HLA evolutionary divergence score after donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation

Donor lymphocyte infusion (DLI) prevents acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapses following hematopoietic stem cell transplantation. Given the life-threatening toxicities such as graft versus host disease (GVHD), the identification of variables associated with response without toxicities is warranted. We hypothesized that HLA evolutionary divergence (HED), defined by the diversity between two given alleles of the same HLA gene, may be such a factor. A retrospective multicenter case-control study was conducted to evaluate the outcomes of pre-emptive (preDLI) and prophylactic DLI (proDLI) regarding their HED score, in AML or MDS patients. DLI-treated patients were matched with controls (1:2 matched) from French transplantation centers according to hospital, hemopathy, donor type, and risk classification. In total, 201 patients were included (N = 147 in the preDLI group, N = 54 in the proDLI group). Relapse-free survival was significantly better in the preDLI group (hazard ratio [HR] = 0.23, 95% confidence interval [CI]: 0.14–0.55, p < 0.001) than in controls. However, this benefit was offset by a higher incidence of severe GVHD (HR = 4.88, 95% CI: 2.30–10.32, p < 0.001). HED A, B, C, DQA1, DQB1, DPB1, and DRB1 were calculated for 65 DLI-treated patients. High-class II HED was significantly associated with higher GVHD and relapse-free survival (GRFS, HR = 0.33, 95% CI: 0.20–0.77, p = 0.005). Specific DQAB associations directly improved GRFS (HR = 0.23, 95% CI: 0.09–0.58, p = 0.004). In conclusion, screening the class II HED score identifies patients eligible for DLI treatment who will benefit the most from this strategy.