Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies [published erratum appears in Blood 1987 Jun;69(6):1789]

Abstract

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16–213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

Allogeneic and autologous bone marrow transplantation for acute leukemia and malignant lymphoma: Current status

“…Pre-and post-transplant treatment regimens have to be improved to decrease the relapse rate. Phase I and I1 studies addressing this issue have been reported (Santos et al, 1983;Messner et al, 1985;Blume et al, 1987). In the allogeneic situation, acute and chronic GVHD needs to be prevented without increasing the probability of relapse Storb et al, 1986;.…”

Discrete Pigmentation After Chemotherapy

“…The macular and papular lesions appeared five to nine days after initiation of therapy, were located predominantly on the trunk and upper extremities, and resolved spontaneously (14). Neither hyperpigmentation nor a predilection for occluded areas was noted, ln one study patients treated with total-body irradiation and high-dose etoposide prior to bone marrow transplantation developed a rash involving the palms, soles, and periorbital areas (18). However, it is unclear whether the cutaneous changes resulted from etoposide or from a graft-versus-host reaction.…”

Pharmacokinetics of high-dose etoposide

“…When administered before BMT in this study, the maximum tolerated dose of etoposide was 60 mg/kg (1.94 to 2.74 gm / m2). 1 The maximum tolerated dose of etoposide on a weekly intravenous schedule without BMT ranges from 0.172 to 0.3 gm/ m2 in various studies.' Because of its dependency on dose, the AUC at the maximum tolerated dose is likewise nearly an order of magnitude higher in the setting of subsequent BMT.…”