Tandem high dose chemotherapy for non-hodgkin's lymphoma and hodgkin's disease utilizing cyclophosphamide, etoposide and carboplatin followed by melphalan and carboplatin with autologous stem cell transplantation

Introduction: 48 patients (26 men, 22 women) with relapsed NHL (median age 49 years) and 7 patients (4 men, 3 women) with relapsed HD (median age 37 years) received high dose chemotherapy and autologous stem cell transplantation at Scripps Clinic from February 1995 through January 2000. Regimen: All patients received cyclophosphamide (1500 mg/m²/d x 4d), etoposide (450 mg/m²/d x 4d), and carboplatin (300 mg/m²/d x 4d)(CVCb). Following recovery from this treatment cycle, 23 patients with NHL and 2 patients with HD received melphalan (70 mg/m²/d x 2d) and carboplatin (400 mg/m²/d x 3d)(MCb). Autologous peripheral blood progenitor cells were reinfused after each cycle. Toxicity: No regimen-related mortality was observed. Grade 3 mucositis and grade 2 nausea/ vomiting/diarrhea were the most common toxicities. Two patients experienced grade 4 hepatotoxicity, two patients experienced grade 4 cardiotoxicity, and one patient experienced grade 4 pulmonary toxicity after the CVCb cycle. Grade 4 hepatotoxicity and pulmonary toxicity were seen in two different patients after the MCb cycle. Results: 5/7 HD patients remain alive and free of disease at 48 months. 5/7 patients with low grade NHL are alive, but all have relapsed (median disease free survival, 33 mos; median overall survival, 34 mos). Of 28 patients with intermediate grade NHL, 17 received CVCb, 3 were sensitive induction failures. 11 patients received the additional MCb cycle, 6 were sensitive induction failures. At 48 months, disease-free and overall survivals are 65% and 75% respectively for patients receiving CVCb. Disease-free and overall survivals are 35% at 48 months for patients receiving CVCb plus MCb. The disease-free and overall survival differences between groups were not statistically significant (p=0.14). Conclusions: 1) The CVCb regimen as administered here was well tolerated and no regimen related mortality was noted. 2) For patients with intermediate grade NHL, a second cycle of MCb administered after CVCb did not improve disease free or overall survival. 3) The CVCb regimen is effective therapy for the small number of HD patients treated. A larger number of patients would be needed to assess the impact of a second MCb cycle on outcomes.