Independent prognostic significance of minimal residual disease status in chronic lymphocytic leukaemia

Abstract Background Eradication of minimal residual disease (MRD) is an independent predictor of survival outcome in patients with chronic lymphocytic leukaemia (CLL) receiving fludarabine and cyclophosphamide (FC) or fludarabine, cyclophosphamide, and rituximab (FCR) as first-line treatment. Howeve...

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Published in:The Lancet (British edition) 2014-02, Vol.383, p.S66-S66
Main Authors: Kwok, Marwan, Dr, Rawstron, Andy, PhD, Varghese, Abraham, FRCPath, Evans, Paul, PhD, O'Connor, Sheila, PhD, Doughty, Chi, PhD, Newton, Darren, PhD, Moreton, Paul, FRCPath, Hillmen, Peter, Prof
Format: Article
Language:English
Subjects:
Bone marrow
Internal Medicine
Leukemia
Multivariate analysis
Survival
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Summary:Abstract Background Eradication of minimal residual disease (MRD) is an independent predictor of survival outcome in patients with chronic lymphocytic leukaemia (CLL) receiving fludarabine and cyclophosphamide (FC) or fludarabine, cyclophosphamide, and rituximab (FCR) as first-line treatment. However, the independent prognostic relevance of MRD status in other therapeutic settings is not clear. The goal of this study was to investigate the independent importance of achieving MRD negativity in CLL on progression-free survival (PFS) and overall survival (OS) with different treatments in frontline and relapsed or refractory settings compared with known prognostic markers. Methods We included all patients at our centre in Leeds and associated hospitals in West and North Yorkshire who had completed treatment for CLL from 1996 to 2007, achieved at least a partial response, and received an MRD assessment from a bone-marrow specimen after treatment. MRD assessments were done by multiparametric flow cytometry using CD5–CD19 in combination with CD20, CD22, CD32, CD38, CD79b, and CD81 in accordance with the international harmonised approach. 133 patients (17 receiving fludarabine, 65 fludarabine-based combination therapies, 26 alemtuzumab, and 25 other treatment including chlorambucil and autologous stem-cell transplantation) were followed up for a median of 5·2 years (IQR 3·0–7·3) to assess PFS and OS. Findings MRD negativity (defined as less than one CLL cell in 10 000 leucocytes) at the end of therapy independently correlated with both PFS (hazard ratio [HR] 3·22 [95% CI 2·09–4·97], Cox proportional hazards model p
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(14)60329-9