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

References

• Zent CS, Kyasa MJ, Evans R, et al. Chronic lymphocytic leukemia incidence is substantially higher than estimated from tumor registry data. Cancer. 2001;92:1325–1330.
   PubMed Web of Science ®Google Scholar
• Seftel MD, Demers AA, Banerji V, et al. High incidence of chronic lymphocytic leukemia (CLL) diagnosed by immunophenotyping: a population-based Canadian cohort. Leuk Res. 2009;33:1463–1468.
   PubMed Web of Science ®Google Scholar
• Howlader N, Noone A, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2012. Bethesda (MD): National Cancer Institute.
   Google Scholar
• Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219–234.
   PubMed Web of Science ®Google Scholar
• Tsimberidou AM, Wen S, O’Brien S, et al. Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2007;25:4648–4656.
   PubMed Web of Science ®Google Scholar
• Swerdlow S, Campo E, Harris, NL, et al. World health organization classification of tumours of haematopoietic and lymphoid tissues. France: IARC Press; 2008.
   Google Scholar
• Gribben JG. How I treat CLL up front. Blood. 2009;115:187–197.
   PubMed Web of Science ®Google Scholar
• Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol2007;25:5616–5623.
   Google Scholar
• Jaksic B, Brugiatelli M, Krc I, et al. High dose chlorambucil versus Binet’s modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. Int Cancer. 1997;79:2107–2114.
   Google Scholar
• Robak T, Bloński JZ, Kasznicki M, et al. Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial. Blood. 2000;96:2723–2729.
   PubMed Web of Science ®Google Scholar
• Richards S, Clarke M, Wheatley K, et al. Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials. J Natl Cancer Inst. 1999;91:861–868.
   PubMedGoogle Scholar
• Steurer M, Pall G, Richards S, et al. Cochrane database of systematic reviews. Chichester: John Wiley & Sons, Ltd; 1996. p. CD004270.
   Google Scholar
• Eichhorst BF, Busch R, Stilgenbauer S, et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009;114:3382–3391.
   PubMed Web of Science ®Google Scholar
• Knauf WU, Lissichkov T, Aldaoud A, et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009;27:4378–4384.
   PubMed Web of Science ®Google Scholar
• Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370:1101–1110.
   PubMed Web of Science ®Google Scholar
• Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373:2425–2437.
   PubMed Web of Science ®Google Scholar
• Hillmen P, Robak T, Janssens A, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385:1873–1883.
   PubMed Web of Science ®Google Scholar
• Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558.
   PubMed Web of Science ®Google Scholar
• Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.
   PubMed Web of Science ®Google Scholar
• Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007;370:230–239.
   PubMed Web of Science ®Google Scholar
• Catovsky D, Fooks J, Richards S. The UK Medical Research Council CLL trials 1 and 2. Nouv Rev Fr Hematol. 1988;30423–427.
   Google Scholar
• Else M, Cocks K, Crofts S, et al. Quality of life in chronic lymphocytic leukemia: 5-year results from the multicenter randomized LRF CLL4 trial. Leuk Lymphoma. 2012;53:1289–1298.
   PubMed Web of Science ®Google Scholar
• Hansen MM, Andersen E, Christensen BE, et al. CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukemia (CLL): preliminary results of a randomized multicenter study. Nouv Rev Fr Hematol. 1988;30:433–436.
   PubMedGoogle Scholar
• Hansen M, Andersen E, Birgens H, et al. CHOP versus chlorambucil + prednisolone in chronic lymphocytic leukemia. Leuk Lymphoma. 1991;5(Suppl):97–100.
   PubMed Web of Science ®Google Scholar
• Kimby E, Björkholm M, Gahrton G, et al. Chlorambucil/prednisone vs. CHOP in symptomatic low-grade non-Hodgkin’s lymphomas: a randomized trial from the Lymphoma Group of Central Sweden. Ann Oncol. 1994;5(Suppl):67–71.
   PubMedGoogle Scholar
• Knauf WU, Lissitchkov T, Aldaoud A, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012;159:67–77.
   PubMed Web of Science ®Google Scholar
• Montserrat E, Alcalá A, Alonso C, et al. A randomized trial comparing chlorambucil plus prednisone vs cyclophosphamide, melphalan, and prednisone in the treatment of chronic lymphocytic leukemia stages B and C. Nouv Rev Fr Hematol. 1988;30:429–432.
   PubMed Web of Science ®Google Scholar
• Morrison VA, Rai KR, Peterson BL, et al. Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: intergroup study cancer and leukemia group B 9011. J Clin Oncol. 2001;19:3611–3621.
   PubMed Web of Science ®Google Scholar
• Mulligan SP, Karlsson K, Strömberg M, et al. Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia. Leuk Lymphoma. 2014;55:2769–2777.
   PubMed Web of Science ®Google Scholar
• Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343:1750–1757.
   PubMed Web of Science ®Google Scholar
• Rai K, Peterson B, Appelbaum F, et al. Long-term survival analysis of the North American Intergroup Study C9011 Comparing fludarabine (F) and chlorambucil (C) in previously untreated patients with chronic lymphocytic leukemia (CLL). Blood. 2009;114:224. In: Abstract 536.
   Web of Science ®Google Scholar
• Raphael B, Andersen JW, Silber R, et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol. 1991;9:770–776.
   PubMed Web of Science ®Google Scholar
• Spriano M, Chiurazzi F, Liso V, et al. Multicentre prospective randomized trial of fludarabine versus chlorambucil and prednisone in previously untreated patients with active B-CLL: final report. Hematol Cell Ther. 2000;42:93.
   Google Scholar
• Travade P. The experience of the French Cooperative Group in the treatment of CLL.. Nouv Rev Fr Hematol. 1990;32:313–317.
   PubMedGoogle Scholar
• Zittoun R, de Witte T. EORTC Leukemia Cooperative Group. A randomized phase II trial of high-dose chlorambucil vs. fludarabine in patients with advanced B-chronic lymphocytic leukemia. Hematol Cell Ther. 1999;41:127–136.
   PubMedGoogle Scholar
• French Cooperative Group on Chronic Lymphocytic Leukemia. Is the CHOP regimen a good treatment for advanced CLL? Results from two randomized clinical trials. Leuk Lymphoma. 1994;13:449–456.
   PubMed Web of Science ®Google Scholar
• Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–5456.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990–4997.
   PubMed Web of Science ®Google Scholar
• Jaksić B, Vitale B. Total tumour mass score (TTM): a new parameter in chronic lymphocyte leukaemia. Br J Haematol. 1981;49:405–413.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bennett JM, Rai KR, et al. Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group. Am J Hematol. 1988;29:152–163.
   PubMed Web of Science ®Google Scholar
• Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials. Haematologica. 2012;97:428–436.
   PubMed Web of Science ®Google Scholar
• Eichhorst BF, Busch R, Schweighofer C, et al. Due to low infection rates no routine anti-infective prophylaxis is required in younger patients with chronic lymphocytic leukaemia during fludarabine-based first line therapy. Br J Haematol. 2007;136:63–72.
   PubMed Web of Science ®Google Scholar
• Morrison VA, Rai KR, Peterson BL, et al. Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an intergroup study, cancer and leukemia group B 9011. J Clin Oncol. 2002;20:3878–3884.
   PubMed Web of Science ®Google Scholar
• Niederle N, Megdenberg D, Balleisen L, et al. Bendamustine compared to fludarabine as second-line treatment in chronic lymphocytic leukemia. Ann Hematol. 2013;92:653–660.
   PubMed Web of Science ®Google Scholar
• Eichhorst B, Fink AM, Bush R, et al. Frontline Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) shows superior efficacy in comparison to Bendamustine (B) and Rituximab (BR) in previously untreated and physically fit patients (pts) with advanced Chronic Lymphocytic Leukemia (CLL): final analysis of an International, Randomized Study of the German CLL Study Group (GCLLSG) (CLL10 Study). 56th American Society of Hematology Annual Meeting and Exposition; December 6–9, 2014; San Francisco, CA. Blood (Suppl). 2014: Abstract 642.
   Google Scholar
• Terasawa T, Trikalinos Na, Djulbegovic B, et al. Comparative efficacy of first-line therapies for advanced-stage chronic lymphocytic leukemia: a multiple-treatment meta-analysis. Cancer Treat Rev. 2013;39:340–349.
   PubMed Web of Science ®Google Scholar
• Cheng MM, Goulart B, Veenstra DL, et al. A network meta-analysis of therapies for previously untreated chronic lymphocytic leukemia. Cancer Treat Rev. 2012;38:1004–1011.
   PubMed Web of Science ®Google Scholar
• Oscier D, Dearden C, Eren E, et al. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia. Br J Haematol. 2012;159:541–564.
   PubMed Web of Science ®Google Scholar
• Ghielmini M, Vitolo U, Kimby E, et al. ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol. 2013;24:561–576.
   PubMed Web of Science ®Google Scholar
• Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–1174.
   PubMed Web of Science ®Google Scholar