Sequential chemotherapy and late intensification for malignant lymphomas of aggressive histologic type

Fifty-six patients with malignant lymphoma of aggressive histologic type (51 large cell, three diffuse undifferentiated, and two nodular mixed) were treated with three non-cross-resistant combination chemotherapy regimens that were introduced sequentially according to the response to therapy. The objective was to increase the complete remission rate by changing the chemotherapy regimen early if the patient did not attain a complete remission after three courses of treatment. Late intensification was also used with the aim of prolonging the duration of complete remission. The overall complete remission rate obtained with this approach was 82 percent (100 percent in stages I to III and 66 percent in stage IV). The projected survival at four years is 71 percent (93 percent for stages I to III and 55 percent for stage IV). Eighty percent of patients with complete remission are projected to have continued remission at four years. Compared with previous experience with Adriamycin-based combination regimens, these results represent an improvement in remission and survival parameters. The most significant gains occurred in the prolongation of survival of patients with stages I to III disease and in the improved duration of complete remission of patients with stage IV disease. Toxicity included 15 documented infections among 320 courses of therapy, four cases of congestive heart failure, one case of bleomycin lung toxicity, and two cases of liver dysfunction. This multiple combination regimen represents an improvement over previous results utilizing Adriamycin-based combination chemotherapy.