Bone Marrow Transplantation

Abstract

Substantial chemotherapy data in humans with cancer and leukemia indicate a dose-response relationship: higher doses produce more cure (Fig. 1). Many chemotherapeutic agents, especially alkylating agents, exhibit a steep dose-response curve (Frei and Canellos 1980). However, the dose-limiting toxicity is myelosuppression. Bone marrow transplantation offers one way to circumvent treatment resistance by allowing significant dose escalation. The underlying strategy is to give very high, even myeloablative doses of chemotherapy or radiation, or both, followed by rescue with bone marrow derived hematopoietic stem cells. It is postulated that these higher doses of drugs and radiation eradicate a greater proportion of cancer cells than conventional doses and thereby result in a higher response rate and more cures. Most high-dose treatment regimens studied to date have utilized alkylating agents, etoposide and/or nitrosoureas with or without total body irradiation (TBI). (Thomas et al. 1975; Clift et al. 1987; Santos et al. 1983; Jagannath et al. 1986) A common regimen consists of cyclophosphamide (60 mg/kg on each of 2 days) followed by TBI (Thomas et al. 1975; Clift et al. 1987). Fractionated TBI has been used in attempts to reduce the toxicity of irradiation; doses per fraction range from 1.25 to 3.3 Gy, and total doses from 5.0 to 15.75 Gy.