The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Author:

Ovechkina V.N.1,Bondarenko S.N.1ORCID,Morozova E.V.1,Moiseev I.S.1,Osipova A.A.1,Gindina T.L.1ORCID,Shakirova A.L.1,Bykova T.A.1,Kulagin A.D.1ORCID,Samorodova I.A.2,Karyakina E.V.3,Ukrainchenko E.A.4,Zubarovskaya L.S.1,Afanas'ev B.V.1

Affiliation:

1. R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

2. Municipal Clinical Hospital No. 31

3. Municipal Hospital No. 15

4. Aleksandrov Hospital

Abstract

Background & Aims. The aim of the study was to evaluate the efficacy and safety of azacytidine and decitabine prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia. Materials & Methods. The research included 62 patients who received hypomethylating agents (HMA) prior to allo-HSCT. The median age was 28 years (range from 1 to 68 years), the study population consisted of 27 (43.5 %) women and 35 (56.5 %) men. Results. The overall response (complete + partial remission) was observed in 42 % (n = 26) of cases. At the time of allo-HSCT no disease progression was observed in 41 (66 %) patients. The multivariant analysis showed the overall survival (OS) statistically significantly increased with the graft retention (hazard ratio [HR] 0.002; 95% confidence interval [95% CI] 0.001-0.74; p = 0.03), and also with the administration of HMA after allo-HSCT (HR 0.24; 95% CI 0.08-0.67; p = 0.007). The response (stabilisation, partial or complete remission) due to HMA administration prior to allo-HSCT (HR 6.4; 95% CI 0.75-54.0; p = 0.08) was associated with improved OS. The event-free survival (EFS) was significantly higher with the response to azacytidine and decitabine at the time of allo-HSCT (HR 38.9; 95% CI 1.3-1198.0; p = 0.03) and with the graft retention (HR 0.02; 95% CI 0.005-0.1; p = 0.001). In patients with MDS compared with AML (HR 2.3; 95% CI 0.9-22.0; p = 0.08), there was a tendency to EFS improvement. Progression-free survival rates were higher in patients with a number of blast cells in the bone marrow less than 31 % at the time of diagnosis (HR 1.1; 95% CI 1.1-9.9; p = 0.01). Conclusion. The use of azacytidine and decitabine prior to allo-HSCT allows to safely control the tumor mass in patients with MDS and to maintain the achieved remission with AML. In patients with a response to HMA, the best OS and EFS values are seen after allo-HSCT.

Publisher

Practical Medicine Publishing House

Subject

Oncology,Hematology

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