High dose cyclophosphamide, BCNU, and VP-16 (CBV) as a conditioning regimen for allogeneic bone marrow transplantation for patients with acute leukemia

Summary:To reduce relapse following allogeneic transplantation for AML, intensification of high-dose busulfan/cyclophosphamide using additional agents has been investigated but with few reported comparisons. We compared an intensified regimen of etoposide (60 mg/kg), busulphan (14 mg/kg), and cyclophosphamide (120 mg/kg) (BuCyVP) with BuCy2 in 237 AML patients. No significant difference in overall outcome was observed following BuCyVP (n ¼ 127) or BuCy2 (n ¼ 110). The 5-year survival was 27.3 and 30.1% following BuCyVP and BuCy2, respectively (P ¼ 0.48). Similarly, the 5-year cumulative incidence of relapse (CIR) was 28.3 and 34.8% with BuCyVP and BuCy2 (P ¼ 0.45), respectively. On multivariable analysis, patients transplanted in CR1 (P ¼ 0.002) and from related donors (P ¼ 0.013) had longer survival, while disease status at transplant was the only factor predicting CIR (P ¼ 0.002). In a separate analysis of CR1 patients (n ¼ 56), there was no significant difference in survival (P ¼ 0.37) or CIR (P ¼ 0.87) between the two regimens. However, for more advanced disease, there was a trend towards less relapse with BuCyVP (P ¼ 0.08), which was balanced by a higher cumulative incidence of transplant-related deaths (P ¼ 0.03) compared to BuCy2, resulting in similar survival. Overall, our results do not support the use of the more intensive BuCyVP regimen over BuCy2 in either early or more advanced disease AML patients. etoposide High-dose chemotherapy followed by allogeneic transplantation of hematopoietic stem cells is an important curative modality for many patients with acute myeloid leukemia (AML). The optimum intensity of the preparative regimen in this setting, however, remains uncertain. Almost two decades ago, the combination of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) without total body irradiation (TBI) was shown to permit successful hematopoietic engraftment and control of disease in many patients with leukemia.1,2 Subsequently, modification of the regimen by lowering the dose of cyclophosphamide to 120 mg/kg (BuCy2) appeared to be less toxic without loss of efficacy. 3,4 In three of five randomized trials comparing BuCy2 with TBI-based regimens in patients with chronic phase chronic myeloid leukemia (CML) and advanced acute leukemia, the BuCy2 regimen was associated with equivalent survival. [5][6][7] In spite of the potential for a graftversus-tumor effect, however, disease recurrence remains a significant cause of treatment failure following high-dose busulfan/cyclophosphamide and allogeneic stem cell transplantation, particularly in more advanced or refractory AML where over half of the patients relapse. 3,8 In an attempt to reduce relapse and improve overall outcome, several groups have intensified the busulfan/cyclophosphamide regimen by combining it with either TBI [9][10][11] or other chemotherapy agents, including high-dose thiotepa, 12,13 cytarabine, 14,15 melphalan, 16 or etoposide. 17-20The relative efficacy of these intensified regimens compared to busulfan/cyclophosphamide...

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confidence: 99%

High-dose busulfan, cyclophosphamide, and etoposide does not improve outcome of allogeneic stem cell transplantation compared to BuCy2 in patients with acute myeloid leukemia

Farag

Bolwell

Elder

et al. 2005

“…13,14 In the past, various cytotoxic agents have been used as preparation for allogeneic transplantation to reduce the incidence of relapse. They have included combinations such as cyclophosphamide, TBI; busulfan, cyclophosphamide; 8 high-dose ara-C and TBI; 15 high-dose etoposide and TBI; 16 high-dose cyclophosphamide, BCNU and VP-16 (CBV); 17 and etoposide, cyclophosphamide and TBI. 18 Leukemic relapse still remains an important cause of treatment failure in transplanted patients.…”

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confidence: 99%

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia

Jillella

Doria

Khan

et al. 1999

Summary:This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m 2 twice a day × six doses on days −7, −6, and −5; cyclophosphamide 1800 mg/m 2 on days −4 and −3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days −4, −3, −2, and −1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the KaplanMeier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.

“…14 Effective engraftment has been reported after CBV/allogeneic SCT for Hodgkin's lymphoma; these patients may be more immunosuppressed and less likely to exhibit host-versus-graft resistance than patients with NHL. 15 Additionally, Zander et al 16 confirmed the presence of donor hematopoiesis in all but one of 29 leukemia patients treated with CBV.…”

Section: Discussionmentioning

confidence: 93%

“…9,39,41 An early study of CBV for allotransplantation reported no significant organ toxicity among 29 acute leukemia patients. 16 In the recently reported LNH87-2 protocol for poor-risk aggressive NHL, there were no toxic deaths and no cases of late myelodysplasia among 125 autologous SCT patients receiving CBV with a BCNU dose of 300 mg/m. 2,42 Treatment-related toxicity was relatively low among our study patients.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13] In comparison, the experience with CBV for allogeneic transplants is described mostly in series of patients with a history of prior dose-limiting radiotherapy or included among patients treated with various conditioning regimens. [14][15][16] Our report is unique in its combination of patients mostly without prior radiation, the exclusion of Hodgkin disease patients, and the carmustine dosing of 450 mg/m 2 rather than the more toxic 600 mg/m 2 .…”

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confidence: 97%

See 1 more Smart Citation

High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin's lymphoma

Rossi

Becker

Emmons

et al. 2003

Summary:Allogeneic stem cell transplantation (SCT) has been shown to be a curative therapy for some patients with non-Hodgkin's lymphoma (NHL). Total-body irradiation and high-dose cyclophosphamide combinations are the most established conditioning regimens used in this setting. We examined the efficacy and toxicity of cyclophosphamide, BCNU, and VP-16 (CBV) as a suitable chemotherapy-only regimen for NHL patients. In total, 18 patients, median age 42 years, with NHL were treated with CBV followed by allotransplant. Patients had received a median of two prior chemotherapy regimens. Median times to neutrophil and platelet recovery were 19 and 15 days, respectively. Interstitial pneumonitis occurred in one patient. There have been four relapses after a median follow-up of 39 months. Overall, there were four deaths, one because of relapse. The 2-year estimates of relapse-free and overall survival are 56 and 76%, respectively. CBV is a safe and an effective alternative to TBI-containing regimens before allogeneic SCT for NHL.