Toxicity of high-dose sequential chemotherapy and purged autologous hematopoietic tell transplantation precludes its use in refractory/recurrent non-Hodgkin's lymphoma

We conducted a pilot study in 20 patients with high-risk or recurrent/refra ctory non-Hodgkin's Lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cyto reduction with standard salvage therapy, HDSC/AHCT was administered in 4 ph ases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m (2) followed by granulocyte colony-stimulating factor (G-CSF) at 10 mug/kg per day and leukayheresis upon recovery from white blood cell nadir. The he matopoietic cell product was enriched by Percoll gradient separation and pu rged with a B-cell or T-cell monoclonal antibody panel and complement. Phas e 2 consisted of methotrexate 8 g/m(2) with leucovorin rescue and vincristi ne 1.4 mg/m(2). Phase 3 was etoposide 2 g/m(2) with G-CSF 5 mug/kg per day. In phase 1, the preparative regimen of mitoxantrone 60 mg/m(2) and melphal an 180 mg/m(2) was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell -rich B-cell, lymphoblastic, and peripheral T cell. The remission status wa s first partial remission (PR1; n = 1) or beyond first complete remission ( post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase be cause of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), acid chronic active hepatitis C (n = 1 ), Treatment-related toxicities in the remaining 11 transplant recipients w ere car diomyopathy, hemorrhagic cystitis, persistent cytopenias, acute ren al failure, abnormal liver function test results, and infectious complicati ons. There were no treatment-related deaths. Eight of the 11 transplant rec ipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall surviv al was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is assoc iated with considerable acute and chronic toxicities. Given the toxicity pr ofile, efficacy data were not sufficiently promising to warrant further stu dy.