2-Chlorodeoxyadenosine (2-CDA) therapy in previously untreated patients with follicular stage III-IV non-Hodgkin's lymphoma

iInstitute of Pathology, Summary Purpose: This phase II multi-institutional trial was designed to assess response and toxicity of 2-chlorodeoxy adenosine (2-CDA) in patients with previously untreated follicular lym- phoma. The clinical significance of detecting cells carrying the t(14;18) translocation (bcl-2/JH rearrangement) in pe- ripheral blood and bone marrow by polymerase chain reac- tion (PCR) before, during and after treatment was also exam- ined. Patients and methods: Between May 1993 and October 1995, 37 patients were accrued: male/female: 15/22, median age 51 years (range: 20-78), stage TH/TV: 9/28. Patients re- ceived a total 2-CDA dose of 0.7 mg/kg as continuous s.c. or i.v. infusions over 7 days, every 28 days for a maximum of 5 cycles. A total of 165 cycles were administered. In 25 pa- tients, blood and bone marrow before, during and after treat- ment were available for PCR analysis of the bcl-2/JH re- arrangements. Results: All 37 patients were evaluable for response and toxicity. The overall response rate was 84% (95% confidence interval, 68%-94%) with 14% CR (n - 5) and 70% PR (n - 26) and a median time to treatment failure of 15.7 months. bcl-2/JH rearrangement in peripheral blood and/or bone marrow was found in 10/25 of patients (40%) before treat- ment and 5 of these became repeatedly negative after 2-CDA therapy. There was no apparent association between bcl-2/ JH result and response. In 11 patients, 2-CDA was stopped because of progressive disease (n — 4), myelotoxicity (grade 2-3, n = 4), and other causes (n — 3, pulmonary embolism, metabolic disorder, and patient's decision). Four patients (11%) suffered from infections (grade 2-3). In 6 patients, persistent thrombocytopenia of 7.5 months (range: 3-21) occurred after completion of the 5 cycles. Conclusion: 2-CDA is active in untreated follicular lym- phomas, but time to treatment failure suggests no advantage compared with standard treatment and toxicity on haemato- poietic stem cells appears to be more pronounced. Molecular remission is induced in a considerable proportion of patients with disappearance of the bcl-2/JH rearrangement, and its possible significance as a predictive factor for quality of re- sponse and relapse warrants further study.