title: Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.
abstract: 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.
authors.affiliation: 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 ;
authors.forename: Liat
authors.initials: L
authors.lastname: Vidal
authors.affiliation: 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 ;
authors.forename: Ronit
authors.initials: R
authors.lastname: Gurion
authors.affiliation: a Davidoff Center, Rabin Medical Center , Institute of Hematology, Beilinson Hospital , Petah Tikva , Israel ;|c Bone Marrow Transplantation Unit , Sourasky Medical Center , Tel Aviv , Israel ;
authors.forename: Ron
authors.initials: R
authors.lastname: Ram
authors.affiliation: 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 ;
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
authors.affiliation: 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 ;
authors.forename: Osnat
authors.initials: O
authors.lastname: Bairey
authors.affiliation: d Department of Hematology , Medical University of Lodz and Copernicus Memorial Hospital , Lodz , Poland ;
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: a Davidoff Center, Rabin Medical Center , Institute of Hematology, Beilinson Hospital , Petah Tikva , Israel ;|e Department of Medicine , Beilinson Hospital, Rabin Medical Center , Petah Tikva , Israel ;
authors.forename: Anat
authors.initials: A
authors.lastname: Gafter-Gvili
authors.affiliation: a Davidoff Center, Rabin Medical Center , Institute of Hematology, Beilinson Hospital , Petah Tikva , Israel ;|f Department of Hematology , Assuta Medical Centers , Tel-Aviv , Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000209:etiology; D011379:Prognosis; D016016:Proportional Hazards Models; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil
keywords: CLL/SLL; Chemotherapy; chlorambucil; chronic lymphocytic leukemia; meta-analysis; small lymphocytic lymphoma; systematic review