5]. Mismatched-unrelated donor transplants are associated in some studies with a lower risk of relapse, but a higher risk of GVHD [6,7], while haploidentical HSCT may be complicated by a high risk of relapse and delayed immune recovery [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLAmatched donors and cord blood

et al. 2015

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In absence of available matched-related or unrelated donor (MUD), mismatched unrelated donors (MMUD) and unrelated cord blood (UCB) are both considered to be suitable donors, with similar post-transplant overall survival. In most of these retrospective comparisons, HLA typing of adult donors was performed at eight loci. The aim of this study was to compare the outcome of patients transplanted from UCB (N 5 64) with those transplanted from 9/10-HLA MMUD (N 5 84) or 10/10-HLA MUD (N 5 196). In multivariate analysis, UCB was associated with less Grade II-IV acute GVHD in comparison with MUD (aHR 1.97, 95% CI 1.19-3.27, P 5 0.009) and MMUD transplants (aHR 1.79, 95% CI 1.02-3.15, P 5 0.042), while the cumulative incidence of chronic GVHD was not significantly different between the three groups. Overall survival (OS), non-relapse mortality, and relapse were not different between MMUD and UCB transplantation, whereas OS was impaired after UCB in comparison with MUD (aHR 0.65, 95% CI 0.43-0.99, P 5 0.043). Factors also impacting OS were the donor/recipient CMV serostatus (Donor2/Recipient1 aHR 1.76, 95% CI 1.23-2.52, P 5 0.002 compared with D2/R2), the donor/recipient gender combination (Female/Male versus other combinations aHR 1.57, 95% CI 1.11-2.22, P 5 0.012) and disease risk (aHR 1.58, 95% CI 1.05-2.38, P 5 0.027 for high vs. low risk disease). Our data confirm that UCB and 9/10-HLA MMUD are both relevant alternative options when no 10/10-HLA donor is available. Donor/recipient gender combination and CMV serostatus had a significant impact on survival and may be taken into account, along with donor type, in the setting of MMUD and UCB transplants.

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“…Several retrospective studies have demonstrated that the presence of HLA allele mismatch was associated with an increased risk of graft-versus-host disease (GVHD) in unrelated HSCT [3][4][5][6]. Although the disparity of HLA molecules in HLA antigen mismatch is greater than that in HLA allele mismatch without HLA antigen mismatch, the impact of HLA mismatch on the clinical outcome for antigen mismatch was considered to be, for practical purposes, similar to that for allele mismatch, as reported previously in the setting of unrelated HSCT [4,7,8]. Although the impact of an HLA mismatch at each locus varied among the studies, there is a consensus that an HLA mismatch at any locus, including A, B, C and DRB1, is in general associated with a poor clinical outcome [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 89%

A single high‐resolution HLA mismatch has a similar adverse impact on the outcome of related hematopoietic stem cell transplantation as a single low‐resolution HLA mismatch

Fuji¹,

Kanda

Kato

et al. 2015

American J Hematol

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The relative importance of the resolution level of HLA typing has not been fully defined for related donor transplantation. To address this question, we retrospectively evaluated patients who underwent a first related hematopoietic stem cell transplantation (HSCT) from 2000 to 2011 from an HLA high‐resolution matched (MRD, n = 2,244), high‐resolution 1 locus‐mismatched (HR‐MMRD, n = 116), or low‐resolution 1 locus‐mismatched related donor (LR‐MMRD, n = 396) in the graft‐versus‐host direction at three loci (HLA A, B, and DRB1) using the database of the Japan Society for Hematopoietic Cell Transplantation. The median age was 40 years (0–74). The median follow‐up duration of surviving patients was 950 days. Although the cumulative incidences of grade III–IV acute graft‐versus‐host disease (GVHD) in the HR‐MMRD and LR‐MMRD groups were significantly higher than those in the MRD group (HR‐MMRD 19.8%, LR‐MMRD 20.4%, and MRD 9.5%), there was no statistically significant difference between the HR‐MMRD and LR‐MMRD groups (P = 0.65). Although both HR‐MMRD and LR‐MMRD were significantly associated with an increased risk of non‐relapse mortality and a worse overall survival, there was no statistically significant difference between the HR‐MMRD and LR‐MMRD groups. In conclusion, LR‐MM and HR‐MM have a similar adverse impact on the outcome in related HSCT. Am. J. Hematol. 90:618–623, 2015. © 2015 Wiley Periodicals, Inc.

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High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation

Cited by 1,135 publications

References 22 publications

Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA‐identical sibling donor allogeneic hematopoietic cell transplantation

Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA‐identical sibling donor allogeneic hematopoietic cell transplantation

Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLAmatched donors and cord blood

A single high‐resolution HLA mismatch has a similar adverse impact on the outcome of related hematopoietic stem cell transplantation as a single low‐resolution HLA mismatch

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