Chronic Lymphocytic Leukemia
Pathophysiology/Epidemiology
Clinical staging of chronic lymphocytic leukemia.
Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS.
Blood. 1975;46:219-234.
Description: Proposed clinical staging as a predictor of survival.
PubMed citation number: 1139039
A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis.
Binet JL, Auquier A, Dighiero G, et al.
Cancer. 1981;48:198-206.
Description: Cox multivariate analysis of survival identifying prognostic factors at diagnosis.
PubMed citation number: 7237385
The American College of Surgeons Commission on Cancer and the American Cancer Society: the National Cancer Data Base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia.
Diehl LF, Karnell LH, Menck HR.
Cancer. 1999;86:2684-2692.
Description: Uses the National Cancer Data Base to describe the epidemiology of CLL between 1985 and 1995.
PubMed citation number: 10594864
Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia.
Damle RN, Wasil T, Fais F, et al.
Blood. 1999;94:1840-1847.
Description: Unmutated Ig V gene status correlates with increased expression of p38, and may indicate a less mature CLL phenotype. Both markers correlate with poor response to treatment and shorter survival.
PubMed citation number: 10477712
Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia.
Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK.
Blood. 1999;94:1848-1854.
Description: Established that survival was significantly worse for patients with unmutated VH genes irrespective of stage.
PubMed citation number: 10477713
Genomic aberrations and survival in chronic lymphocytic leukemia.
Dohner H, Stilgenbauer S, Benner A, et al.
N Engl J Med. 2000;343:1910-1916.
Description: A correlative study defining prognostic subsets of CLL patients based upon karyotypic abnormalities. It established 13q as the most common deletion in CLL, with the longest median survival. 17p deletions had the shortest median survival. Normal karyotype and 12p trisomy correlated with an intermediate median survival.
PubMed citation number: 11136261
ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia.
Rassenti LZ, Huynh L, Toy TL, et al.
N Engl J Med. 2004;351:893.
Description: Zap 70 expression is an independent adverse prognostic marker in CLL.
PubMed citation number: 15329427
Treatment
National Cancer Institute–sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment.
Cheson BD, Bennett JM, Grever M, et al.
Blood. 1996;87:4990-4991.
Description: Guidelines for treatment.
PubMed citation number: 8652811
Multicentre prospective randomized trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia.
Johnson S, Smith AG, Loffler H, et al: The French Cooperative Group on CLL.
Lancet. 1996;347:1432-1438.
Description: Single versus combined modality therapy.
PubMed citation number: 8676625
Chlorambucil in indolent chronic lymphocytic leukemia: French Cooperative Group on Chronic Lymphocytic Leukemia.
Dighiero G, Maloum K, Desablens B, et al.
N Engl J Med. 1998;338:1506-1514.
Description: Two randomized clinical trials testing deferment of therapy until disease progression.
PubMed citation number: 9593789
Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia: a randomized, controlled clinical trial.
Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia.
N Engl J Med. 1988;319:902-907.
Description: Eighty-four patients with CLL and hypogammaglobulinemia or history of infection were randomized to IVIG every 3 weeks for 1 year versus placebo injection. Bacterial infections were decreased by half in the IVIG group.
PubMed citation number: 2901668
Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials.
CLL Trialists’ Collaborative Group.
J Natl Cancer Inst. 1999;91:861-868.
Description: Meta-analysis comparing the effects of survival on immediate versus deferred therapy and combination versus single-agent therapy as first-line treatment for advanced disease.
PubMed citation number: 10340906
Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features.
Mauro FR, Foa R, Cerretti R, et al.
Blood. 2000;95:2786-2792.
Description: In this single-institution retrospective study, 4.3% of 1203 patients with CLL developed AHA, regardless of treatment used.
PubMed citation number: 10779422
Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia.
Rai KR, Peterson BL, Appelbaum FR, et al.
N Engl J Med. 2000;343:1432-1438.
Description: Showed fludarabine has a better response rate and duration of response than chlorambucil. No difference in overall survival.
PubMed citation number: 11114313
Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.
Huhn D, von Schilling C, Wilhelm M, et al: German Chronic Lymphocytic Leukemia Study Group.
Blood. 2001;98:1326-1331.
Description: This phase 2 study demonstrated a 50% reduction in circulating lymphocytes in 45% of relapsed/refractory patients treated with 4 weekly doses of rituximab.
PubMed citation number: 11520778
Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.
Leporrier M, Chevret S, Cazin B, et al: French Cooperative Group on Chronic Lymphocytic Leukemia.
Blood. 2001;98:2319-2325.
Description: Showed no difference in overall survival between ChOP and fludarabine, but increase in clinical remission rate and a trend toward a better tolerance of fludarabine over CHOP.
PubMed citation number: 11588025
Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study.
Keating MJ, Flinn I, Jain V, et al.
Blood. 2002;99:3554-3561.
Description: Found a 33% response rate to alemtuzumab in 93 patients with refractory or relapsed CLL who had received prior alkylator and fludarabine therapy.
PubMed citation number: 11986207
Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia.
Weiss MA, Maslak PG, Jurcic JG, et al.
J Clin Oncol. 2003;21:1278-1284.
Description: Small phase 2 trial showing a 74% response rate to pentostatin and cyclophosphamide in relapsed/refractory CLL patients.
PubMed citation number: 12663715
Review
Allogeneic and autologous transplantation for chronic lymphocytic leukemia.
van Besien K, Keralavarma B, Devine S, Stock W.
Leukemia. 2001;15:1317-1325.
Description: Review of the literature.
PubMed citation number: 11516091