Total Marrow and Lymphoid Irradiation (TMLI) - A Paradigm Shift in Radiation-Based Conditioning for Hematopoietic Cell Transplantation

Abstract

Total Marrow and Lymphoid Irradiation (TMLI) represents a technologically sophisticated evolution of conventional Total Body Irradiation (TBI) in the context of hematopoietic cell transplantation (HCT) conditioning. By harnessing the precision of Intensity Modulated Radiation Therapy (IMRT) delivered via helical tomotherapy or Volumetric Modulated Arc Therapy (VMAT) TMLI selectively irradiates the skeletal bone marrow, major lymph node chains, and spleen while dramatically reducing dose to critical organs at risk. This organ-sparing capacity permits dose escalation beyond the ceiling of conventional TBI (12 Gy), safely achieving doses up to 20 Gy without proportional increases in non-hematopoietic toxicity. Clinical evidence from multiple prospective trials demonstrates that TMLI yields low non-relapse mortality (NRM) rates, favorable overall survival (OS) and progression-free survival (PFS) across a spectrum of disease states including relapsed/refractory acute leukemia, complete remission transplants, haploidentical settings, and elderly patients unsuitable for conventional myeloablative regimens. This review comprehensively examines the radiobiological rationale, technical implementation, target delineation, clinical outcomes, and future directions of TMLI, with the aim of encouraging wider adoption of this transformative technique across Indian transplant centers.