The Role of Anti-HLA Antibodies in Hematopoietic Stem Cell Transplantation

Focosi, Daniele; Zucca, Alessandra; Scatena, F.

doi:10.1016/j.bbmt.2011.06.004

Cited by 24 publications

(15 citation statements)

References 27 publications

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“…However, DSA, a phenomenon not encountered with fully HLAmatched donors, increases the risk of graft failure [10]. Additionally, DSA only detectable by highly sensitive immunoassays also significantly increases the risk of graft failure [12-16,24]. Although the adverse impact of DSA on alloBMT outcomes is well recognized, their overall incidence is unknown.…”

Section: Discussionmentioning

confidence: 99%

Partially Mismatched Transplantation and Human Leukocyte Antigen Donor-Specific Antibodies

Gladstone

Zachary

Fuchs

et al. 2013

Biology of Blood and Marrow Transplantation

110

113

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The presence of donor human leukocyte antigen (HLA)-specific antibodies (DSA) increases engraftment failure risk in partially HLA-mismatched, or HLA-haploidentical, allogeneic marrow(alloBMT) transplantation. As preexisting sensitization to HLA antigens is not well characterized among candidates for HLA-haploidentical alloBMT, we retrospectively evaluated both the incidence and relative strength of DSA in this patient population. Based on correlations of solid-phase antibody assays on the Luminex (Luminex, Austin, TX) platform with actual crossmatch tests, DSA were characterized as weak for results that were consistent with negative flow cytometric crossmatch results or as moderate-to-strong for results consistent with positive flow cytometric or cytotoxicity crossmatches. We evaluated 296 alloBMT candidates; 111 (37.5%) were female. DSA were detected in 43 (14.5%) candidates, mostly among female candidates (42.9% female versus 12.5% male). Moderate-to-strong DSA strength was more frequently encountered when directed against haploidentical donors as compared with mismatched unrelated donors. DSAwere most commonly detected in female patients directed against their children. Because the presence of DSA has been considered prohibitive for HLA-mismatched alloBMT, we additionally report a desensitization methodology used to reduce DSA to negative or weak levels, ie, levels well below those detectable in a flow cytometric crossmatch. Nine patients without other available donors underwent desensitization. Eight who reduced their DSA to negative or weak levels proceeded to alloBMT and achieved full donor engraftment. These data support routine DSA evaluation in all patients considered for mismatched alloBMT; however, for patients with no other viable options, desensitization to weak or negative DSA levels may afford the opportunity for successful transplantation.

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Section: Discussionmentioning

confidence: 99%

Partially Mismatched Transplantation and Human Leukocyte Antigen Donor-Specific Antibodies

Gladstone

Zachary

Fuchs

et al. 2013

Biology of Blood and Marrow Transplantation

110

113

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“…Similarly, Ciurea et al [41] found that DSHAs were associated with a high rate of graft rejection in patients undergoing haploidentical HSCT. On the basis of the previously mentioned findings, DSHA identification should be performed in HSCT settings where HLA matching is not complete [42]. Immunoadsorption and plasmapheresis could be considered to desensitize the recipient when no alternative donor is available.…”

Section: The Role Of Anti-hla Antibodiesmentioning

confidence: 99%

Role of HLA in Hematopoietic Stem Cell Transplantation

Park

Seo

2012

Bone Marrow Research

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The selection of hematopoietic stem cell transplantation (HSCT) donors includes a rigorous assessment of the availability and human leukocyte antigen (HLA) match status of donors. HLA plays a critical role in HSCT, but its involvement in HSCT is constantly in flux because of changing technologies and variations in clinical transplantation results. The increased availability of HSCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of killer-cell immunoglobulin-like receptor (KIR) genes in HSCT. The influence of nongenetic factors on the tolerability of HLA mismatching has recently become evident, demonstrating a need for the integration of both genetic and nongenetic variables in donor selection.

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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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The Role of Anti-HLA Antibodies in Hematopoietic Stem Cell Transplantation

Cited by 24 publications

References 27 publications

Partially Mismatched Transplantation and Human Leukocyte Antigen Donor-Specific Antibodies

Partially Mismatched Transplantation and Human Leukocyte Antigen Donor-Specific Antibodies

Role of HLA in Hematopoietic Stem Cell 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

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