Definition of disease-progression risk stratification in untreated chronic lymphocytic leukemia using combined clinical, molecular and virological variables

Abstract

Prognoses of persons with chronic lymphocytic leukemia (CLL) including time-to-therapy (TTT) and survival is heterogeneous. Risk factors and predictive scoring systems are mostly developed in persons of predominately European descent with CLL. Whether these systems accurately predict TTT and survival of Han Chinese with CLL is unknown. We interrogated clinical and laboratory data from 334 newly diagnosed, untreated Chinese CLL without treatment indication upon diagnosis to identify variables associated with TTT and develop a prognostic score. Binet stage, blood lymphocyte level, TP53 abnormality, unmutated IGHV, prior HBV, and EBV infections were independently associated with TTT in multivariate analyses. We constructed a prognostic score dividing subjects into cohorts with low, intermediate, and high risk from diagnosis to TTT. Median TTTs were 139 months (range, 85-189 months), 25 months (12-38 months), and 4 months (1-7 months; P-value for trend <0.001). We identified variables associated with TTT in Chinese with CLL with no treatment indication and developed a predictive model for survival. Some variables associated with TTT are similar to those of persons of predominately European descent, whereas others, such as HBV and/or EBV infections, operate in Chinese and Europeans but are not currently included in prognostic and predictive staging systems in persons of European descent. They should be investigated.

Keywords: CLL; Epstein Barr virus; hepatitis B virus; prognoses.