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Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents
Author(s) -
Alfonso Ana,
MontalbanBravo Guillermo,
Takahashi Koichi,
Jabbour Elias J.,
Kadia Tapan,
Ravandi Farhad,
Cortes Jorge,
Estrov Zeev,
Borthakur Gautam,
Pemmaraju Naveen,
Konopleva Marina,
BuesoRamos Carlos,
Pierce Sherry,
Kantarjian Hagop,
GarciaManero Guillermo
Publication year - 2017
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24735
Subject(s) - decitabine , medicine , chronic myelomonocytic leukemia , azacitidine , hypomethylating agent , natural history , international prognostic scoring system , gastroenterology , myelodysplastic syndromes , oncology , bone marrow , biochemistry , gene expression , chemistry , dna methylation , gene
Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML‐specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n = 151) treated with HMA. Mean age at diagnosis was 69 years (range 50‐88). According to the CMML‐specific prognostic scoring system (CPSS): 17 (15%) were low‐risk, 45 (39%) intermediate‐1 risk, 42 (36%) intermediate‐2, and 12 (10%) high‐risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow‐up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20‐28) and event‐free survival 14 months (95%CI: 11‐17). By multivariate analysis, age < 70 years, higher levels of hemoglobin, absence of blast in peripheral blood and lower CPSS cytogenetic risk predicted for better OS. CR was significantly higher in those patients treated with decitabine (58.3%) when compared with azacitidine (20.6%) ( P  < .001). 13 patients (9%) received allo‐SCT after a median of 4 cycles of HMA. 66 patients (50%) had HMA failure: 26 primary (34%) and 50 secondary (66%), including 35 (46%) that transformed to AML. Outcomes after HMA failure were poor with OS of 7 months (95%CI: 3‐12). In conclusion, HMA are effective in CMML but new agents and combinations are needed. This data could be a benchmark for further drug development in CMML.

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