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Leuk Lymphoma. 2016 Sep;57(9):2047-57. doi: 10.3109/10428194.2016.1154956. Epub 2016 Mar 16.

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

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a Davidoff Center, Rabin Medical Center , Institute of Hematology, Beilinson Hospital , Petah Tikva , Israel ;
b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel ;
c Bone Marrow Transplantation Unit , Sourasky Medical Center , Tel Aviv , Israel ;
d Department of Hematology , Medical University of Lodz and Copernicus Memorial Hospital , Lodz , Poland ;
e Department of Medicine , Beilinson Hospital, Rabin Medical Center , Petah Tikva , Israel ;
f Department of Hematology , Assuta Medical Centers , Tel-Aviv , Israel.


Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.


CLL/SLL; Chemotherapy; chlorambucil; chronic lymphocytic leukemia; meta-analysis; small lymphocytic lymphoma; systematic review

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