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

BONE MARROW TRANSPLANTATION , , , ,

VN Ovechkina1, SN Bondarenko1, EV Morozova1, IS Moiseev1, AA Osipova1, TL Gindina1, AI Shakirova1, TA Bykova1, AD Kulagin1, IA Samorodova2, EV Karyakina3, EA Ukrainchenko4, LS Zubarovskaya1, BV Afanas’ev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

3 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

4 Aleksandrov Hospital, 4 Solidarnosti pr-t, Saint Petersburg, Russian Federation, 193312

For correspondence: Varvara Nikolaevna Ovechkina, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-72; e-mail ovetchkina@gmail.com

For citation: Ovechkina VN, Bondarenko SN, Morozova EV, et al. The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Clinical oncohematology. 2017;10(3):351–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-351-357

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.

Keywords: acute myeloid leukemia, myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, hypomethylating agents, azacitidine, decitabine.

Received: December 19, 2016

Accepted: March 9, 2017

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