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Impact of telomere length on the outcome of allogeneic stem cell transplantation for poor‐risk chronic lymphocytic leukaemia: results from the GCLLSG CLL3X trial

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Chronic lymphocytic leukaemia (CLL) is the most common malignancy of the B cell system, affecting predominantly the elderly, with a median diagnostic age around 72 years (Rai, 2015). CLL has… Click to show full abstract

Chronic lymphocytic leukaemia (CLL) is the most common malignancy of the B cell system, affecting predominantly the elderly, with a median diagnostic age around 72 years (Rai, 2015). CLL has a very heterogeneous clinical course ranging from indolent disease to genetically-defined poor prognostic groups with aggressive course under standard chemoimmunotherapy (Zenz et al, 2010; Stilgenbauer et al, 2015). Although novel signalling pathway inhibitors have changed the therapeutic landscape (Rai, 2015; Stilgenbauer et al, 2015), allogeneic stem cell transplantation (allo-SCT) has been shown to be the only curative therapy in patients with high-risk CLL, overcoming the impact of adverse prognostic factors. The German CLL study group (GCLLSG) CLL3X study evaluated allo-SCT in patients with poor risk CLL. Overall survival (OS) was 53% after a median follow-up of 6 years (0 6–10 8 years), (Dreger et al, 2010). The primary factors associated with outcome were prior response to chemotherapy and minimal residual disease clearance after allo-SCT, but not genetic markers (including high-risk characteristics, e.g., 17p-, mutated TP53) (Dreger et al, 2013, 2010). Among the many prognostic factors, short telomere length was shown to be an independent adverse factor in CLL (Roos et al, 2008; Rampazzo et al, 2012; Mansouri et al, 2013; Lin et al, 2014). Short telomeres at diagnosis are associated with poor-risk clinical and biological disease characteristics (Roos et al, 2008; Mansouri et al, 2013; Lin et al, 2014), but the impact of telomere length following allo-SCT has never been studied. We analysed telomere length on samples from CLL3X (N = 58), at baseline prior to allo-SCT and studied associations with disease characteristics and impact on survival. The CLL3X trial was a multicentre phase 2 clinical study, described previously (Dreger et al, 2013, 2010), which included 100 patients (median age, 53 years; range: 27–65 years). A representative cohort of 58 patients was included for analysis of telomere length (Table S1). As the samples were not CD19 enriched, only cases fulfilling at least one of the criteria in Table S2 were included to ensure analysis of CLL tumour cell telomere length. The study was approved by the institutional review boards

Keywords: poor risk; cll; risk; allo sct; telomere length; cell

Journal Title: British Journal of Haematology
Year Published: 2017

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