Results of autologous transplantation in lymphoma are not improved by increasing the dose of etoposide in the BEAM regimen: a single-centre sequential-cohort study

Abstract

Summary:We have undertaken a retrospective sequential-cohort analysis of 131 lymphoma patients treated with the BEAM regimen and autologous stem cell transplantation, to compare BEAM at standard doses (sBEAM; n ¼ 67 from May 1990 to April 1995) and BEAM with escalated etoposide dose from 800 to 1600 mg/m 2 (eBEAM; n ¼ 64 from May 1995 to June 1999). Transplant-related mortality and incidence of secondary malignancies were similar in both groups. Disease progression was significantly lower in indolent lymphoma (IL) patients receiving eBEAM (7 vs 43%), although survival was comparable due to a higher toxic mortality in the eBEAM group. The 5-year event-free survival and overall survival were better in Hodgkin's disease (HD) patients treated with eBEAM (70 and 77%, respectively) compared to sBEAM (58 and 69%, respectively), but the difference was not statistically significant. In aggressive lymphomas, no difference was detected between groups. Our results indicate that while escalation of the etoposide doses in the BEAM conditioning regimen does not appear to improve outcome, encouraging results in IL and HD may warrant further studies. High-dose chemotherapy supported by autologous stemcell transplantation (ASCT) is widely used for relapsing or resistant non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) patients, and may be a promising procedure for initial therapy of aggressive NHL with poor prognostic features. 1 Under 35% of HD and under 20% of aggressive NHL patients achieve long-term disease-free survival (DFS) with conventional chemotherapy. 2-4 ASCT results in DFS of 30-65% in primary refractory or relapsed HD 5-10 and 30-50% in aggressive NHL. [11][12][13][14][15][16] Randomized studies have demonstrated the superiority of ASCT to standard salvage chemotherapy for patients with resistant or relapsed HD, 2,3 relapsed aggressive lymphoma 4 or relapsed follicular lymphoma. 17 These results suggest a correlation between dose intensity and disease control. Thus, it is possible that further doseintensification of the conditioning regimen may improve outcome of patients undergoing ASCT. Escalation of the BCNU dose in BEAM and CBV regimens has resulted in increased mortality due to interstitial pneumonitis. 18,19 Escalation of the melphalan dose resulted in increased mucositis and haemorrhagic cystitis. 20 Mills et al 21 escalated the dose of etoposide in the BEAM protocol from 800 to 1600 mg/m 2 over 4 days, and then to 2400 mg/m 2 over 4 days. The maximum tolerable dose was 1600 mg/m 2 over 4 days, but no conclusions could be drawn regarding the impact of the escalated etoposide dose on tumour response and DFS. We have confirmed 22 that increasing the etoposide dose from 800 to 1600 mg/m 2 in BEAM regimen is not associated with greater early toxicity.We have now analysed the impact of the etoposide dose in 131 lymphoma patients in terms of early and late toxicities, response and survival. Patients and methods PatientsA total of 131 consecutive lymphoma patients treated at a single institution with the BEAM ...

Mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) followed by autologous stem cell transplantation for patients with chemosensitive aggressive non‐Hodgkin lymphoma

“…In a previous study using the BEAM regimen, the 3‐year OS of patients with aggressive NHL was 55–56% [15]. In another study, the 5‐year EFS and OS were 59 and 63%, respectively [16]. In this study, the median EFS was 17.9 months and the estimated 2‐year and 3‐year OS was both 64.2% (Fig.…”

Safety and efficacy of high-dose ranimustine, cytarabine, etoposide and CY (MCVAC) regimen followed by autologous peripheral blood stem cell transplantation for high-risk diffuse large B-cell lymphoma

“…The incidence of therapy-related MDS/AML (cumulative incidence of 3.3%) seemed identical to those of other studies. 20,23 In two patients, severe pulmonary impairment developed 61.4 and 69.2 months after transplant. Pulmonary toxicity has been well recognized as a complication related to the use of BCNU-containing regimens.…”

“…16,[19][20][21] Late-onset adverse events, however, included therapy-related MDS/AML and severe pulmonary toxicity. Therapy-related MDS/AML has been a wellrecognized complication after high-dose chemotherapy, mainly in the setting of autologous hematopoietic SCT for non-Hodgkin's lymphoma.…”

Novel Preparative Regimens in Hematopoietic Stem Cell Transplantation

“…Similarly, there are no prospective randomized comparisons of the commonly used regimens CBV, BEAM, BEAC and TBI-Cy-VP16. Therefore, the (mostly) phase II trials described below reflect to a large extent institutional experience and investigator choice, and should be analyzed within that context [66][67][68].…”