title: Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents.
abstract: 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.
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Ana
authors.identifier: http://orcid.org/0000-0002-2478-5354
authors.initials: A
authors.lastname: Alfonso
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Montalban-Bravo
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Elias J
authors.identifier: http://orcid.org/0000-0003-4465-6119
authors.initials: EJ
authors.lastname: Jabbour
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Naveen
authors.identifier: http://orcid.org/0000-0002-1670-6513
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: Departments of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Hagop
authors.identifier: http://orcid.org/0000-0002-1908-3307
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Departments of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, 77015, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers