Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a M ayo C linic‐ F rench C onsortium S tudy

Four hundred and nine patients with chronic myelomonocytic leukemia (CMML) were included in the international collaborative study (268 (66%) and 141 (34%) from Mayo clinic and French consortium respectively). Thirty percent displayed an abnormal karyotype, including; 72% sole, 16% two, and 11% complex abnormalities. The most common abnormalities included; +8 (23%), ‐Y (20%), ‐7/7q‐(14%), 20q‐ (8%), +21 (8%), and der(3q) (8%). Patients with an abnormal karyotype were more likely to be elderly ( P  = 0.03), be anemic ( P  = 0.0009), have leukocytosis ( P  = 0.02) with neutrophilia ( P  = 0.03), demonstrate increased circulating immature myeloid cells ( P  = 0.0003), peripheral blood blasts ( P  < 0.0001), and bone marrow blasts ( P  < 0.0001). ASXL1 ( P  = 0.04) and SF3B1 ( P  = 0.03) mutations clustered with an abnormal karyotype, whereas SRSF2 ( P  = 0.02) mutations occurred more commonly with a normal karyotype. A step‐wise survival analysis resulted in three distinct cytogenetic risk categories: high (complex and monosomal karyotypes), intermediate (all abnormalities not in the high or low risk groups) and low [normal, sole ‐Y and sole der (3q)] with median survivals of 3 [hazard ratio (HR) = 8.1, 95% confidence interval (CI) = 4.6–14.2], 20 (HR = 1.7, 95% CI = 1.2–2.3) and 41 months, respectively. In multivariable analysis, this particular cytogenetic risk stratification remained significant in the context of the Molecular Mayo Model ( P  < 0.0001), MD Anderson prognostic model ( P  < 0.0001), the GFM CMML model ( P  < 0.0001) and was effective in predicting leukemic transformation ( P  = 0.004). Am. J. Hematol. 89:1111–1115, 2014. © 2014 Wiley Periodicals, Inc.