Do we need to analyse everything at diagnosis in chronic lymphocytic leukaemia?

Abstract

Keywords: chronic lymphocytic leukaemia, heterogeneous disease, prognostic factors.Chronic lymphocytic leukaemia (CLL) is an extremely heterogeneous disease in terms of its clinical course and a variety of biomarkers have been described that have powerful prognostic and predictive outcome. An important question is how can this be added to by the more recent identification of recurrent genetic mutations in CLL. In the current paper, (Hu et al., 2019) the authors studied the impact on time from diagnosis to time to first treatment (TTFT) of detection of mutations in a 29 gene panel and looked for associations with a variety of standard prognostic factors in a cohort of 384 treatment na€ ıve CLL. They demonstrate that mutated ATM (P < 0Á001), NOTCH1 (P < 0Á001) and SF3B1 (P = 0Á002) as well as unmutated IGHV (P < 0Á001), del(11q) (P < 0Á001) and trisomy 12 (P < 0Á001) by hierarchal FISH and advanced Rai (P = 0Á05) and Binet (P < 0Á001) stages were associated with shorter TTFT. In a multivariable analysis, mutated ATM (P < 0Á001) and unmutated IGHV status (P < 0Á001) remained significant, and the authors suggest that these factors are therefore important in early leukemogenesis. Surprisingly, in this cohort and in contrast to previous studies, the very high-risk prognostic factors del(17p), mutated TP53 and complex karyotype were not associated with shorter TTFT and the authors suggest further that these factors may have less impact in early disease progression, but are more important in terms of response to chemotherapy and at later times in the clinical course of CLL.Up to 80% of CLL patients are now diagnosed incidentally and are asymptomatic at diagnosis. Many patients remain asymptomatic over decades and 20-30% have a life expectancy not significantly different from the general population (Rossi et al., 2013), while others progress rapidly to requirement for treatment with extensive lymphadenopathy, hepatosplenomegaly, and cytopoenias.