ABSTRACT Haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) with post‐transplant cyclophosphamide (PTCy)‐based graft‐versus‐host disease (GVHD) prophylaxis is commonly used in patients without a fully matched donor. HLA evolutionary divergence (HED), a surrogate for the diversity of the immunopeptidome, can predict HLA‐matched HSCT outcomes. Because of the peculiarities of HED measurement in haplo‐HSCT, we designed a new HED D‐>R metric to proxy the fraction of the recipient‐specific immunopeptidome not recognised as self by the haplo‐identical donor, and evaluated its predictive value on haplo‐HSCT outcomes with the aim of providing help in choosing the best donor. We retrospectively studied 104 patients who underwent PTCy haplo‐HSCT for haematological malignancy and calculated per‐locus and per‐class HED in the recipient (HED R ), the donor (HED D ), across mismatched haplotypes (HED MM ) as well as HED D‐>R . Patients with low class 1 HED R had worse OS (hazard ratio (HR) 2.16, 95% confidence intervals (CI) 1.06–4.40, p = 0.033), whereas no significant impact of HED D or HED MM at any HLA locus was observed. Moreover, in multivariate analysis of patients surviving at least 100 days, low class 1 HED D‐>R was associated with inferior OS (HR 2.67, 95% CI 1.13–6.28; p = 0.025). In addition to strengthening the impact of recipient class 1 HED on HSCT outcomes regardless of donor type, our results suggest that our novel, publicly available, HED D‐>R metric could help select the most appropriate donor among haploidentical candidates.
Cordeiro et al. (Mon,) studied this question.