We have updated the catalogue of common and well-documented (CWD) HLA alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, and –DPB1 loci in IMGT/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and –DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being “common” (having known frequencies) and 707 as being “well-documented” on the basis of ~140,000 sequence-based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program’s bioinformatics web pages.
In multivariate analysis, DSAs were the only factor highly associated with graft failure (P ؍ .0001; odds ratio ؍ 21.3). Anti-HLA allosensitization was higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in women with 1 (P ؍ .008) and 2 or more pregnancies (P ؍ .0003) than in men. We conclude that the presence of anti-DPB1 DSAs is associated with graft failure in MUD hematopoietic stem cell transplantation. (Blood. 2011;118(22):5957-5964)
BACKGROUND
While donor-specific anti-HLA antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem cell transplantation (HSCT) remains unclear.
METHODS
To address the hypothesis that the presence of DSA contributes to the development graft failure, we tested 24 consecutive patients for the presence of anti-HLA antibodies determined by a highly sensitive and specific solid-phase/single-antigen assay. The study included a total of 28 haploidentical transplants, each with 2–5 HLA allele mismatches, at a single institution, from 9/2005 to 8/2008.
RESULTS
DSA were detected in five patients (21%). Three out of 4 (75%) patients with DSA prior to the first transplant failed to engraft, compared with 1 out of 20 (5%) without DSA (p=0.008). All 4 patients who experienced primary graft failure had second haploidentical transplants. One patient developed a second graft failure with persistent high DSA levels, while 3 engrafted, 2 of them in the absence of DSA. No other known factors that could negatively influence engraftment were associated with the development of graft failure in these patients.
CONCLUSIONS
These results suggest that donor-specific anti-HLA antibodies are associated with a high rate of graft rejection in patients undergoing haploidentical stem cell transplantation. Anti-HLA sensitization should be evaluated routinely in hematopoietic stem cell transplantation with HLA mismatched donors.
Hematopoietic stem cell transplantation from unrelated donors is an effective treatment for myeloid malignancies, but its use is usually restricted to young patients without comorbidities. The development of reduced-intensity preparative regimens has allowed the extension of this form of treatment to older and medically infirm patients. We assessed the outcomes of patients older than 54 years who received unrelated donor transplants for the treatment of myeloid malignancies in our institution. There were 29 patients (median age, 59 years) with advanced acute myeloid leukemia (n ؍ 13), myelodysplastic syndrome (n ؍ 7), and chronic myeloid leukemia (n ؍ 9) included. With a median follow-up of 27 months, the probability of overall and event-free survival, and nonrelapse mortality at one year were 44%, 37%, and 55%, respectively. Grades II to IV acute graft-versus-host disease (GVHD) occurred in 41% of patients and chronic GVHD developed in 63% of patients surviving more than 100 days. Of the 11 survivors, 9 were interviewed and
Key Points
Three or more mismatches at the Low Expression Loci may adversely affect clinical outcome after 7/8 matched transplantation. Match grade at the Low Expression HLA Loci may be considered to select 7/8 donors with potentially lower posttransplant risks.
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