Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation

Abstract

Forty-three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty-eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day -8, cyclophosphamide 60 mg/kg/day intravenously on days -7 and -6, and total body irradiation at 170 cGy twice a day on days -3, -2, and -1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease.

Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide

“…Finally, TBI-VP-16-CY has been effective for autologous stem cell transplantation for pediatric ALL. 16 However, Brown et al, 6 Giralt et al 7 and Yau et al, 8 in non-randomized clinical studies of adults with acute leukemia undergoing allogeneic bone marrow transplantation, all observed relatively high rates of regimen-related toxicity and no apparent advantage of TBI-VP16-Cy over TBI-Cy or other regimens employed in allogeneic transplantation for acute leukemia. In contrast, the results of this study demonstrate that in children, TBI-VP16-Cy is a safe and effective regimen.…”

“…On the other hand, in all three aforementioned adult studies, toxicity and in particular, pulmonary toxicity, was a major problem. Giralt et al 7 and Yau et al 8 reported incidences of diffuse alveolar hemorrhage causing death of 8% and 7%, respectively. The lower toxicity rates observed in the present study and in the Horstmann et al 17 study are likely partly attributable to the younger age of the patients.…”

“…3 Alternatively, many investigators sought improved preparative regimen efficacy, by incorporating supplemental chemotherapy agents such as busulphan, 4 cytarabine, 5 or etoposide. [6][7][8] Previous clinical studies of one of these novel regimens, total body irradiation, etoposide and cyclophosphamide combined with allogeneic bone marrow transplantation for adults with acute leukemia have yielded mixed results. [6][7][8] To assess the safety and efficacy of this combination in pediatric patients, we evaluated the outcomes of 41 children and adolescents who received allogeneic bone marrow transplants for acute leukemia after total body irradiation, etoposide and cyclophosphamide.…”

Allogeneic bone marrow transplantation for acute myeloblastic leukaemia in remission: risk factors for long-term morbidity and mortality

“…Similarly, previous reports noted high rates of regimen-related toxicity in adult patients with advanced disease who received intensified conditioning. 49,50 A randomised trial comparing the effectiveness of 12 with 15.75 Gy in patients with AML in CR1 concluded that the higher TBI dose resulted in a decreased relapse rate but in an increase in TRM, and therefore, had no positive impact on EFS. 51 Major ABO incompatibility appeared as a risk factor for chronic GvHD and TRM on multivariate analysis.…”

A myeloablative conditioning regimen for patients with impaired cardiac function undergoing allogeneic stem cell transplantation: Reduced cyclophosphamide combined with etoposide and total body irradiation

“…Although combination of TBI with VP-16 and CY as conditioning regimens has been reported to be effective for patients with hematological malignancies undergoing allogeneic HSCT [14][15][16][17][18], the dose of VP-16, CY, and TBI has been widely varied and no report clearly described the cardiotoxicity of these regimens. On the other hand, some reports on VP-16 (60 mg/kg) and TBI (12 Gy) (VP/TBI) suggested that VP/TBI might increase the risk of graft rejection.…”