Superior survival associated with transplantation of matched unrelated versus one-antigen–mismatched unrelated or highly human leukocyte antigen– disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts

Abstract

The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigenmismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning regimen and a graft-versus-host disease (GVHD) prophylaxis schedule with the exception of recipients of haploidentical marrow grafts, who received antithymocyte globulin after bone marrow transplantation as additional immunosuppression. There was no statistically significant difference in the rate of engraftment, or the cumulative incidences of acute and chronic GVHD between any of the 3 groups. The 2-year cumulative incidence of relapse was lower in matched unrelated patients (25%, P ‫؍‬ .01) and mismatched unrelated patients (26%, P ‫؍‬ .014) than in haploidentical patients (42%). Transplant-related mortality was significantly higher in recipients of mismatched unrelated grafts (45%, P ‫؍‬ .01) and haploidentical grafts (42%, P ‫؍‬ .001) compared with recipients of matched unrelated marrow grafts (23%). This resulted in a significantly higher probability of overall survival for matched unrelated patients (58%) versus either mismatched unrelated (34%, P ‫؍‬ .01) or haploidentical (21%, P ‫؍‬ .002) patients. There was no statistically significant difference in survival between patients who received mismatched unrelated grafts versus those who received haploidentical grafts. This study supports a donor selection algorithm whereby patients who lack a closely matched family donor be offered a phenotypically matched unrelated donor if available. There is no apparent advantage to using a mismatched unrelated versus a highly HLA-disparate family donor. (Blood. 2002;99:806-814)

Isolated HLA-C mismatches in unrelated donor transplantation for CML

“…If we put these results up against the most recent studies on CML patients of the Seattle group 11,14 that show a deleterious effect of borderline significance with single HLA-A, HLA-B or HLA-DRB1 mismatches, we might consider the risks associated with an isolated HLA-C MM to be possibly equal in size. However, if we compare our results with our previous work 9 or with that of recent work of others, 16,26,27 all showing a significant association of a single MM with an unfavorable outcome, we might consider an HLA-C MM as less relevant than HLA-A, HLA-B or HLA-DRB1 mismatches. We do favor the latter possibility because our results in an ongoing study on patients transplanted with stem cells from unrelated donors seem to confirm the trend found in this study with HLA-C mismatches being less hazardous than the clearly significant risk factors of single HLA-A, HLA-B or HLA-DRB1 mismatches.…”

Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies

“…1,3,12 Although T-cell depletion and high-dose infusions of CD34 þ cells reduced the incidence of severe GVHD and improved the rate of engraftment, frequency of relapse and infections remained high and the long-term survival was poor. 13,14 The reported studies involved small numbers of patients without long-term followup despite several encouraging reports.…”

“…However, this attempt, especially before the end of last decade, was associated poor engraftment, high risk of early death and severe graft-versus-host disease (GVHD). [1][2][3] The approach of T-cell depletion (TCD) or CD34 þ cell selection in vitro overcame the HLA barrier but was also confronted with delayed immune reconstitution. 4 Here, we describe a method for haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) from family members without in vitro TCD, which is designed to overcome HLA barriers and reduce complications.…”

Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias

“…In our study, we noted a higher overall NRM in recipients of PMRD compared to those of URD donors, but no difference in outcomes. In contrast, the study by Drobyski et al, 29 compared recipients of matched and mismatched URD and PMRD. Recipients of matched URD had a superior survival (58%) to either mismatched URD (34%) or haploidentical recipients (21%).…”