High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis.

High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.