Outcome After Azacitidine Treatment in Patients with High-Risk Myeolodysplastic Syndrome, Chronic Myelomonocytic Leukemia Type 2 and Acute Myeloid Leukemia – A Single Center Experience (Preliminary Data)

Abstract

Introduction: Hypomethylating agents have become a standard therapy for certain myeloid malignancies.Aim: The aim of this preliminary study was to assess efficacy and safety of azacitidine in patients with myelodysplas tic syndromes (MDS), chronic myelomonocytic leukemia with 10-29% blasts (CMML-2) and acute myeloid leukemia (AML) treated in a single center.Material and Methods: Twenty-six (69% male and 31% female, median age 67.8 years) patients (MDS, = 15; CMML-2, n = 2; AML, n = 9) treated with azacytidine in the period April 2017 to October 2018 year were included in the study. Disease assessment was performed after the 3rd cycle, 6th cycle, and at progression.Results: The median number of administered cycles was 6 (1-16). Erythroid response was achieved in 46.7% after 3rd cycle and 66.7% after 6th cycle. Platelet response was reached in 72.7% after 3rd cycle and 40% after 6th cycle and neutrophil hematological improvement in 27.3% and 50%, respectively. Only one patient (8.3%) progressed after the 6th cycle, stable disease or better marrow response was achieved in the others. The median progression free survival (PFS) and overall survival (OS) were 7.9 and 10.7 months in the MDS group and 9.7 and 11.5 months in the AML group, respectively. None of the patients with CMML-2 progressed at the end of the study. The only found factor to correlate with shortened PFS and OS was IPSS high risk MDS. The most frequent grade ≥ 3 adverse events was neutropenia 38.5%, followed by anemia 15.4% and thrombocytopenia 11.5%.Conclusion: The therapy with azacitidine is an option for elderly patients with high-risk MDS, AML and CMML-2 that provides PFS and OS for approximately one year irrespective of age or nosological subgroup. These are preliminary data and larger patient cohort and longer follow-up period are needed for clinical conclusions.

Azacitidine Treatment in Patients with Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia Type 2 and Acute Myeloid Leukemia According to their Cytogenetic Findings

“…The rates of thrombocytopenia (18.5%) and anemia (only 7%) were lower. These data are consistent with the fi ndings of other authors (Varbanova et al) who reported the most frequent adverse events being neutropenia 38.5%, followed by anemia 15.4% and thrombocytopenia 11.5% [6].…”

“…Yet in our patients, karyotype 46,XX,del(5q) or 46,XY,del(5q) was not detected. Nevertheless, Varbanova et al reported del(5q) in one patient with a good prognostic risk [6]. We report additional chromosome 8 and a partial deletion of chromosome 7 (deletion 7q) in two separate cases (Table 2).…”

“…It has become a standard therapy for high-risk myelodysplastic syndromes (MDS) and elderly patients with acute myeloid leukemia (AML) [4,5]. It is also an option for patients with CMML 2 that can provide patient free survival and overall survival for approximately one year irrespective of age or disease subgroup [6,7]. Azacitidine exhibits its antineoplastic activity via two mechanisms -by hypomethylation of DNA (inhibiting of DNA methyltransferase), and by direct cytotoxicity on abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA.…”