Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia

作者：Chiara Elena, Anna Gallì, Esperanza Such, Manja Meggendorfer, Ulrich Germing, Ettore Rizzo, José Cervera, Elisabetta Molteni, Annette Fasan, Esther Schuler, Ilaria Ambaglio, Maria López‐Pavía, Silvia Zibellini, Andrea Kuendgen, Erica Travaglino, Reyes Sancho-Tello, Silvia Catricalà, Ana I. Vicente, Torsten Haferlach, Claudia Haferlach, Guillermo Francisco Sanz, Luca Malcovati, Mario Cazzola · 发表于：Blood · 年份：2016 · DOI：10.1182/blood-2016-05-714030 · 被引用次数：367 · 研究领域：Acute Myeloid Leukemia Research、Chronic Myeloid Leukemia Treatments、Myeloproliferative Neoplasms: Diagnosis and Treatment

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm with variable clinical course. To predict the clinical outcome, we previously developed a CMML-specific prognostic scoring system (CPSS) based on clinical parameters and cytogenetics. In this work, we tested the hypothesis that accounting for gene mutations would further improve risk stratification of CMML patients. We therefore sequenced 38 genes to explore the role of somatic mutations in disease phenotype and clinical outcome. Overall, 199 of 214 (93%) CMML patients carried at least 1 somatic mutation. Stepwise linear regression models showed that these mutations accounted for 15% to 24% of variability of clinical phenotype. Based on multivariable Cox regression analyses, cytogenetic abnormalities and mutations in RUNX1, NRAS, SETBP1, and ASXL1 were independently associated with overall survival (OS). Using these parameters, we defined a genetic score that identified 4 categories with significantly different OS and cumulative incidence of leukemic evolution. In multivariable analyses, genetic score, red blood cell transfusion dependency, white blood cell count, and marrow blasts retained independent prognostic value. These parameters were included into a clinical/molecular CPSS (CPSS-Mol) model that identified 4 risk groups with markedly different median OS (from >144 to 18 months, hazard ratio [HR] = 2.69) and cumulative incidence of leukemic evolution (from 0% to 48% at 4 years, HR = ...