Computed tomography scans do not improve the predictive power of 1996 national cancer institute sponsored working group chronic lymphocytic leukemia response criteria.

PURPOSE: National Cancer Institute-sponsored Working Group (NCI-WG) response criteria for chronic lymphocytic leukemia (CLL) rely on physical examination, blood, and bone marrow evaluations. The widespread use of computed tomography (CT) scans has prompted many to advocate for the incorporation of this test into CLL response criteria. PATIENTS AND METHODS: In a retrospective review of 82 CLL patients treated at the Ohio State University (Columbus, OH), we compared CT assessed response using non-Hodgkin's lymphoma (NHL) response definitions with NCI-WG response. RESULTS: Responses by NCI-WG criteria included five complete responses (CRs), 32 partial responses (PRs), 21 patients with stable disease (SD), 17 patients with progressive disease (PD), and seven patients not assessable (NA). Responses by NHL-CT criteria included three CRs, 12 unconfirmed CRs (CRus), 16 PRs, 26 with SD, four with PD, and 21 NA. Using NCI-WG criteria, progression-free survival (PFS) was 27.3 months for CR and 11.4 months for PR. With NHL-CT criteria, PFS was 18.4 months for CR, 11.7 months for CRu, and 14.5 months for PR. In multivariate analysis, both NCI-WG and NHL-CT response correlated with PFS (P = .009 and .001, respectively). CONCLUSION: Current NCI-WG CLL response criteria are a significant predictor of PFS in previously treated CLL patients, with no additional benefit from the inclusion of CT scans. Although retrospective, these results highlight the importance of prospective validation of CT scans before routine inclusion in CLL response criteria.

Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia.

Despite promising preclinical studies with the cyclin-dependent kinase inhibitor flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous clinical trials with this agent have been disappointing. The discovery of differential protein binding of flavopiridol in human and bovine serum contributed to an effective pharmacokinetic-derived schedule of administration of this agent. On the basis of pharmacokinetic modeling using our in vitro results and data from a previous trial, we initiated a phase 1 study using a 30-minute loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks in patients with refractory CLL. A group of 42 patients were enrolled on 3 cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion; cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort 3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of patients with leukocyte counts greater than 200x10(9)/L have made this drug safe to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved a partial response with a median response duration that exceeds 12 months. Responses were noted in patients with genetically high-risk disease, including 5 (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with del(11q22.3). Flavopiridol administered using this novel schedule has significant clinical activity in refractory CLL. Patients with bulky disease and high-risk genetic features have achieved durable responses, thereby justifying further study of flavopiridol in CLL and other diseases.