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

Abstract：

: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 = 3.84) (P < .001). The CPSS-Mol fully retained its ability to risk stratify in an independent validation cohort of 260 CMML patients. In conclusion, integrating conventional parameters and gene mutations significantly improves risk stratification of CMML patients, providing a robust basis for clinical decision-making and a reliable tool for clinical trials.

journal_name

Blood

journal_title

Blood

authors

Elena C,Gallì A,Such E,Meggendorfer M,Germing U,Rizzo E,Cervera J,Molteni E,Fasan A,Schuler E,Ambaglio I,Lopez-Pavia M,Zibellini S,Kuendgen A,Travaglino E,Sancho-Tello R,Catricalà S,Vicente AI,Haferlach T,Haferlach

doi

10.1182/blood-2016-05-714030

subject

Has Abstract

pub_date

2016-09-08 00:00:00

pages

1408-17

issue

eissn

0006-4971

issn

1528-0020

pii

blood-2016-05-714030

journal_volume

128

pub_type

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