Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation

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.

Keywords: AML; MDS; allogeneic stem cell transplantation; azacitidine; relapse.

Figure 1

Overall survival (OS) after treatment with azacitidine ± DLI for relapse of myeloid neoplasms. OS of the study population comprising 151 patients was 38% (±9%) at 2 years.

Figure 2

Overall survival (OS) after treatment with azacitidine ± DLI in 151 patients based on a scoring system including relapse type and time between allo-HSCT and diagnosis of relapse. One point was assigned for molecular relapse, while two points were given for diagnosis of hematologic relapse. An interval between transplant and relapse of ≥6 months was assigned with zero points, while for relapse within the first 6 months after transplant one point was given. As such, the model enables a stratification of patients into three distinct risk categories (favorable = 1 point, intermediate = 2 points, unfavorable = 3 points).

Figure 3

Overall survival (OS) after treatment with azacitidine ± DLI in 66 patients with MDS and sAML with 20–29% BM blasts (formerly RAEB-T) based on a scoring system including relapse type and pretransplant strategy. One point was assigned for molecular relapse, while two points were given for diagnosis of hematologic relapse. Upfront transplantation was assigned zero points, while for application of HMA or intensive CTX prior transplant one point was given. As such, the model enables a stratification of patients into three distinct risk categories (favorable = 1 point, intermediate = 2 points, unfavorable = 3 points)