High-dose sequential chemotherapy with autologous blood stem cell rescue for relapsed or resistant lymphoma

The high-dose sequential regimen developed by Gianni et al. in Milan is a novel concept in which five active drugs are administered sequentially at their maximum tolerated dosages. In previous studies this treatment was efficacious in relapsed Hodgkin's disease and in "de novo" high-risk high-grade NHL. We tested the feasibility, toxicity and efficacy of this approach, administered with simplified supportive measures, as salvage regimen for patients with relapsed (n = 17) or resistant (n = 3) lymphoma (9 high-grade NHL, 4 low-grade NHL and 7 Hodgkin's disease). The regimen included sequential administration of cyclophosphamide (7 g/m2), methotrexate (8 g/m2), etoposide (2 g/m2), mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) over a period of 8 weeks in an effort to reduce hospitalisation to a minimum. Of the 20 initial patients, 15 completed the planned programme. The regimen was subjectively well tolerated despite frequent hospital stays (median 44 days). Recovery of absolute neutrophil and platelet counts after transplantation occurred on the average on days 13 and 11 respectively. A second neutrophil and platelet nadir was seen 7-8 weeks after transplantation. Long-term side effects were a severe stenosing postactinic oesophagitis and a secondary subacute monoblastic leukaemia. At a median follow-up of 24 months, the 2 years disease-free and overall survival are 27% and 60% respectively. Of the 15 patients actually transplanted, 7 (47%) are alive disease-free. Although as feasible and effective as other high-dose regimens, this regimen requires longer hospital stays and its costs may be higher than those of other high-dose programmes.