National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment

N 1988, THE National Cancer Institute-sponsored Working Group (NCI-WC) on chronic lymphocytic leukemia (CLL) published guidelines for the design and conduct of clinical trials in CLL with two major objectives: first, to facilitate comparisons of results of clinical trials in CLL by providing standardized eligibility, response, and toxicity criteria; and, second, to encourage a framework on which to evaluate new scientific studies related to our increasing understanding of the biology and immunology of this disease.' These guidelines were rapidly adopted by the majority of the clinical trials community, and were also used by the Food and Drug Administration during its evaluation process for the approval of fludarabine. The differences between these guidelines and those subsequently published by the International Working Group on CLL (IWCLL), which were general-practice recommendations' are listed in Table 1. For diagnosis, the NCI-WC requires a lymphocyte count of 5 X loy& which is lower than the 10 X 109/L required by the IWCLL, unless the lymphocytes are B cells and the bone marrow is involved. To be considered a complete remission (CR), the NCI-WC criteria specify that less than 30% lymphocytes must be present in the bone marrow, with a recommendation that the clinical significance of lymphoid nodules be assessed prospectively (Table 1); the IWCLL allows focal infiltrates or nodules in the bone marrow aspirate and biopsy for CR. The IWCLL uses a shift in clinical stage as the sole index of partial remission (PR), whereas the NCI-WC provides more specific criteria and recommends validation of the relevance of stage shift. The major differences were the well-defined criteria in the NCI guidelines regarding when to initiate therapy, hematologic toxicity, and other important components for clinical trials design. The purpose of this report is to present those revisions as considered necessary in view of advances in the past 8 years. Many of these revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and, also, with the experience following the use of newer, more effective agents, such as fludarabine.' Although this report will focus on those changes recommended by the NCI-sponsored CLL Working Group, it will include sufficient details from the original guidelines so that the reader would find it a complete document by itself without having to refer to the older version.