Human Leukocyte Antigen Mismatching and Survival in Contemporary Hematopoietic Cell Transplantation for Hematologic Malignancies
Menées à partir de données 2016-2020 portant sur 17 292 patients atteints d'une leucémie aiguë ou d'une tumeur myéloïde et ayant reçu une greffe de cellules souches hématopoïétiques issues d'un donneur non apparenté avec une incompatibilité sur un gène HLA (dont 1 523 ayant reçu du cyclophosphamide post-greffe pour prévenir une maladie du greffon contre l'hôte), ces études analysent l'association entre la non-concordance de classe I ou de classe II des gène HLA du donneur et du receveur et la survie globale des patients
PURPOSE: Human leukocyte antigen (HLA) mismatching can reduce survival of patients with blood cancer after hematopoietic cell transplantation (HCT). How recent advances in HCT practice, in particular graft-versus-host disease (GVHD) prophylaxis by post-transplantation cyclophosphamide (PTCy), influence HLA risk associations is unknown. PATIENTS AND METHODS: The study included 17,292 unrelated HCTs with 6-locus high-resolution HLA typing, performed mainly for acute leukemia or related myeloid neoplasms between 2016 and 2020, including 1,523 transplants with PTCy. HLA risk associations were evaluated by multivariable Cox regression models, with overall survival (OS) as primary end point. RESULTS: OS was lower in HLA mismatched compared with fully matched transplants (hazard ratio [HR], 1.23 [99% CI, 1.14 to 1.33]; P < .001). This was driven by class I HLA-A, HLA-B, HLA-C (HR, 1.29 [99% CI, 1.19 to 1.41]; P < .001) but not class II HLA-DRB1 and HLA-DQB1 (HR, 1.07 [99% CI, 0.93 to 1.23]; P = .19). Class I antigen-level mismatches were associated with worse OS than allele-level mismatches (HR, 1.36 [99% CI, 1.24 to 1.49]; P < .001), as were class I graft-versus-host peptide-binding motif (PBM) mismatches compared with matches (HR, 1.42 [99% CI, 1.28 to 1.59]; P < .001). The use of PTCy improved GVHD, relapse-free survival compared with conventional prophylaxis in HLA-matched transplants (HR, 0.77 [0.66 to 0.9]; P < .001). HLA mismatching increased mortality in PTCy transplants (HR, 1.32 [1.04 to 1.68]; P = .003) similarly as in non-PTCy transplants (interaction P = .43). CONCLUSION: Class I but not class II HLA mismatches, especially at the antigen and PBM level, are associated with inferior survival in contemporary unrelated HCT. These effects are not significantly different between non-PTCy compared with PTCy transplants. Optimized HLA matching should still be considered in modern HCT.