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.
An improved understanding of relapse kinetics is required to optimize detection and treatment strategies for the post-transplant relapse of myeloid neoplasms. Therefore, we retrospectively analyzed data from 91 patients allografted for MDS (n = 54), AML-MRC (n = 29) and chronic myelomonocytic leukemia (CMML, n = 8), who relapsed after transplant. Patients with early (<12 months, n = 56) and late relapse (>12 months, n = 35) were compared regarding patient-, disease- and transplant-related factors, including karyotype analyses at diagnosis and relapse. After a median follow-up of 17.4 months after relapse, late relapses showed improved outcomes compared with early relapses (2-yr OS 67% vs. 32%, p = 0.0048). Comparing frequency of distinct patient-, disease- and transplant-related factors among early and late relapses, complex karyotype (p = 0.0004) and unfavorable disease risk at diagnosis (p = 0.0008) as well as clonal evolution at relapse (p = 0.03) were more common in early than in late relapses. Furthermore, patients receiving transplant without prior cytoreduction or in complete remission were more frequently present in the group of late relapses. These data suggest that cytogenetics rather than disease burden at diagnosis and transplant-related factors determine the timepoint of post-transplant relapse and that upfront transplantation may be favored in order to delay relapse.
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