Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: A Mayo Clinic-French Consortium Study

Emnet A. Wassie, Raphael Itzykson, Terra L. Lasho, Olivier Kosmider, Christy M. Finke, Curtis A. Hanson, Rhett P. Ketterling, Eric Solary, Ayalew Tefferi, Mrinal M. Patnaik

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)1111-1115
Number of pages5
JournalAmerican journal of hematology
Volume89
Issue number12
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Hematology

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