Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan elimination is the formation of a tetrahydrothiophenium ion (THT+) in a glutathi...

PURPOSE Personalizing intravenous busulfan doses to a target plasma concentration at steady state (Css) is an essential component of hematopoietic cell transplantation (HCT). We sought to develop a population pharmacokinetic model to predict i.v. busulfan doses over a wide age spectrum (0.1-66 years) that accounts for differences in age and body size. EXPERIMENTAL DESIGN A population pharmaco...

1,7-Heptanediol disulfamate (hepsulfam, NSC 329680) is a new anti-cancer agent which is currently undergoing phase I clinical trials. The mechanism of action of this compound is not clear at this time. We have recently shown that hepsulfam was more toxic to L1210 leukemia cells than was busulfan. Consistent with the difference in toxicity, we found that hepsulfam induced DNA interstrand cross-l...

Several methods have been developed for suppression of endogenous spermatogenesis in recipient males before spermatogonial stem cells transfer. Currently the chemical treatment with alkylating agent busulfan is the method of choice in mammals. Still, in different mammalian species wide variability in optimal doses of busulfan has been demonstrated, whereas in birds, the dosage has not yet been ...

Ovarian dysfunction leading to hormonal imbalance plays a crucial role in uterine carcinogenesis in rats as well as women. However, the effects of a reduction in primordial follicles at birth on uterine adenocarcinoma development have hitherto not been determined. The present study was therefore conducted using female Donryu rats, a high incidence rat strain of uterine adenocarcinoma. The anima...

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. M...

Background: Busulfan is an alkylating agent, which inhibits cell dividing by sticking to one of the DNA strands. The aim of the present study was establishment and stereological evaluation of testes of azoospermic animal model using busulfan in albino hamster. Materials and Methods: Male adult albino hamsters were randomly assigned into 3 groups. The first group was injected one dose of busulfa...

Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae. Busulfan and cyclophosphamide have been used as an alternative to TBI. Etoposide also has been widely used to enhance antileukemic effect. However, toxicities have been reported in some studies using busulfan, cyclophosphamide, and etoposid...

Introduction: Chemotherapy has adverse effects on spermatogenesis and results in reversible or irreversible oligozoospermia or azoospermia. Little is known about the ultrastructural alterations of male germ cells following busulfan administration, as an anti-cancer drug. The present study aimed to study the ultrastructural alterations or apoptotic features of male mouse germ cells, following ad...

The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hem...