Second Transplantation for Relapsed Hematologic Malignancies After First Allogeneic Hematopoietic Stem Cell...

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HCT) from human leukocyte antigen (HLA)-matched related donors (MRDs) remains a major clinical challenge. While second allo-HCT may be curative, the optimal donor selection strategy for such patients remains unclear.

This study aimed to evaluate the impact of donor change in patients who relapse following allo-HCT from an MRD, and to clarify its effect on outcomes after second allo-HCT.

Using data from the Japanese national transplant registry, we retrospectively analyzed 922 individuals who relapsed after first allo-HCT from an MRD and underwent a second allo-HCT between 2001 and 2021. Donor sources comprised the same MRD (SM-RD), a different MRD, HLA-mismatched related donors (1MM-RD, 23MM-RD), matched or mismatched unrelated donors (M-UD, 1MM-UD), and unrelated cord blood (U-CB).

In multivariate analysis, transplantation from 23MM-RDs was significantly associated with inferior overall survival (OS) compared with SM-RDs (HR, 1.49; P = 0.0062), while other donor sources were not. Additional adverse prognostic factors included non-remission at second transplant, poor performance status, and early relapse (<6 months after first transplant). Same donor selection did not correlate with increased non-relapse mortality, and donor change did not confer a survival advantage, suggesting that SM-RD remains a valid and reasonable option. In an additional sensitivity analysis, the association between 23MM-RD and inferior OS was attenuated and was not statistically significant in the contemporary era (2015-2021), although the donor-by-era interaction was not significant.

These findings emphasize the clinical relevance of donor selection after relapse following allo-HCT from an MRD and highlight the need for prospective studies to refine donor selection strategies in this setting.