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 i s a novel concept in which five active drugs are administered sequenti ally at their maximum tolerated dosages. In previous studies this trea tment was efficacious in relapsed Hodgkin's disease and in ''de novo'' high-risk high-grade NHL. We tested the feasibility, toxicity and eff icacy of this approach, administered with simplified supportive measur es, as salvage regimen for patients with relapsed (n = 17) or resistan t (n = 3) lymphoma (9 high-grade NHL, 4 low-grade NHL and 7 Hodgkin's disease). The regimen included sequential administration of cyclophosp hamide (7 g/m(2)), methotrexate (8 g/m(2)), etoposide (2 g/m(2)), mito xantrone (60 mg/m(2)) and melphalan (180 mg/m(2)) over a period of 8 w eeks in an effort to reduce hospitalisation to a minimum. Of the 20 in itial patients, 15 completed the planned programme. The regimen was su bjectively well tolerated despite frequent hospital stays (median 44 d ays). Recovery of absolute neutrophil and platelet counts after transp lantation occurred on the average on days 13 and 11 respectively. A se cond neutrophil and platelet nadir was seen 7-8 weeks after transplant ation. Long-term side effects were a severe stenosing postactinic oeso phagitis and a secondary subacute monoblastic leukaemia. At a median f ollow-up of 24 months, the 2 years disease-free and overall survival a re 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.