title: A network meta-analysis of progression free survival and overall survival in first-line treatment of chronic lymphocytic leukemia.
abstract: BACKGROUND
  A limited evidence exists regarding comparisons of clinical effectiveness of available therapies for first-line treatment of chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  We compared available therapies for treatment-naïve, symptomatic CLL regarding progression free survival (PFS) and overall survival (OS) in all the identified random control trials and in subgroups composed of younger/fit and older/unfit patients, using a Bayesian network meta-analysis.
  
  
  RESULTS
  In younger/fit patients we obtained median of projected mean PFS of: 19, 26, 31, 43, 51 and 75months for chlorambucil, fludarabine, alemtuzumab, fludarabine with cyclophosphamide (FC), bendamustine and fludarabine with cyclophosphamide and rituximab (FCR), respectively. We noted median OS of: 59, 66, 66, 70months for FC, chlorambucil, FCR and fludarabine, respectively. In older/unfit patients we noted PFS of: 16, 17, 24, 30, 60months for chlorambucil, fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and 90months for fludarabine, RClb, chlorambucil and GClb, respectively.
  
  
  CONCLUSIONS
  Our results suggest that: (1) FCR has higher potential of preventing CLL progression in younger/fit patients over four therapy options, which were subject of previous meta-analysis but also over bendamustine; (2) in these patients FCR does not entail prolonging of OS in comparison with chlorambucil and it is outperformed by fludarabine; (3) in older/unfit patients GClb demonstrates longer projected PFS than all assessed comparators; (4) in this group GClb has also the highest potential of increasing OS.
authors.affiliation: Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 4 Trojdena Street, 02-109 Warsaw, Poland. Electronic address: pladyzynski@ibib.waw.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ladyzynski
authors.affiliation: Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 4 Trojdena Street, 02-109 Warsaw, Poland. Electronic address: mmolik@ibib.waw.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Molik
authors.affiliation: Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 4 Trojdena Street, 02-109 Warsaw, Poland. Electronic address: pfoltynski@ibib.waw.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Foltynski
mesh_terms: D000367:Age Factors; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001499:Bayes Theorem; D000069461:Bendamustine Hydrochloride; D002699:Chlorambucil / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality*; D008390:Markov Chains; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D015649:Pentostatin / Q000008:administration & dosage; D010809:Physical Fitness; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D002699:Chlorambucil; D015649:Pentostatin; D000074323:Alemtuzumab; D000069283:Rituximab; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C527517:ofatumumab; C543332:obinutuzumab; C024352:fludarabine
keywords: B-cell; CLL; Chronic; Leukemia; Lymphocytic; Meta-analysis