Could (should) we abandon total body irradiation for conditioning in children with leukemia

Total body irradiation (TBI) is used since the introduction of hematopoietic cell transplantation (HCT) decades ago to eradicate patients normal and malignant hematopoiesis prior to its replacement with stem cells from an HLA-matched or mismatched donor. Over the many years of its use, long-term side effects became obvious especially in younger pediatric patients who received an allogeneic transplantation for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). These long-term known side effects of TBI including the occurrence of second malignancies can significantly impair the quality of life of the patients either still during childhood and/or when they reach adulthood. Although the benefit of a TBI-based conditioning regimen has been shown recently in a large randomized study, concerns remain whether TBI should be from now on the standard conditioning regimen for all children with ALL. The introduction of sensitive methods for detection of minimal residual disease (MRD) and new immunotherapies using bispecific antibodies or chimeric antibody receptor (CAR) T-cells in combination with non-TBI-based conditioning regimens have shown already promising results comparable with the outcome after TBI-based standard transplants or even better. In this review, various approaches are discussed which have been and should further be investigated in prospective trials with the aim to avoid TBI and its long-term side effects in pediatric patients with ALL.