High dose chemotherapy without hematopoietic cell support for the treatment of refractory lymphoma

Conventional dose combination chemotherapy for patients with relapsed or re fractory lymphoma is rarely curative. High dose chemotherapy followed by he matopoietic progenitor cell transplant (HPCT) has a clearly defined role in patients who have first relapsed after standard CHOP chemotherapy for lymp homa. However, the role of HPCT is less well defined for patients with chem o-resistant, or chemo-refractory disease. Sixteen patients (15 Non-Hodgkin' s, 1 Hodgkin's Disease) were entered into a phase II study to determine if a dose intensive induction regimen in heavily pre-treated refractory lympho ma patients could permit further consolidation with HPCT. The primary endpo ints were survival, response, toxicity and resource utilization. The regime n consisted of continuous infusion etoposide 1 or 2 gm/m(2)/72 hours, idaru bicin 12mg/m(2)/d far 3 days followed by cytarabine 2gm/m(2)/72 hours on da ys 8,9, and 10 (VIC). Fifteen patients were evaluable for objective respons e. The overall response rate was 53% with 7 patients achieving a partial re sponse and 1 patient achieving a complete response. Of the 8 responders, 6 patients subsequently received high dose chemotherapy followed by HPCT (4 a utologous, 2 allogeneic). The median survival was 176 days for the non-resp onders contrasted with 722 days for the responders. The average duration of hospitalization was 38 days. Toxicity was mainfest primarily as mucositis with a median grade of 3 among the first 13 patients, and a median grade of 2 in three subsequent patients who received an etoposide dose of 1gm/m(2)/ 72 hours. All patients had an episode of neutropenic fever and 5 patients d eveloped clinically significant pneumonitis during therapy. The VIC regimen is active in the treatment of chemo-refractory lymphoma wit h clinically significant differences in survival for patients who respond t o therapy. Further modifications to the regimen could include the addition of a topoisomerase I inhibitor for synergy with etoposide, and using VIC as part of a tandem transplant regimen where response to VIC would allow furt her therapy with a myeloablative induction followed by HPCT.