PHILADELPHIA-The addition of rituximab(Drug information on rituximab) (Rituxan) to the standard cyclophosphamide(Drug information on cyclophosphamide), doxorubicin(Drug information on doxorubicin), vincristine (Oncovin), and prednisone(Drug information on prednisone) (CHOP) regimen improves duration of response and eventfree survival in patients with aggressive non-Hodgkin's lymphoma. Although the mechanism of action of rituximab in combination with CHOP (R-CHOP) has not been fully elucidated, it has been hypothesized that rituximab-mediated apoptosis may be enhanced during chemotherapy. Two reports at the American Society of Hematology 2002 Annual Meeting examined the efficacy of RCHOP in patients with aggressive or poor-prognosis lymphoma. Overcoming Resistance Expression of the bcl-2 protein is associated with poor prognosis in patients with diffuse large B-cell lym- phoma (DLBCL) because bcl-2 protein overexpression makes cancer cells resistant to chemotherapy-induced apoptosis. In a study performed by the Groupe d'Etude des Lymphomes de l'Adulte (GELA) in France, investigators have demonstrated the efficacy and safety of R-CHOP in elderly patients with DLBCL. To assess the effect of rituximab on bcl-2-associated disease failure, Nicolas Mounier, MD, PhD, and fellow GELA investigators analyzed bcl-2 expression and clinical outcome from the GELA study (ASH abstract 603). Patients ranged in age from 60 to 80 years, had previously untreated DLBCL, and were randomized to receive standard CHOP or CHOP plus concurrent rituximab (375 mg/m2). The status of bcl-2 protein expression was available for 292 patients with histologically reviewed DLBCL; 193 patients (66%) were bcl-2 positive and 99 patients (34%) were bcl-2 negative. A comparison of baseline patient characteristics and prognostic factors including bcl-2 status indicated that the two groups were similar. The response rates for patients according to bcl-2 status and treatment arm are summarized in Table 1. Response rates, overall survival, and event-free survival were improved with R-CHOP compared with CHOP alone in patients who were bcl-2 positive.[ 2] Furthermore, multivariate analysis confirmed that R-CHOP provided a significant survival benefit in patients who were bcl-2 positive over patients that were bcl-2 negative. These results have since been published.[ 3] The investigators concluded that rituximab overcomes bcl-2-dependent resistance to chemotherapy and recommended further evaluation of R-CHOP in younger patients with DLBCL. R-CHOP Long-Term Follow-up Long-term follow-up data on RCHOP as front-line therapy for patients with aggressive non-Hodgkin's lymphoma was reported by Julie Vose, MD, of the Nebraska University Medical Center in Omaha (ASH abstract 1396). Thirty-three patients were treated. Patient characteristics are summarized in Table 2. In the initial report of this study, the overall response rate was 94% after a median follow-up of 26 months and approximately two thirds of patients achieved a complete response.[ 5] In the more recent report, after a median follow-up of 62 months, 88% of patients are alive and 82% (27 of 33 patients) have not progressed. Figure 1 shows time to disease progression or death at 60 months or greater following treatment. Two patients with an International Prognostic Index (IPI) score of 0 or 1 have relapsed and four patients with an IPI score greater than or equal to 2 have relapsed. Four of the relapsing patients died and two were salvaged with chemotherapy and/or stem cell transplantation. No additional long-term complications have been reported during this follow-up period. Therefore, Dr. Vose concluded that R-CHOP is a safe and effective front-line treatment for patients with aggressive non-Hodgkin's lymphoma.