Impact of anti-HLA antibodies on allogeneic hematopoietic stem cell transplantation outcomes after reduced-intensity conditioning regimens

Detrait, Marie; Dubois, Valérie; Sobh, Mohamad; Morisset, Stéphane; Tedone, Nathalie; Labussière, Hélène; Gillis, Lilia; Barraco, Fiorenza; Cannas, Giovanna; Ducastelle, Sophie; Fatoum, Jihane; Thomas, Xavier; Chelgoum, Youcef; Nicolini, Franck‐Emmanuel; Michallet, Mauricette

doi:10.1016/j.exphem.2012.06.003

Cited by 28 publications

(16 citation statements)

References 26 publications

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“…Furthermore, clinical observations from two groups failed to find a correlation between presence of HLA Abs and graft failure. 8,10 This is in contrast with many other clinical observations that show a strong correlation. [1][2][3] Prospective studies of treatment interventions may over time contribute to elucidating the pathophysiological role of HLA Abs in this setting.…”

contrasting

confidence: 81%

“…Furthermore, others found persistence of HLA Abs beyond conditioning in approximately half of the patients that tested positive for HLA Abs before transplantation. 8 Gladstone et al 9 recently described a similar desensitization strategy in nine patients utilizing plasmapheresis, i.v. Ig, tacrolimus and mycophenolate mofetil starting 1-2 weeks before conditioning.…”

mentioning

confidence: 99%

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A strategy to reduce donor-specific HLA Abs before allogeneic transplantation

Gergis

Mayer

Gordon

et al. 2014

Bone Marrow Transplant

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contrasting

confidence: 81%

mentioning

confidence: 99%

A strategy to reduce donor-specific HLA Abs before allogeneic transplantation

Gergis

Mayer

Gordon

et al. 2014

Bone Marrow Transplant

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“…Besides factors such as age, sex, disease stage, conditioning regimen and degree of HLA identity that can affect the outcomes of allo-HSCT, anti-HLA antibodies, especially donor-specific anti-HLA antibodies (DSHAs), have been shown to have a negative prognostic impact in patients who undergo cord blood transplantation (CBT) [2], haploidentical SCT [3], and HLA-mismatched unrelated SCT [4]. Having anti-HLA antibodies or DSHAs have a negative effect on engraftment and contributes to a lower overall survival (OS) rate and higher graft failure [5][6][7]. The National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research (CIBMTR) provide guidelines in 2012, in which anti-HLA antibody and HLA-DP loci typing should be examined as a part of the pre-transplantation work-up for unrelated adult donor and cord blood graft selection [8].…”

Section: Introductionmentioning

confidence: 99%

Dynamic Detection of Anti–Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12–Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Pan

Yuan

et al. 2016

Biology of Blood and Marrow Transplantation

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The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP-mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)-matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. Anti-HLA antibodies using the Luminex method was applied to 123, 117, and 106 serum samples collected before and 1 month and 3 months after transplantation. The presences of anti-HLA antibodies at the 3 time points were 37.4% (46 of 123), 40.2% (47 of 117), and 22.6% (24 of 106). Mismatch of HLA-DPB1 and/or DPA1 allele between patient-donor pairs was 83.6% (92 of 110). Patients with anti-HLA antibodies had delayed platelet recovery. The presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic graft-versus-host disease (GVHD), higher treatment-related mortality, and reduced overall survival (OS) and disease-free survival, especially in acute myeloid leukemia and myelodysplastic syndrome patients. Multivariate analysis showed that presence of anti-HLA antibodies before transplantation was a risk factor for GVHD and OS. Furthermore, HLA-DP loci-matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT.

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“…Although recent registry data have suggested that the presence of pre-transplant DSAs is correlated with an increased risk for graft rejection, [17][18][19][20][21][22] other reports have shown no association between the presence of DSAs and engraftment. 23,24 In addition, strategies for prevention of Ab-mediated graft rejection, such as plasma exchange, platelet transfusion and rituximab, have been proposed, but their efficacy is limited. 25,26 Thus, it is unclear whether DSAs can actually mediate graft rejection or if they are simply surrogate markers for the cellular immunity that causes graft rejection.…”

Section: Introductionmentioning

confidence: 99%

Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection

Hanajiri

Murata

Sugimoto

et al. 2015

Bone Marrow Transplant

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In allo-stem cell transplantation (SCT), it is unclear whether donor-specific anti-HLA Abs (DSAs) can actually mediate graft rejection or if they are simply surrogate markers for the cellular immunity that causes graft rejection. Here, we first analyzed a case of cord blood allograft rejection in which DSA and cytotoxic T lymphocyte (CTL) specific for donor HLA-B*54:01 were detected at the time of graft rejection. Both the DSA and CTL inhibited colony formation by unrelated bone marrow mononuclear cells sharing HLA-B*54:01, suggesting that the humoral and cellular immune responses were involved in the graft rejection. Interestingly, the DSA and CTL were also detected in cryopreserved pre-transplant patient blood, raising a hypothesis that the presence of anti-HLA Abs could be an indicator for corresponding HLA-specific T cells. We then evaluated the existence of HLA-specific CD8 + T cells in other patient blood specimens having anti-HLA class I Abs. Interferon-γ enzyme-linked immunospot assays clearly confirmed the existence of corresponding HLA-specific T-cell precursors in three of seven patients with anti-HLA Abs. In conclusion, our data demonstrate that integrated humoral and cellular immunity recognizing the same alloantigen of the donor can mediate graft rejection in DSA-positive patients undergoing HLA-mismatched allo-SCT. Further studies generalizing our observation are warranted.

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Impact of anti-HLA antibodies on allogeneic hematopoietic stem cell transplantation outcomes after reduced-intensity conditioning regimens

Cited by 28 publications

References 26 publications

A strategy to reduce donor-specific HLA Abs before allogeneic transplantation

A strategy to reduce donor-specific HLA Abs before allogeneic transplantation

Dynamic Detection of Anti–Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12–Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection

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