The impact of HLA matching on outcomes of unmanipulated haploidentical HSCT is modulated by GVHD prophylaxis

Abstract

Key Points• In unmanipulated haplo-HSCT, antigenic HLA-DRB1 match, stem cell source, conditioning, and donor sex are associated with GVHD.• The role of HLAmatching status and other factors influencing alloreactivity is more prominent with PTCy compared to ATG GVHD prophylaxis.Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with unmanipulated grafts is increasingly adopted for high-risk acute leukemia, with acute graft-versus-host Moreover, the hazards of aGVHD were significantly associated with other factors influencing alloreactivity, including peripheral blood as stem cell source (HR, 2.2; 95% CI, 1.4-3; P , .01), reduced-intensity conditioning (HR, 0.6; 95% CI, 0.4-0.9; P 5 .04), and female donors (HR, 1.8; 95% CI, 1-3.2; P 5 .05), in PTCy but not ATG regimens. No significant associations were found between cumulative number of HLA mismatches and GVHD, or between HLA-matching status and other study end points including transplant-related mortality, disease-free survival, and relapse. Based on these data, the role of HLA mismatching on unshared haplotype appears not to be sufficiently prominent to justify its consideration in haploidentical donor selection. However, the role of HLA matching in haploidentical HSCT might be modulated by GVHD prophylaxis, calling for further investigations in this increasingly relevant field.

Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables

“…To date, there are no published reports of HLA disparity affecting transplant outcomes in T cell-replete haplo HSCT. To the contrary, multiple reports have suggested no impact of HLA disparity after either PTCy-or ATG-based haplo HSCT [11][12][13][14]. To this point our data confirm the lack of association between the number of HLA-A, -B, -C, -DRB1, and -DQB1 allelic mismatches and survival, given its opposing effects on relapse protection and worsening NRM.…”

“…On the contrary, the survival benefit afforded by an HLA-DR mismatch appears to be mostly due to improvement in NRM. Although the mechanism of this effect is unclear and deserves further study, a similar trend was noted by Lorentino et al [12] where the presence of HLA-DR allelic mismatch was associated with a nonsignificant trend to lower NRM (HR, .60; 95% confidence interval, .30 to 1.2; P = .13) in multivariate analysis. Although the group from Johns Hopkins University has shown a similar protective effect of HLA-DR disparity on survival, that effect was mostly due to relapse protection [11].…”

“…In contrast to the paramount importance of HLA matching on UD HSCT, the degree of HLA disparity has been reported to have no effect on transplant outcome in T cell-replete haplo HSCT, after either PTCy-or antithymocyte globulin (ATG)based approaches [11][12][13][14]. On the other hand, the presence of clinically significant DSA in the recipient, directed against donor HLA, appears to be similarly detrimental in haplo HSCT [15,16], and all efforts are usually made to avoid these donors.…”

Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide

“…However, modern transplant approaches [23], such as the use of post-transplantation cyclophosphamide (PTCy), have reduced the historically high rates of GVHD and NRM, making the safety and outcomes of HLA-haploidentical (haplo-) BMT now comparable with HLA-matched BMT [24–35]. In fact, earlier reports by our group and others found no significant association of the number of HLA mismatches between recipient and donor with either grades II to IV aGVHD or event-free survival after haplo-BMT with PTCy [36,37], but other potential risk factors for GVHD after haplo-BMT with PTCy have not been well defined.…”

Impact of cumulative steroid dose on infectious diseases after allogenic hematopoietic stem cell transplantation

“…[1][2][3] The use of systemic steroid along with the occurrence of GVHD has been suggested to be a risk factor for various infectious diseases, [4][5][6][7][8] which are main causes of transplant-related mortality. Since the number of HSCTs with a higher risk of complications, such as cord blood transplantations (CBT) and HLA mismatch transplantations in older patients, has been increasing, [9][10][11][12] it is important to evaluate the effect of steroid use on clinical outcomes.…”