Single dose versus fractionated total body irradiation before bone marrow transplantation: radiobiological and clinical considerations.

Purpose: This present review is intended to evaluate the specific influence of fractionation of total body irradiation on the outcome of a subsequent bone marrow transplantation.
Methods and Materials: Available experimental and clinical data on the influence of fractionation on leukemia cell killing, immunosuppression, and sparing of normal tissues were analyzed.
Results: Review of available data shows: (a) The role of fractionation on leukemia cell killing may vary with the leukemia type. For acute nonlymphoblastic leukemia, a few experimental and several clinical studies show no or little fractionation effect; a 12-13 Gy fractionated scheme could, therefore, be more efficient than a conventional 10 Gy single dose total body irradiation. For chronic myelogenous leukemia, some sensitivity to fractionation is suggested, so that an increase in total or fractional dose may be necessary in fractionated schemes to equate the efficacy of a 10 Gy single dose. For acute lymphoblastic leukemia, a high fractionation sensitivity was observed for some leukemic cell lines in vitro, without undisputable clinical confirmation for the moment. (b) Numerous experimental studies have demonstrated that the immunosuppressive effect of total body irradiation, a major determinant of engraftment, is highly fractionation sensitive. In humans, high rates of graft failures have been reported when T-cell depletion of the graft was associated to fractionated total body irradiation schedules. (c) A large amount of radiobiological and clinical data have demonstrated that late radiation-induced injuries to normal tissues and organs are highly fractionation sensitive. However, in a context of total body irradiation for bone marrow transplantation, the number of other determinants of normal tissue damage makes it difficult to demonstrate a clear-cut advantage of fractionated over single dose scheme, with a possible exception for children.
Conclusions: In 1994, available data suggest that very cautious attempts could be made to adapt total body irradiation schedules to the potential normal tissue toxicity, T-cell depletion, and to the type of leukemia.