HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection

Stevens, Cladd E.; Carrier, Carmelita; Carpenter, Carol; Sung, Dorothy; Scaradavou, Andromachi

doi:10.1182/blood-2010-11-317271

Cited by 55 publications

(45 citation statements)

References 44 publications

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“…The HLA mismatch direction also did not have an impact on overall survival. A similar finding regarding GVHD incidence was reported from the New York Blood Center [41].…”

Section: Impact Of Hla Mismatch Directionsupporting

confidence: 74%

Effect of HLA mismatch on acute graft-versus-host disease

Kanda

2013

Int J Hematol

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HLA matching between donors and recipients is the most important factor associated with acute graftversus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

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“…The HLA mismatch direction also did not have an impact on overall survival. A similar finding regarding GVHD incidence was reported from the New York Blood Center [41].…”

Section: Impact Of Hla Mismatch Directionsupporting

confidence: 74%

Effect of HLA mismatch on acute graft-versus-host disease

Kanda

2013

Int J Hematol

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“…The IPA effect on relapse was independent of other HLA associations, including donor-recipient HLA mismatch level, mismatch direction (vector), and matching for NIMA (13,18,19). One might expect that maternal exposure to IPAs in previous pregnancies might also contribute to controlling relapse through sensitization to other IPAs or a booster effect with repeated pregnancies.…”

Section: Discussionmentioning

confidence: 94%

Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation

Rood

Scaradavou

Stevens

2012

Proc. Natl. Acad. Sci. U.S.A.

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During pregnancy women can develop B-and T-cell immunity against the inherited paternal antigens (IPAs) of the fetus, such as HLA, peptides of minor histocompatibilty antigens, and possibly oncofetal antigens. The biological and pathological role of these pregnancy-induced immunological events is only understood in part. However, anti-IPA immunity in the mother persists for many decades after delivery and may reduce relapse in offspring with leukemia after HLA-haploidentical transplantation of maternal hematopoietic stem cells (HSC). We hypothesized that maternal anti-IPA immune elements cross the placenta and might confer a potent graft-versusleukemia effect when cord blood (CB) is used in unrelated HSC transplantation. In a retrospective study of single-unit CB recipients with all grafts provided by the New York Blood Center, we show that patients with acute myeloid or lymphoblastic leukemia (n = 845) who shared one or more HLA-A, -B, or -DRB1 antigens with their CB donor's IPAs had a significant decrease in leukemic relapse posttransplantation [hazard ratio (HR) = 0.38, P < 0.001] compared with those that did not. Remarkably, relapse reduction in patients receiving CB with one HLA mismatch (HR = 0.15, P < 0.001) was not associated with an increased risk of severe acute graft-versus-host disease (HR = 1.43, P = 0.730). Our findings may explain the unexpected low relapse rate after CB transplantation, open new avenues in the study of leukemic relapse after HSC transplantation (possibly of malignancies in general), and have practical implications for CB unit selection.cord blood stem cell transplantation | birth order

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“…10,31 Although standard myeloablative conditioning is usually sufficient to suppress donor-reactive host T cells and permits donor cell engraftment, RIC leaves larger numbers of residual host immunocompetent cells than myeloablative conditioning. However, the impacts of RIC on the kinetics of host T cells in the context of graft rejection have not been well delineated.…”

Section: Graft Rejection Is Mediated By Infusion Of Insufficient Numbmentioning

confidence: 99%

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning

Koyama

Hashimoto

Nagafuji

et al. 2013

Bone Marrow Transplant

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Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

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HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection

Cited by 55 publications

References 44 publications

Effect of HLA mismatch on acute graft-versus-host disease

Effect of HLA mismatch on acute graft-versus-host disease

Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning

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