Defining the prognosis of early stage chronic lymphocytic leukaemia patients

Chris Pepper, Aneela Majid, Thet Thet Lin, Saman Hewamana, Guy Pratt, Renata Walewska, Stefan Gesk, Reiner Siebert, Simon Wagner, Ben Kennedy, Fiona Miall, Zadie A Davies, Ian Tracy, Anne C Gardiner, Paul Brennan, Robert Hills, Martin J.S Dyer, David Oscier, Chris Fegan

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


Approximately 70% of chronic lymphocytic leukaemia (CLL) patients present with early stage disease, therefore defining which patients will progress and require treatment is a major clinical challenge. Here, we present the largest study of prognostic markers ever carried out in Binet stage A patients (n = 1154) with a median follow‐up of 8 years. We assessed the prognostic impact of lymphocyte doubling time (LDT), immunoglobulin gene (IGHV) mutation status, CD38 expression, ZAP‐70 expression and fluorescence in situ hybridization (FISH) cytogenetics with regards to time to first treatment (TTFT) and overall survival (OS). Univariate analysis revealed LDT as the most prognostic parameter for TTFT, with IGHV mutation status most prognostic for OS. CD38 expression, ZAP‐70 expression and FISH were also prognostic variables; combinations of these markers increased prognostic power in concordant cases. Multivariate analysis revealed that only LDT, IGHV mutation status, CD38 and age at diagnosis were independent prognostic variables for TTFT and OS. Therefore, IGHV mutation status and CD38 expression have independent prognostic value in early stage CLL and should be performed as part of the routine diagnostic workup. ZAP‐70 expression and FISH were not independent prognostic markers in early stage disease and can be omitted at diagnosis but FISH analysis should be undertaken at disease progression to direct treatment strategy.
Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalBritish Journal of Haematology
Issue number4
Early online date15 Dec 2011
Publication statusPublished - Feb 2012
Externally publishedYes


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