Haploidentical versus Double-Cord Blood Stem Cells as a Second Transplantation for Relapsed Acute Myeloid Leukemia

SIMPLE SUMMARY: Second stem cell transplantation (SCT2) may provide long-term remission for patients with relapsed acute myeloid leukemia (AML) after the first transplantation (SCT1). There are increasing demands for alternative donors, namely haploidential and umbilical cord blood, even in SCT2. In this single-center retrospective analysis for AML patients who relapsed after SCT1, we compared SCT2 outcomes with haploidentical donors (HIT) or double-cord blood (dCBT). In our study, HIT had superior transplant outcomes to dCBT as SCT2 in AML, due to the high non-relapse mortality in the dCBT group, which resulted in poorer survival. In a subgroup analysis, pre-transplant WT1-MRD positivity was associated with higher relapse rates and worse outcomes. ABSTRACT: There are limited data on second stem cell transplantation (SCT2) outcomes with alternative donors for relapsed AML after the first stem cell transplantation (SCT1). We analyzed the outcomes of 52 adult AML patients who received SCT2 from haploidentical donors (HIT, N = 32) and double-cord blood (dCBT, N = 20) between 2008 and 2021. The HIT group received T-cell-replete peripheral blood stem cells after reduced-toxicity conditioning with anti-thymocyte globulin (ATG), while the dCBT group received myeloablative conditioning. For a median follow-up of 64.9 months, the HIT group, compared to the dCBT group, had earlier engraftment, superior 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) with similar relapse. Multivariate analysis demonstrated that HIT was significantly associated with better OS, DFS, and lower NRM than dCBT. Both longer remission duration after SCT1 and complete remission at SCT2 were significantly associated with a lower relapse rate. In addition, bone marrow WT1 measurable residual disease (MRD) positivity was significantly associated with inferior OS and higher relapse. This study suggests that T-cell-replete HIT with ATG-based GVHD prophylaxis may be preferred over dCBT as SCT2 for relapsed AML and that WT1-MRD negativity may be warranted for better SCT2 outcomes.