8123 Background: The high-dose sequential (HDS) chemotherapy approach, including early dose-intensification and autograft with peripheral blood progenitor cells (PBPC), was introduced several years ago (Gianni & Bonadonna, 1989); subsequently, it has been broadly used in the management of both non-Hodgkin s (NHL) and Hodgkin s Lymphoma (HL). The outcome of a large series of lymphoma patients treated with the HDS approach at 10 GITIL Centers is reported. Methods: Data have been collected on 1,266 patients, who received either the original or slightly modified HDS regimens. There were 213 HL and 1,053 NHL (630 intermediate/high-grade, 423 low-grade); median age was 46 yrs. Overall, 671 (53%) patients had refractory/relapsed disease, 595 (47%) were at diagnosis. Most patients were autografted with PBPC; 158 (12%) patients did not undergo autografting due to toxicity, disease progression or poor harvests. Results: Overall, 1,013 (80%) patients reached Complete Remission (CR) following HDS. As to December 2006, 93 (7%) patients died for early/late toxicities, 328 (26%) died for lymphoma, 844 are known to be alive. At a lead follow-up of 18 years, and a median follow-up of 5 yrs, the 5-yr Overall Survival (OS) projection is 64% (S.E.: 2%). The long-term survival was quite favorable in patients achieving a Complete Remission (CR), with a 5-yr OS projection of 76%. The prolonged OS in patients achieving CR was consistent in all lymphoma subtypes, i.e. both low and high-grade NHL (5-yr OS: 77% in both), and HL (5-yr OS: 72%). Patients at diagnosis had a significantly better outcome compared to patients treated for relapsed/refractory disease, again CR achievement was associated with prolonged survival in both subgroups (82% and 69%, respectively, at 5 yrs.). On multivariate Cox survival analysis, CR achievement was the most powerful predictor of long-term survival (HR 0.13, c.i.: 0.10–0.17). Lastly, achieving substantial tumor reduction before autografting had a major influence on the clinical outcome. Conclusions: 1. the HDS program is feasible in a multicenter setting; 2. the long-term outcome is well influenced by the CR status after HDS; 3. the influence of CR achievement on the long-term survival holds true in all lymphoma subtypes, including indolent lymphomas; 4. an adequate pre-autograft tumor debulking may contribute to a favorable long-term outcome. [Table: see text]
Long-term complete remission of a patient with high grade neuroendocrine carcinoma of ampulla of Vater