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Introduction: Unrelated Cord Blood Transplantation (UCBT) provides a curative therapy for patients with hematological malignancies (and a variety of benign disorders). HLA-mismatched UCBT is associated with improved leukemia control. The aim of this study was to investigate whether indirect recognition of the mismatched HLA provides an explanation for this improved graft-versus-leukemia (GVL) effect, and can be used to identify donors with optimal GVL properties without impacting probability on graft-versus-host disease (GVHD).
Methods: All consecutive pediatric patients transplanted from 2004 for various diseases after myeloablative conditioning (either Busulfan-based or TBI-based), with an UCBT were included. The probability of indirect recognition was predicted by determining the number of Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE), as described previously (K. A. Thus, et al., BBMT 2014). Patients were divided into two groups, according to the numbers of PIRCHE presented by HLA class I and II (PIRCHE-I and –II, respectively), above and at or below median number of PIRCHE. Primary endpoint: relapse. Secondary endpoints: acute- and chronic GVHD, disease-free survival (DFS), and transplant-related mortality (TRM). Cox proportional hazard models were used for analyses.
Results: 156 patients, median age 5 (range 0-22) years, were included; 50 for a malignancy; 22 AML, 22 ALL, and 6 other. 127 (81%) patients received Bu-based and 29 (19%) TBI-based conditioning. In multivariate analyses, above median number PIRCHE-I were associated with lower probability of relapse (HR 0.139, p=0.006, Fig 1), and a trend for improved disease-free survival (HR 0.411, p=0.086). This effect was not present for PIRCHE-II. In the whole cohort, PIRCHE-I or –II were neither associated with acute-GVHD grade II-IV (HR 0.747, p=0.466, HR 1.263, p=0.554) nor extensive chronic GVHD (HR 1.502, p=0.671, HR 3.420, p=0.293), nor TRM (HR 1.753, p=0.198, HR 0.991, p=0.983 , for PIRCHE-I and –II respectively).
Conclusion: High numbers of PIRCHE-I lead to improved GVL effects after UCBT, while GVHD was not impacted by the number of PIRCHE. PIRCHE may provide an additional tool for individualized donor selection to improve survival chances. The effects observed in this study need to be validated in other cohorts.
Figure: Kaplan-Meier curve for the probability of relapse according to PIRCHE-I numbers. Patients presenting above median PIRCHE-I have a significantly reduced probability of relapse compared to those presenting lower numbers of PIRCHE-I.