Abstract
HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA. We retrospectively scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II (PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease. These patients were divided into low and high PIRCHE-I and PIRCHE-II groups, based on their PIRCHE scores, and compared using multivariate statistical analysis methods. The high PIRCHE-II group had a significantly impaired OS compared to the low PIRCHE-II group and the 10/10 reference group (HR: 1.86, 95%-CI: 1.02–3.40; and HR: 2.65, 95%-CI: 1.53–4.60, respectively). Overall, PIRCHE-II seem to have a more prominent effect on OS than PIRCHE-I. This impaired OS is probably due to an increased risk for severe acute graft-vs.-host disease. These data suggest that high PIRCHE-II scores may be used to identify non-permissible HLA mismatches within single HLA-mismatched hematopoietic stem-cell transplantations.
Highlights
HLA mismatching is an important factor in the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT), leading to an impaired overall survival (OS) [1]
[Hazard Ratio (HR): 1.61, 95% confidence interval (95%-CI): 1.09–2.37, p = 0.02], whereas for the intermediate and late-stage disease patients no differences in OS were observed between 9/10-mismatched unrelated donor (MUD) and 10/10-MUD (Table 1)
Since our data confirm that the effect of HLA mismatching on OS is more prominent in early-stage disease patients, we investigated whether Predicted Indirectly ReCognizable HLA Epitopes” (PIRCHE) scores may aid to identify non-permissible HLA mismatches within this patient group
Summary
HLA mismatching is an important factor in the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT), leading to an impaired overall survival (OS) [1]. HLA-matched (10/10) unrelated donors are available for 23– 67% of the patients, depending on the ethnicity [4,5,6]. This underscores the urgent medical need, in the era of novel transplantation concepts, to discriminate between detrimental HLA mismatches (non-permissible) and well-tolerated HLA (permissible) mismatches. The PIRCHE model has shown correlations with transplant outcome in HLA-C and HLADPB1 mismatched unrelated donor (MUD) HSCT [8, 9], in HLA-mismatched cord blood transplantation [10], and with de novo HLA antibody formation in organ transplantation and pregnancy [11,12,13,14]. In the current retrospective explorative study we multivariately investigate the role of the PIRCHE algorithm in identifying non-permissible HLA mismatches in 9/10-matched HSCT transplantations
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