Brazilian Experience Using High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Relapse/Refractory Aggressive Non-Hodgkin Lymphoma (NHL).

Abstract

The purpose of this study was to evoluate the use of high dose cyclophosphamide HD (CY) 7 or 4g/m2 and HD etoposide (VP-16) 2g/m2 followed by AHSCT in patients affected by aggressive NHL. From January 1998 to November 2006, 106 patients, 66 males, 40 females, median age 47 (8–66) years underwent into this regimen. The diagnosis was 83 (78.3%) DLBCL, 13 (12.3%) with T-cell Lymphoma and 10 (9.4%) Mantle Cell. At diagnosis, 88 (83%) were stage III or IV, 34 (32.1%) presented bone marrow involvement, 65 (61.3%) bulky disease, 67 (63.2%) B symptoms and 45 (42.5%) were high or high intermediate risk according to IPI. Prior to HDCY patients had been submitted to a mean of 2 (1–3) therapy lines and 6 (5.7%) were in complete remission (CR), 38 (35.8%) partial remission (PR), 62 (58.5%) disease progression (PD) or relapse. Concerning CY dose 42 (39.6%) patients received 4 g/m2 and 64 (60.4%) 7 g/m2, respectively. After HDS, 13 (31%) patients who had used 4 g/m2 and 30 (47%) used 7 g/m2 were in CR (P= 0.03). After the HDCY 43 (40.6%) were in CR, 33 (31.1%) PR, 21 (19.8%) remained in PD and 9 (8.5%) died. After a median follow-up of 4.1 (1.5–57) months, 80 patients (75.5%) were submitted to AHSCT and their present status is 44 alive [33 CR, 4 PR, 7 PD]; 36 dead [4 CR, 1 PR, 2 relapse, 17 PD and 12 had death related to procedure]. Their overall survival was 45% in 8 years. Currently we have 50/106 (47%) alive patients, 35 CR, 6 PR and 9 PD. Overall Survival (OS) was 37%, Disease Free Survival (DFS) 49%, Progression Free Survival (PFS) 42%, Event Free Survival (EFS) 28%. OS by diagnosis was 42% DLBCL, 40% T-cell in 8 years whereas 20% Mantle Cell in 6 years (P=NS). OS by B symptoms patients was 22% versus 58% (P= 0.002) and EFS was 23% versus 37% (P= 0.03). Patients who were in PD prior to the HDCY compared to their status after that had a significant improvement (P< 0.001), their OS was 38% to CR-PR group (38) versus 0% PD group (24). In general, mortality was 56 (53%), their cause was 23 (41.1%) PD, 7 (12.5%) related to HDCY, 12 (21.4%) related to AHSCT, 13 (23.2%) infections and 1 (1.8%) GVHD a RIC transplant. Besides that 1 (0.9%) patient developed MDS and is alive. B symptoms at diagnosis have appeared as a predictor factor for survival. Our study suggests HDS is an efficient treatment to improve status and to reduce tumor burden. Although it presented high toxicity related mortality, we consider the treatment feasible, especially considering the patients' poor prognosis.