KEY POINTS
- This narrative review searched PubMed/MEDLINE and Embase through April 2026 and examines TBI across myeloablative, reduced-intensity and nonmyeloablative allogeneic transplant platforms. The authors frame contemporary dosing broadly as ≥12 Gy for myeloablative, ≤2 Gy for nonmyeloablative, with approximately 4–8 Gy commonly occupying reduced/intermediate-intensity strategies.
- Historical dose escalation illustrates the efficacy–toxicity trade-off. Comparisons of 15.75 Gy versus 12 Gy showed less relapse at the higher dose but greater non-relapse mortality without an overall-survival advantage, contributing to the shift away from very intensive TBI schedules.
- A large 2019 analysis of 2,721 adults with AML, ALL, CLL or MDS receiving cyclophosphamide/TBI conditioning likewise associated doses above 12 Gy with lower relapse but worse non-relapse mortality and no survival benefit.
- Dose reduction may be reasonable within specific platforms rather than universally. An EBMT registry analysis of 639 adults with ALL in first remission found no significant differences in engraftment, relapse, non-relapse mortality, overall survival or GVHD-free relapse-free survival between 8-Gy and 12-Gy TBI combined with fludarabine; disease subtype and in-vivo T-cell depletion were more influential.
- At the low-intensity end, 2-Gy TBI permits transplantation in older or medically less fit patients with comparatively low treatment-related toxicity, but relapse remains a major limitation for high-risk disease. Intermediate 4–8 Gy schedules attempt to increase antileukemic effect without restoring the toxicity of full myeloablation.
- Importantly, more radiation is not consistently better even within reduced-intensity platforms. In a retrospective 413-patient lymphoma comparison summarized by the review, increasing TBI from 2 to 4 Gy was associated with 5-year non-relapse mortality of 47% versus 28% and overall survival of 31% versus 51%, without a significant reduction in relapse.
- Modern conformal strategies including total marrow irradiation and total marrow/lymphoid irradiation may separate marrow/lymphoid dose escalation from whole-body organ exposure. Early studies have delivered TMLI up to 20 Gy with encouraging outcomes in high-risk leukemia, but comparisons with conventional TBI remain predominantly nonrandomized and susceptible to selection bias.
CLINICAL TAKEAWAY
TBI dose should be interpreted as one component of a conditioning platform, not as an isolated determinant of transplant efficacy. Current evidence supports disease- and patient-adapted dosing, but heterogeneous regimens and limited randomized comparisons prevent a single universal “optimal” TBI schedule.