Overview of the treatment of chronic lymphocytic leukemia
- Kanti R Rai, MD
Kanti R Rai, MD
- Professor of Medicine and Molecular Medicine
- Hofstra North Shore-LIJ School of Medicine at Hofstra University
- Stephan Stilgenbauer, MD
Stephan Stilgenbauer, MD
- Professor of Medicine
- Ulm University
Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). It is characterized by a progressive accumulation of functionally incompetent lymphocytes, which are usually monoclonal in origin.
CLL is considered to be identical (ie, one disease with different manifestations) to the mature (peripheral) B cell neoplasm small lymphocytic lymphoma (SLL), one of the indolent non-Hodgkin lymphomas. The term CLL is used when the disease manifests primarily in the blood, whereas the term SLL is used when involvement is primarily nodal. While there is some difference to the treatment of early stage CLL and SLL, the treatment of advanced stage disease is the same. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia".)
General issues regarding the treatment of CLL/SLL will be reviewed here. Further details regarding the selection of initial therapy for advanced stage or symptomatic disease, the treatment of relapsed/refractory disease, the use of hematopoietic cell transplantation, and the management of complications of CLL/SLL and its treatment are discussed separately. (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia" and "Treatment of relapsed or refractory chronic lymphocytic leukemia" and "Hematopoietic cell transplantation in chronic lymphocytic leukemia" and "Overview of the complications of chronic lymphocytic leukemia".)
The pathophysiology, clinical manifestations, diagnosis, staging, and prognosis of CLL and SLL are also discussed separately. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia" and "Staging and prognosis of chronic lymphocytic leukemia" and "Pathophysiology and genetic features of chronic lymphocytic leukemia".)
INDICATIONS FOR TREATMENT
Not all patients with CLL require treatment at the time of diagnosis. This is principally because:
- Effects of chlorambucil and therapeutic decision in initial forms of chronic lymphocytic leukemia (stage A): results of a randomized clinical trial on 612 patients. The French Cooperative Group on Chronic Lymphocytic Leukemia. Blood 1990; 75:1414.
- Montserrat E, Vinolas N, Reverter JC, et al. Chronic lymphocytic leukemia in early stage "smoldering" and "active" forms in chronic lymphocytic leukemia. In: Scientifc Advances and Clinical Developments, Cheston BD (Ed), Marcel Decker, New York 1993. p.281.
- Natural history of stage A chronic lymphocytic leukaemia untreated patients. French Cooperative Group on Chronic Lymphocytic Leukaemia. Br J Haematol 1990; 76:45.
- Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials. CLL Trialists' Collaborative Group. J Natl Cancer Inst 1999; 91:861.
- Del Giudice I, Chiaretti S, Tavolaro S, et al. Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases. Blood 2009; 114:638.
- Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975; 46:219.
- 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.
- Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. International Workshop on Chronic Lymphocytic Leukemia. Ann Intern Med 1989; 110:236.
- Binet JL, Caligaris-Cappio F, Catovsky D, et al. Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia. Blood 2006; 107:859.
- 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.
- Gribben JG. How I treat CLL up front. Blood 2010; 115:187.
- Molica S, Alberti A. Prognostic value of the lymphocyte doubling time in chronic lymphocytic leukemia. Cancer 1987; 60:2712.
- Montserrat E, Sanchez-Bisono J, Viñolas N, Rozman C. Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance. Br J Haematol 1986; 62:567.
- Pepper C, Majid A, Lin TT, et al. Defining the prognosis of early stage chronic lymphocytic leukaemia patients. Br J Haematol 2012; 156:499.
- Morrison WH, Hoppe RT, Weiss LM, et al. Small lymphocytic lymphoma. J Clin Oncol 1989; 7:598.
- Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2016; 127:208.
- Thompson PA, Tam CS, O'Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood 2016; 127:303.
- Blum KA, Young D, Broering S, et al. Computed tomography scans do not improve the predictive power of 1996 national cancer institute sponsored working group chronic lymphocytic leukemia response criteria. J Clin Oncol 2007; 25:5624.
- Keller JW, Knospe WH, Raney M, et al. Treatment of chronic lymphocytic leukemia using chlorambucil and prednisone with or without cycle-active consolidation chemotherapy. A Southeastern Cancer Study Group Trial. Cancer 1986; 58:1185.
- Nabhan C, Coutré S, Hillmen P. Minimal residual disease in chronic lymphocytic leukaemia: is it ready for primetime? Br J Haematol 2007; 136:379.
- INDICATIONS FOR TREATMENT
- Asymptomatic early stage
- Symptomatic or advanced stage
- MANAGEMENT OF CLL/SLL
- Management of asymptomatic CLL
- Treatment of localized SLL
- Treatment of symptomatic CLL or advanced SLL
- - Pre-treatment evaluation
- - Selection of therapy
- Management of the complications of CLL and its therapy
- EVALUATING RESPONSE TO TREATMENT
- DURATION OF THERAPY
- RELAPSED DISEASE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS