Treatment of Acute Myeloid Leukemias and Myelodisplastic Syndromes Relapsing After Allogeneic Stem Cell Transplantation: An In-Depth Analysis of the GITMO AML/MDS-Relapse Registry Study

Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) relapse is the most frequent cause of allogeneic stem cell transplantation (allo-SCT) failure. The utility of post-relapse therapy is controversial due to the high incidence of toxicity and the low efficacy. Methods: This sub-analysis of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) AML/MDS relapse study focuses on 647 AML/MDS relapsing after allo-SCT performed between 2015 and 2021. Following the relapse, these patients were treated with either hypomethylating agents (HMAs)-based therapy (n = 308) or other treatments (n = 339), including intensive chemotherapy, FLT3-inhibitors, and second allo-SCT. Results: HMAs-based therapies were more frequently used in older patients, transplanted not in CR following a reduced-intensity conditioning regimen. The overall response rate (ORR) with or without HMA-based salvage treatment was 33% and 40%, respectively (P = .006). The complete remission (CR) rate was 23% and 33% in the two groups, respectively (P < .001). The long-term OS and TRM of the two groups were superimposable. Independently from the type of salvage, an advantage in OS was observed when donor lymphocytes infusion (DLI) was included (P < .001). Relapse within 12 months after SCT, low disease burden at relapse, and the CR status at transplant confirmed their independent strong prognostic impact on both HMA and non-HMA-based group (HR 0.05, 0.44, and 0.49 and HR 0.19, 0.32, and 0.53, respectively). Conclusions: Despite the lower ORR observed with HMA-based therapy, the long-term OS was comparable to that observed with other therapies. The immune control of the disease relapse with DLI is of benefit, independently from the salvage therapy. .