Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who relapse after allogeneic hematopoietic cell transplantation (alloHCT) generally have poor overall survival (OS). Interventions that result in improved OS after relapse are not well established. The efficacy of second cellular therapy and specific indications are debated.
To study factors associated with post-relapse survival and efficacy of a second course of cellular therapy.
We retrospectively analyzed consecutive AML and MDS patients who received a first alloHCT between 2010 and 2017 at our center but subsequently relapsed. One-hundred-and-four patients with AML and 44 with MDS were included (total n=148). Bone marrow (BM) and peripheral blood stem cell (PBSC) grafts were either unmodified or T-cell depleted (TCD) by CD34+ selection ex-vivo. Forty-five patients (30.4%) received second cellular therapy after relapse, either a second alloHCT (n=28, 18.9%) or donor leukocyte infusion (n=17, 11.5%).
The median age at transplant was 60 years (range: 24-78). The median time to relapse (TTR) after transplant was 6.5 months (range: 1-60.9) and the ensuing median OS was 6 months (95% CI: 4.8-8.9). In univariable analysis, longer TTR, relapse type (MRD vs. morphologic), relapse occurring in the most recent years, and receipt of cellular therapy after relapse were associated with better outcomes, whereas adverse cytogenetics and/or abnormality of TP53, as well as NPM1 mutation in patients with AML, were associated with adverse outcomes. Relapse type, year of relapse, and a variable resulting from the combination of TTR and receipt of second cellular therapy remained significantly associated with post-relapse survival in multivariable analysis. In a separate multivariable model, only adjusted for TTR, relapse type, and receipt of second cellular therapy, an adverse effect of NPM1 mutation on survival was confirmed. We could not show an effect of post-transplant maintenance on survival after relapse. In both univariable and multivariable analysis, we found a positive association for second cellular therapy with survival after relapse in patients who relapsed early ( 12 months) after transplant. Two-year OS after second cellular therapy was 44.9% (95% CI: 28.5-61.4), and it was significantly better in patients with less than 5% BM blasts before cell infusion. We could not show a different effect on survival after second cellular therapy for DLI vs. second alloHCT in univariable analysis.
Survival after relapse is improving over time, but this remains a challenging event, especially for patients relapsing early after transplant. We showed that second cellular therapy could offer a benefit even in these cases. Still, more research is needed to clarify which are the most appropriate treatment choices after relapse. These are probably driven by underlying genetic and immunologic conditions, which should be the focus of future studies.

Copyright © 2021. Published by Elsevier Inc.