INTENSIVE SEQUENTIAL CHEMOTHERAPY WITH REPEATED BLOOD STEM-CELL SUPPORT FOR UNTREATED POOR-PROGNOSIS NON-HODGKINS-LYMPHOMA

Purpose: To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensif ied cycles supported by stem-cell infusion in high-risk and high-inter mediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. Patients and Methods: A pilot nonrandomized study included 20 untreated patien ts aged less than 60 years with aggressive histologically identified N HL and two or three adverse-prognosis criteria (International Index). patients received an ambulatory regimen with high-dose chemotherapy su pported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 year s (range, 20 to 59), with 13 men and seven women. Chemotherapy consist ed of one cycle every 21 days for a total of six cycles. The first thr ee cycles (Al, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg /m(2), doxorubicin (Doxo) 75 mg/m(2), and vincristine 2 mg (plus corti costeroids). The last three cycles (B4, B5, and B6) consisted of the s ame drug combination plus etoposide 300 mg/m(2) and cisplatin 100 mg/m (2). For an expected duration of 18 weeks, the projected dose-intensit y was 25 mg/m(2)/wk for Doxo and 1,000 mg/m(2)/wk for Cy. G-CSF 300 pg was administered from day 6 following each cycle until neutrophil rec onstitution. Two aphereses were performed at approximately day 13 afte r each A cycle, and PBSCs were injected at day 4 of each B cycle. Radi otherapy on tumor masses greater than or equal to 5 cm was scheduled a fter completion of the lost cycle. Results: The median duration of gra de 4 neutropenia was 1 day(range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of gr ade 4 thrombopenia wets 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during c ycles A and 8, respectively (P < .01). Only three patients did not com plete the protocol: one due to emergency surgery after cycle B4, one w ho died after cycle B5 from interstitial pneumonia, and one with delay ed hematologic reconstitution after cycle B4. Chemotherapy delivery wa s optimal (median actual relative dose-intensity, 97%; range, 66 to 10 0). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg eto poside (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300), Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), a nd one toxic death. With a median follow-up period of 25 months (range , 16 to 43), 15 patients are alive, with 12 in continuous first CR; fi ve patients relapsed (four of four PRs and one of 13 CRs). Two-year su rvival and failure-free survival (FFS) rates are 73% and 56%, respecti vely. The disease-free survival (DFS) rate for the CRs is 86%. Conclus ion: PBSC support contributes to the feasibility of first-line, very-h igh-dose, ambulatory chemotherapy delivery in poor-risk NHL and is ass ociated with a high rate of remission and FFS. (C) 1997 by American So ciety of Clinical Oncology.