Is CHOP the standard of therapy for poor-prognosis large-cell lymphoma?

The best therapy for advanced large-cell lymphoma is unknown since among the current chemotherapeutic programs no single regimen has emerged with therapeutic superiority and tolerable toxicity. In a study by Fisher, data were derived from the prospectively randomized trial of the Southwest Oncology Group (SWOG) which compared CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) to m-BACOD, ProMACECytabom, and MACOP-B [1]. The case for more aggressive cytotoxic therapy has been made by Gianni et al. using data from a trial comparing MACOP-B to an extended program of chemotherapy administration followed by high-dose therapy and autotransplantation [2]. In both series, patients with classic large-cell lymphoma were included, but not all patients were in the high-risk prognostic group based on the widely accepted International Prognostic Index. In fairness, Dr. Fisher does not advocate CHOP as the treatment of choice per se but rather emphasizes the need for clinical trials of new and, if necessary, more intensive treatment for large-cell lymphoma since more than 60% of the patients in the SWOG trial have relapsed on long-term follow-up. Clearly, regimens developed in single institutions with a high order of selectivity, especially leaning to younger patients with favorable prognostic features, do not offer more than CHOP, which, if nothing else, is relatively straightforward in design and schedule. Of course, the potential negative spin-off of this trial is that patients with largecell lymphoma are not referred for innovative treatment programs because CHOP can be easily given in a community setting. The SWOG trial emphasized how poor the outcome of CHOP and other regimens can be with adequate follow-up, with less than 50% cured. The International Prognostic Index study emphasized that poor prognostic patients had a 20%-30% five-year disease-free survival [3]. The benefits of CHOP and/or other similar modified regimens are directly proportional to clinical prognostic factors outlines in the International Prognostic Index. For poor-prognosis patients, clearly, new treatments are needed. In a study by Gianni, data were derived from a protracted randomized comparison of MACOP-B to his high-dose alternative following sequential use of active agents prior to ABMT (unpublished data). The data are interesting and, although based on relatively small numbers, show a superiority for the more intensive arm. While this is not a definitive study, it does suggest that dose intensification might offer a measurable advantage to some patients in the poor-prognosis groups. This is further suggested by the GELA Group study which compared early intensification with autologous transplantation (ABMT) and high-dose therapy with combination chemotherapy alone in patients who have achieved an initial complete remission [4]. A follow-up of that data has shown an emerging significant advantage to patients in the high-risk group (International Prognostic Index) who received early intensification. The large numbers of patients in the other prognostic groups in the trial did not derive a survival benefit from early ABMT once a complete remission was achieved. This suggests that in the more favorable groups, failure and subsequent death are less than in higher risk groups but, in the latter, are more likely due to drug resistance which cannot be overcome by ABMT. In contrast, patients in the high-risk prognostic group showed a lower complete remission rate and a