High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma.

Summary:The aim of this study was to compare toxicity and efficacy of total body irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) vs busulfan, melphalan and thiotepa (Bu/Mel/T) in patients receiving autologous stem cell infusion (ASCI) for malignant lymphoma (NHL). Between September 1990 and July 1998, 351 patients with NHL were treated with TBI/CY/E (n = 221) or Bu/Mel/T (n = 130) followed by ASCI. Patients in first, or second remission, first responding or untreated relapse were defined as having less advanced disease before transplantation. The median follow-up was 5 years (range 1-9) and 3.5 years (1-6) for patients receiving TBI/CY/E and Bu/Mel/T, respectively. The cumulative probabilities of survival, event-free survival (EFS) and relapse at 5 years were 44%, 32%, 49% following TBI/CY/E and 42%, 34% and 42% following Bu/Mel/T. The probability of EFS at 5 years for patients who had prior dose-limiting radiation (n = 59) was 32% after Bu/Mel/T therapy. Transplant-related mortality was 16% for TBI/CY/E and 21% for Bu/Mel/T. In univariate and multivariate analyses, more advanced disease status was associated with poor outcome ( but almost all of these patients relapse and die, despite salvage treatment. Thirty to 60% of patients with aggressive NHL can be cured with intensive chemotherapy. However, the 2-year survival for patients who fail or relapse after induction chemotherapy is only 5 to 10%. 1 High-dose chemotherapy (HDC) supported with autologous stem cell infusion (ASCI) has proven efficacy in patients with first or subsequent chemotherapy-sensitive relapse, as well as in those patients who fail induction chemotherapy. 2 Radiation-based and chemotherapy-only preparative regimens have been evaluated in patients with NHL. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] However, the superiority of a specific HDC conditioning regimen for NHL has not been proven and few comparisons between regimens have been reported. [12][13][14][15] The Fred Hutchinson Cancer Research Center (FHCRC) has evaluated both radiation-based and chemotherapy-only conditioning regimens for the treatment of lymphomas. Phase II studies of both approaches have previously been published. 3,8,[16][17][18] High-dose fractionated total body irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) followed by ASCI was evaluated in patients with NHL (n = 43) and Hodgkin's disease (n = 10) who had failed to achieve a complete response after conventional chemotherapy or who had chemosensitive relapse. The 2-year Kaplan-Meier (KM) probabilities of survival, event-free survival (EFS) and relapse were 54%, 45% and 43%, respectively. The treatment-related mortality (TRM) was 17%. 16 Twenty-three patients with NHL and 17 with Hodgkin's disease were treated with the high-dose regimen of Busulfan (Bu), Melphalan (Mel) and Thiotepa (T) (Bu/Mel/T). The 2-year KM estimates of survival, EFS and relapse were 60%, 46% and 31%, respectively with a transplant-related mortality of 17%. 18 Randomized trials comparing the eff...

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See 1 more Smart Citation

Autologous stem cell transplantation for non-Hodgkin's lymphoma: comparison of radiation-based and chemotherapy-only preparative regimens

Gutiérrez-Delgado

Maloney

Press

et al. 2001

“…26,31 Etoposide was added in the hope of improving effectiveness without increasing the mortality rate substantially. The addition of etoposide to TBI/Cy 32,33 and to BCNU/Cy 13 improves effectiveness in the treatment of NHL. We present here the results of a large biinstitutional study of Bu/etoposide/Cy in the treatment of patients with NHL.…”

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Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma

Copelan

Penza

Pohlman

et al. 2000

Summary:The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eightytwo patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progressionfree survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248. Keywords: autotransplantation; non-Hodgkin's lymphoma; busulfan High-dose chemotherapy followed by autologous transplantation of hematopoietic progenitor cells is curative in many patients with NHL who fail primary therapy. [1][2][3][4] The superiority of this approach over standard chemotherapy has been proven in patients with chemotherapy-sensitive, relapsed intermediate and high-grade NHL. 5 Autotransplantation is also commonly performed in patients with more advanced

“…The majority of reported studies have explored the addition of etoposide to the standard regimen of totalbody irradiation (TBI) and cyclophosphamide. [31][32][33][34][35] The pilot trials of Gulati et al, 31 Horning et al, 33 and Weaver et al 34 appear to show a reduction in relapses when compared retrospectively with historical controls. However, these studies were hampered by heterogeneity of the study population and short follow-up.…”

Section: Discussionmentioning

confidence: 99%

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

Martı́n

Caballero

Pérez‐Simón

et al. 2004

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 ...