Abstract
To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after a median of 4 cycles and lasted for a median of 11 months (range 0.9 to 120 months). With a median follow-up of 22 months (range: 1 to 122 months), the 2-year survival rate was 38% ± 9%, including 17 patients with ongoing remission for >5 years. Based on results from multivariate analyses, molecular relapse and time to relapse were integrated into a score, clearly dividing patients into 3 subgroups with CR rates of 71%, 39%, and 29%; and 2-year survival rates of 64%, 38%, and 27%, respectively. In the subgroup of MDS and secondary AML, receiving upfront transplantation was associated with superior response and survival, and therefore pretransplant strategy was integrated together with relapse type into a MDS–sAML-specific score. Overall, Aza enables meaningful responses and long-term survival, which is a predictable with a simple-to-use scoring system.
Highlights
During the last decade, the hypomethylating agents (HMA) azacitidine (Aza) and decitabine (DAC) have become a clinically relevant treatment option for patients with relapse of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation [1,2,3,4,5]
This retrospective analysis includes 151 patients with AML, MDS, and MPN, who were treated with Aza and envisaged donor lymphocyte infusions (DLI) as first salvage therapy for relapse after allo-HSCT at our center between 2005 and 2019
Molecular relapse was defined as a decrease of donor chimerism to
Summary
The hypomethylating agents (HMA) azacitidine (Aza) and decitabine (DAC) have become a clinically relevant treatment option for patients with relapse of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1,2,3,4,5] This was based on several retrospective analyses, as well as a few prospective single-arm trials reporting response rates ranging from 10% to 35% and 2-year overall. Two of these analyses identified diagnosis of MDS instead of AML and disease burden at relapse as predictors for response and survival [7,11], while results regarding the interval between transplant and relapse were controversial This controversy and limited knowledge about predictive factors probably results in part from limited data access in these registry-based analyses, as well as different inclusion criteria, with one analysis including molecular relapses and one only focusing on hematologic relapses.
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