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Keywords: chronic lymphocytic leukaemia; chemotherapy; clinical trial; monoclonal antibody; minimal residual disease EN chronic lymphocytic leukaemia chemotherapy clinical trial monoclonal antibody minimal residual disease 646 650 5 07/29/21 20210801 NES 210801 Chemoimmunotherapy (CIT) comprising cytotoxics and anti-CD20 monoclonal antibodies (mab) has long been the therapeutic mainstay for chronic lymphocytic leukaemias (CLL). COSMIC, c hemotherapy plus o fatumumab at s tandard or m ega-dose i n c hronic lymphocytic leukaemia, a phase II randomised study. [Extracted from the article]

A letter to the editor is presented related to the impact of pathogenesis in chronic lymphocytic leukaemia and Hodgkin lymphoma on multiple myeloma.

The article reports that genetic alterations in the ataxia telangiectasia‐mutated (ATM)‐TP53 DNA damage response (DDR) pathway represent an important mechanism of chemoresistance to conventional chemotherapeutic agents and also drive genomic instability. It mentions that ATM protein plays a critical role in the DNA damage response to double strand breaks. It presents use of olaparib in patients with relapsed chronic lymphocytic leukaemia, T‐prolymphocytic leukaemia or mantle cell lymphoma.

Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis ( STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia ( CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival ( P < 0·0001; Hazard ratio [ HR] = 13·2, 95% confidence interval [ CI] = 11·6-106·4) and this was preserved in early-stage disease patients ( P < 0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL. [ABSTRACT FROM AUTHOR]

Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high‐resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere ‘fusogenic’ range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P < 0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI] = 11·6–106·4) and this was preserved in early‐stage disease patients (P < 0·0001, HR=19·3, 95% CI = 17·8–802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high‐resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL. [ABSTRACT FROM AUTHOR]