Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Evaluating response to treatment of chronic lymphocytic leukemia

Kanti R Rai, MD
Stephan Stilgenbauer, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Rebecca F Connor, MD


Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms) characterized by a progressive accumulation of a usually monoclonal population of functionally incompetent lymphocytes. CLL is considered to be identical (ie, one disease with different manifestations) to the mature (peripheral) B cell neoplasm small lymphocytic lymphoma (SLL). The term CLL is used when the disease manifests primarily in the bone marrow and blood, while the term SLL is used when involvement is primarily nodal (ie, absolute B lymphocyte count in the peripheral blood <5000/microL [5 x 109/L]). (See "Classification of the hematopoietic neoplasms" and "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia".)

Treatment is indicated when there are disease-related symptoms or evidence of progression (ie, "active disease" (table 1)). Except for allogeneic hematopoietic cell transplantation (HCT), treatment options for CLL are not curative. The International Workshop Group on CLL (IWCLL) published a revised version of the guidelines for evaluating disease response that were published in 1996 by the National Cancer Institute Working Group (NCI/WG) (table 2) [1-3]. These efforts in developing standardized criteria for the evaluation of response have also allowed comparison of results from different therapeutic trials.

The response evaluation and criteria will be reviewed here. The initial treatment of CLL/SLL, the treatment of relapsed or refractory disease, and the management of the complications of CLL are discussed separately. (See "Overview of the treatment of chronic lymphocytic leukemia" and "Treatment of relapsed or refractory chronic lymphocytic leukemia" and "Overview of the complications of chronic lymphocytic leukemia".)


Patients should be evaluated before each treatment cycle to determine how their disease is responding to therapy. The specific evaluation performed to assess the response to therapy differs depending upon whether the patient is enrolled in a therapeutic research protocol (clinical trial) or is being treated in general practice [3]:

For those treated in general practice, response evaluation should always include a history, physical examination, and complete blood count with differential. The history should include questions regarding constitutional symptoms such as unintentional weight loss, fatigue, fevers, and night sweats. The physical examination should pay particular attention to the evaluation of lymphadenopathy, hepatomegaly, and splenomegaly.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jan 10, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. 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.
  2. Chronic lymphocytic leukemia: recommendations for diagnosis, staging, and response criteria. International Workshop on Chronic Lymphocytic Leukemia. Ann Intern Med 1989; 110:236.
  3. 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.
  4. Eichhorst BF, Fischer K, Fink AM, et al. Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis. Blood 2011; 117:1817.
  5. Cheson BD, Byrd JC, Rai KR, et al. Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol 2012; 30:2820.
  6. Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med 1995; 333:1052.
  7. Rawstron AC, Kennedy B, Evans PA, et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001; 98:29.
  8. Maloum K, Sutton L, Baudet S, et al. Novel flow-cytometric analysis based on BCD5+ subpopulations for the evaluation of minimal residual disease in chronic lymphocytic leukaemia. Br J Haematol 2002; 119:970.
  9. Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood 2016; 127:279.
  10. Kovacs G, Robrecht S, Fink AM, et al. Minimal Residual Disease Assessment Improves Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia (CLL) Who Achieve Partial Response: Comprehensive Analysis of Two Phase III Studies of the German CLL Study Group. J Clin Oncol 2016.
  11. Böttcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol 2012; 30:980.
  12. Strati P, Keating MJ, O'Brien SM, et al. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL. Blood 2014; 123:3727.
  13. Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol 2006; 24:5343.
  14. Smith DD, Goldstein L, Cheng M, et al. Modeling absolute lymphocyte counts after treatment of chronic lymphocytic leukemia with ibrutinib. Ann Hematol 2015; 94:249.
  15. Herman SE, Niemann CU, Farooqui M, et al. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study. Leukemia 2014; 28:2188.
  16. Rossi D, Gaidano G. Lymphocytosis and ibrutinib treatment of CLL. Blood 2014; 123:1772.
  17. Woyach JA, Smucker K, Smith LL, et al. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. Blood 2014; 123:1810.