Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers?

Abstract

The aim of this study was to identify significant prognostic factors by using unrelated genomically HLA-A, -B and -DRB1-identical donors. Such data could help to choose the best donor. We studied 136 consecutive patients with hematologic malignancies and a median age of 32 years (range, 0-55 years) who received hematopoietic stem cell transplantation. Bone marrow grafts were given to 83 and peripheral blood stem cells to 53 patients. The cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 30% and of chronic GVHD was 54%. At 5 years, the overall transplant-related mortality (TRM) was 34%, and patient survival was 50%. In Cox multivariate analysis, 32 potential risk factors were analyzed. Monoclonal antibody OKT-3 during conditioning was correlated with grade II to IV acute GVHD, chronic GVHD, and TRM. HLA-DP mismatch was associated with poor TRM and poor survival. Cytomegalovirus-seropositive patients with a seronegative donor had a decreased leukemia-free survival. Five-year TRM was 14% with no risk factor, 38% with 1 risk factor, and 87% with 2 risk factors. The 5-year survival was 72%, 48%, and 30% with 0, 1, and 2 risk factors, respectively. We concluded that unrelated hematopoietic stem cell transplantation may be improved if an optimal donor and immunosuppression are chosen.

Strategies of the donor search for children with second CR ALL lacking a matched sibling donor

“…30 In another study, multivariate analysis showed that poor leukaemia-free survival is associated with CMV-seronegative grafts to CMV-seropositive recipients. 27 These results were not confirmed by a recent study that detected no adverse effects of donor and recipient CMV serology status on survival, GvHD, engraftment or relapse. 31 The preemptive use of drugs such as ganciclovir and CMV-specific T cells might contribute to preventing CMV infections in recipients who are at risk.…”

“…Conflicting results have been reported on the relative importance of various class I and II loci mismatches on outcome. [21][22][23][24][25][26][27][28] Early studies reported that low-resolution mismatches at HLA-A and -B Ags, and high-resolution mismatches at HLA-DRB1 allele are associated with worse GvHD and survival. [21][22] Matching algorithms favoured class II matching over class I matching when a complete match could not be found.…”

“…26 In this large study, a single HLA class I or II allele mismatch had no influence on survival, while multiple mismatching for more than one class I allele and simultaneous disparities in class I and II alleles increased the mortality rate. With regard to HLA-DP matching, Ringden et al 27 reported observing a positive impact on outcome. In fact, additional benefits may be reaped by matching HLA-DQB1 and -DPB1 in patients who have several highly matched suitable donors.…”

Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor

“…14 HLA typing for class I and class II was carried out by allele-level PCR amplification with sequence-specific primers. 5 Of the 27 UCB cases, 1 patient had an HLA-A, -B and -DRb1-matched donor, 1 got a two minor Ag-mismatched graft, 14 had one HLA-Ag mismatch (8 patients, in addition, had minor mismatches) and 12 had two HLA Ag mismatches out of which 6 in addition had minor mismatches ( Table 1). The MM URD grafts included one HLA-A mismatch in six patients, an HLA-B Ag mismatch in five, and a DRb1 Ag mismatch in three patients.…”

“…1,2 With improved genomic tissue typing, results using unrelated donors are very similar to those obtained using HLA-identical siblings. [3][4][5] Despite the fact that the volunteer registries now contain more than 12 million unrelated donors, the pool is not large enough to find an HLA-matched donor for all patients. Especially for those with rare HLA alleles, an alternative donor must be sought.…”