Efficiency of 5-azacytidine administration before allogeneic hematopoietic stem cell transplantation in acute myelobastic leukemia, myelodysplastic syndrome, and juvenile myelomonocytic leukemia
Contact: Dr. Varvara N.Ovechkina,
E-mail: ovetchkina@gmail.com
Accepted 29 September 2016
Summary
Introduction
The aim of our study was to assess overall survival (OS), time to progression and event-free survival (EFS) in patients with acute myelobastic leukemia (AML), myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML) who underwent therapy with hypomethylating agents (HMA) before before allogeneic hematopoietic stem cell transplantation (HSCT).
Patients and Methods
We have performed analysis of 54 cases including 15 AML (28%), 33 MDS ( 61%), 4 JMML (7%), 2 CMML(4%), at a mean age of 33 years old (3 mo to 61 years old). Male-to-female ratio was 54:46. Cytogenetic risk group at diagnosis was estimated as favorable in 22 cases (41%); intermediate, in 13 patients (24%), and unfavorable, in 18 cases (35%). In course of preparation for HSCT, 60% of the patients were treated with 5-azacytidine (5-Aza), 35% were administered Decytabine (Dec), and 5% of the patients were treated with the both drugs. The mean number of treatment rounds was (1 to 12). All the patients then underwent allo-HSCT including 11 transplants (20% of total) from a related HLA compatible donor; 30 patients (55%) were transplanted from matched unrelated donors. In 5 patients (10%), hematopoietic grafts were taken from unrelated HLA-compatible donors, and 8 transplants (15%) were performed from haploidentical donors.
Results
Eight patients exhibited progression despite the therapy performed; in 30 cases (56%), we have observed stabilization (S) of the disease, fourteen patients (26%) achieved partial remission (PR), and complete remission (CR) was observed in two cases (4%). CR or PR were registered after an average of 3 rounds of the therapy (1 to 5 courses). Progression of disease by the time of HSCT was documented in 10 patients (18%). The median OS value in the group was 778 days (95%CI, 346-1025 days). The OS terms differed significantly between the patients with AML (382 days; 95% CI, 134-1029) and MDS (1036 days; 95% CI, 619-1452, р=0.05). The median of time-to-progression comprised 593 days (95% CI, 169-1016). Posttransplant relapse developed in 19 cases (35% of total group). At the present time, 23 patients (43% of total) are alive. The main causes of death were as follows: relapse/progression of primary disease (13.4%), infection (10.3%), hemorrhagic complications (4.1%), graft-versushost disease (3.1%), and second malignancy (1.3%). The EFS median was 661 day (95% CI, 1-1346). Median EFS values were significantly higher for the patients who achieved stabilization or remission state (956 days; 95% CI, 689-1224) and for those who retained this state by the time of allo-HSCT (1062 days; 95% CI, 790-1333) as compared with patients who did not respond to hypomethylating therapy (300 days; 95% CI, 108-491) and had developed progression at the time of allo-HSCT (306 days; 95% CI, 171-442, p=0.02).
Conclusion
Hypomethylating agents may be drugs of choice for the patients with AML, MDS, CMML, and JMML during preparation for allo-HSCT. Taking into account the time-to-progression values in this cohort of patients, the start of HMA therapy should coincide with decision on unrelated donor search. Post-transplant EFS results proved to be better in HMA responders. To obtain more reliable results, further studies are required with larger numbers of patients
Keywords
Myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, acute myeloid leukemia, hypomethylating therapy
Accepted 29 September 2016