title: Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes.
abstract: We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. In univariate analysis, significant risk factors for survival included anemia, thrombocytopenia, increased levels of white blood cells, absolute neutrophils, absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone marrow blasts, and presence of circulating immature myeloid cells (IMCs). Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. On multivariable analysis, increased AMC (>10 × 10(9)/l, relative risk (RR) 2.5, 95% confidence interval (CI) 1.7-3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4-2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2-2.2) and decreased platelet count (<100 × 10(9)/l, RR 1.4, 99% CI 1.0-1.9) remained significant. Using these four risk factors, a new prognostic model for overall (high risk, RR 4.4, 95% CI 2.9-6.7; intermediate risk, RR 2.0, 95% CI 1.4-2.9) and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9-12.8; intermediate risk, RR 2.6, 95% CI 1.1-5.9) performed better than other conventional risk models and was validated in an independent cohort of 268 CMML patients.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Patnaik
authors.forename: E
authors.initials: E
authors.lastname: Padron
authors.forename: R R
authors.initials: RR
authors.lastname: LaBorde
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.forename: C M
authors.initials: CM
authors.lastname: Finke
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.forename: J M
authors.initials: JM
authors.lastname: Hodnefield
authors.forename: R A
authors.initials: RA
authors.lastname: Knudson
authors.forename: R P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: A
authors.initials: A
authors.lastname: Al-kali
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: N A
authors.initials: NA
authors.lastname: Ali
authors.forename: R S
authors.initials: RS
authors.lastname: Komrokji
authors.forename: R S
authors.initials: RS
authors.lastname: Komroji
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics* / Q000401:mortality*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D000072260:RNA Splicing Factors; D012097:Repressor Proteins / Q000235:genetics*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D012307:Risk Factors; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000235:genetics*; D000072668:Splicing Factor U2AF; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000401:mortality; D014944:World Health Organization; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D012261:Ribonucleoproteins; C112491:SF3B1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors