Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome

Flomenberg, Neal; Baxter‐Lowe, Lee Ann; Confer, Dennis L.; Fernández-Viña, Marcelo; Filipovich, Alexandra H.; Horowitz, Mary M.; Hurley, Carolyn Katovich; Kollman, Craig; Anasetti, Claudio; Noreen, Harriet; Begovich, Ann B.; Hildebrand, William H.; Petersdorf, Effie W.; Schmeckpeper, Barbara J.; Setterholm, Michelle; Trachtenberg, Elizabeth; Williams, Thomas M.; Yunis, Edmond J.; Weisdorf, Daniel J.

doi:10.1182/blood-2004-03-0803

Cited by 630 publications

(541 citation statements)

References 53 publications

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“…We did not find any difference in outcomes between 10/10-HLA MUD versus DQB1-MMUD transplants whereas patients with non-DQB1 MMUD had a poorer OS than 10/10-HLA MUD. These results are consistent with previous reports [7,36]. However, this comparison might be prone to a lack of power, especially due to the small number of DQB1-MMUD transplants (n 5 18).…”

Section: Discussionsupporting

confidence: 92%

Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLA matched 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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Section: Discussionsupporting

confidence: 92%

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

et al. 2015

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“…Minor histocompatibility disparity in unrelated allogeneic transplantation may contribute to graft rejection and to graftversus-leukemia effects [38][39][40][41]. HLA class I mismatching including HLA-C and NK epitope mismatching are associated with higher rates of graft rejection and severe acute GVHD after unrelated donor transplantation [42,43]. Allele matching for adult unrelated blood and marrow grafting has improved rates of engraftment and GVHD.…”

Section: Ucb Basic Biology and Implications For Hematopoietic Reconstmentioning

confidence: 99%

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

Brown

Boussiotis

2008

Clinical Immunology

150

111

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Allogeneic stem cell transplantation has continued to evolve as a common procedure for the treatment of hematological malignancies and bone marrow failure. Donor bone marrow and mobilized peripheral stem cells are routinely employed for the reconstitution of immune function in leukemia and lymphoma patients following radiation and/or chemotherapy. Unfortunately, only 30% of patients have an HLA identical sibling donor and the identification of matched unrelated donors, particularly for minorities, can present an exceptional challenge. The transplantation of umbilical cord blood (UCB) represents the most recent strategy to expand the potential donor pool while maintaining an acceptable level of treatment related complications. First utilized in children, UCB transplantation permits a higher degree of HLA disparity while demonstrating a reduction in the incidence and severity of graft versus host disease (GvHD) compared to previous transplantation modalities. Despite the apparent decrease in GvHD, relapse rates remain comparable to transplantation with bone marrow or mobilized peripheral blood suggesting a strong graft versus leukemia/lymphoma (GvL) effect. However, several issues complicate the use of UCB transplantation and its extension to the treatment of adults. Many infections that afflict transplant patients are particularly frequent and more severe in the context of UCB transplantation. UCB T cells are naïve and therefore display less proliferation and IFN-γ production in response to cognate antigen and also appear to demonstrate defects in signal transduction mechanisms. In addition, UCB contain T regulatory cells (Treg) with more potent suppressor function than adult Treg. Furthermore, adult patients often require more total cells and CD34+ progenitors for transplantation than a single UCB unit can provide. Thus, strategies to expand selected subpopulations from UCB and the use of multiunit transplantation are areas of active research. This review will provide a condensed summary of the clinical history of UCB transplantation and emphasize the advantages and disadvantages of this approach to hematological malignancies in comparison to other methods of hematopoietic stem cell transplantation. Subsequently, it will mainly focus on the current challenges to immune reconstitution presented by UCB transplantation, recent research into their cellular and molecular mechanisms, and experimental approaches to overcome them.

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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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Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome

Cited by 630 publications

References 53 publications

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

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

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

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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