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Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a M ayo C linic‐ F rench C onsortium S tudy
Author(s) -
Wassie Emnet A.,
Itzykson Raphael,
Lasho Terra L.,
Kosmider Olivier,
Finke Christy M.,
Hanson Curtis A.,
Ketterling Rhett P.,
Solary Eric,
Tefferi Ayalew,
Patnaik Mrinal M.
Publication year - 2014
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.23846
Subject(s) - medicine , chronic myelomonocytic leukemia , leukocytosis , gastroenterology , hazard ratio , neutrophilia , context (archaeology) , myeloid leukemia , leukemia , karyotype , bone marrow , pathology , myelodysplastic syndromes , immunology , biology , confidence interval , genetics , gene , paleontology , chromosome
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.