Hematopoietic Cell Transplantation from HLA Partially Matched Related Donors

Anasetti, Claudio; Velardi, Andrea

doi:10.1002/9780470987070.ch82

Cited by 23 publications

(27 citation statements)

References 109 publications

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“…4,6,10 This discrepancy may have been due to the difference in the method used for HLA matching. 1 The one-locus-mismatched group in the IBMTR study may have included a greater number of patients with another genotypic mismatch that could not be detected by serologic typing, compared to the Seattle study. However, in this study, we used genotypic matching, and thus it is very unlikely that patients in our one-locus-mismatched group in Figure 2C-D had another genotypic mismatch.…”

Section: Discussionmentioning

confidence: 99%

“…However, in most developed countries such donors are available for only approximately 30% of patients. 1,2 Therefore, hematopoietic stem cell transplants from family members other than HLA-matched siblings or unrelated volunteers has been investigated. The advantages of family members over unrelated donors are immediate availability and the ability to collect additional donor cells for immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…3,10 Therefore, some donor-recipient pairs that were considered to be mismatched for only one HLA locus in the IBMTR report might actually be more genetically disparate than those in the Seattle report. 1 Recently, molecular techniques have made it possible to identify HLA alleles that cannot be identified serologically (genomic typing). 11,12 Several groups have reported that a genotypic mismatch at DRB1 allele increased the risk of acute GVHD in HSCT from serologically HLA-matched unrelated donors.…”

Section: Introductionmentioning

confidence: 99%

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Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000)

Kanda

Chiba

Hirai

et al. 2003

Blood

141

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The reported outcome of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched family members has been inconsistent. The object of this study was to evaluate the true impact of HLAmismatch by using recent data from a homogenous population, excluding HSCT procedures that used graft manipulations, and by considering genotypic matching. Clinical data of 2947 patients who underwent allogeneic HSCT for leukemia or myelodysplastic syndrome were extracted from the database of the Japan Society for Hematopoietic Cell Transplantation. The main outcome measures were survival and the incidence of graft-versushost disease (GVHD). The presence of serologic HLA-mismatch, higher age, and high-risk disease were identified as independent risk factors for both shorter survival and the development of grade III to IV acute GVHD. The impact of HLAmismatch on survival was more relevant in standard-risk patients. These findings persisted when we used genotypic HLA matching. Survival after one-locusmismatched HSCT was equivalent to that after HLA-matched unrelated HSCT. We concluded that when a one-locusmismatched family donor is available for high-risk patients, immediate HSCT using this donor is warranted. In standard-risk patients, however, survival after onelocus-mismatched HSCT is significantly shorter than that after HLA-matched HSCT, and the indications for HSCT should be considered carefully. (Blood. 2003;102:1541-1547)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000)

Kanda

Chiba

Hirai

et al. 2003

Blood

141

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“…In a study of marrow transplantations from HLA-mismatched relatives, graft failure occurred in 13 of 21 patients (62%) with a positive pretransplantation cross-match (patient serum vs donor T or B lymphocytes), compared with 31 of 501 patients (7%) with a negative cross-match (P Ͻ .001). 5,6 Ottinger et al also found that a positive lymphocyte cross-match was a predictor for graft failure and poor survival after HCT from HLAmismatched donors. 7 Although a lymphocyte cross-match is an effective tool to evaluate alloimmunization and potential donor/recipient incompatibility, the procedure is labor intensive, may detect non-HLA antibodies, and is logistically difficult for remotely located unrelated donors because of the requirement for live cells.…”

Section: Introductionmentioning

confidence: 99%

The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure

Spellman

Bray

Rosen-Bronson

et al. 2010

Blood

Self Cite

255

179

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Donor-directed human leukocyte antigen (HLA)-specific allo-antibodies (DSAs) cause graft failure in animal models of hematopoietic stem cell transplantation (HCT). Archived pretransplantation sera from graft failure patients (n ‫؍‬ 37) and a matched case-control cohort (n ‫؍‬ 78) were tested to evaluate the role of DSAs in unrelated donor HCT. Controls were matched for disease, disease status, graft type, patient age, and transplantation year.Patients had acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome; 98% received myeloablative conditioning regimens 100% received T-replete grafts, 97% received marrow, 95% HLA-mismatched, and 97% received calcineurin-based graft-versus-host disease prophylaxis. Among the 37 failed transplantations, 9 (24%) recipients possessed DSAs against HLA-A, B, and/or DP, compared with only 1 (1%) of 78 controls. Therefore, the presence of DSAs was significantly associated with graft failure (odds ratio ‫؍‬ 22.84; 95% confidence interval, 3.57-ؕ; P < .001). These results indicate that the presence of pretransplantation DSAs in recipients of unrelated donor HCT is associated with failed engraftment and should be considered in HCT donor selection. (Blood. 2010; 115(13):2704-2708)

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“…The preference is based on the theory that HLA molecules that are more similar (belong to a crossreactive group or CREG) might be less immunogenic, a theory supported by a few small studies. 20 However, a current large study suggests that there is no difference in outcome between CREG-matched but antigen-mismatched donors and CREG-mismatched donors. 21 Second, these mismatched donors might be potentially mistyped and may actually carry the same antigen as the patient.…”

Section: Crossreactive Antigensmentioning

confidence: 96%

Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships

Hurley

Setterholm

Lau³

et al. 2003

Bone Marrow Transplant

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Summary:Registries and cord blood banks around the world collect and store the HLA types of volunteers in order to identify matched unrelated donors for patients requiring hematopoietic stem cell transplantation. This task is complicated by the many formats in which HLA types are provided by the testing laboratories (types obtained by serology vs by DNA-based methods; high vs intermediate vs low resolution) and by the need to identify which of these diverse types are most likely to match the HLA assignments of a searching patient as closely as possible. Conversion of the assignments to 'search determinants' may be included within the algorithm used to select and prioritize a list of potentially suitable donors, either as an aid to matching or as a tool to optimize the performance of comparisons within large data files. The strategies used by registries to create search determinants are described. A set of search determinants, utilized by the National Marrow Donor Program, is provided as an example and is intended to initiate further discussion aimed at understanding the process used by each registry with the possibility of developing a standard process among registries worldwide. (Table 1). As the complexity of HLA nomenclature increases 1 and as registries seek to exchange information to facilitate the world-wide search for unrelated donors, 2-4 it becomes critically important to clarify and perhaps even standardize the types of HLA assignments that are accepted into a registry, how assignments are compared, and how potential donors are identified within each registry. This document provides guidelines and suggests strategies for comparing the HLA assignments in order to identify potentially matched donors for a specific patient. Issues involving the limitations in the approaches used to interpret primary typing data obtained from DNA assays and the complications that this creates for registries have already been discussed. 5-8 HLA assignments for donors and patientsUsually, HLA-A, -B, and -DR types are assigned for volunteer donors and patients seeking an unrelated donor, and search algorithms are based on matching only for these

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Hematopoietic Cell Transplantation from HLA Partially Matched Related Donors

Cited by 23 publications

References 109 publications

Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000)

Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000)

The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure

Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships

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