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Reduced Intensity Conditioning Regimens in Combination with Total Marrow and Lymphoid Irradiation

  • Joseph RosenthalEmail author
Chapter
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Abstract

Allogeneic hematopoietic stem cell transplantation (HCT) following myeloablative chemotherapy (MAC) has been established as a proven treatment modality in patients with hematological malignancies. Total body irradiation (TBI) as an element of MAC has been shown to have a potent antileukemic effect, but it is associated with a high rate of toxicity at the standard levels of 12–15 Gy delivered to all organs. However, its use is limited due to a high rate of life-threatening toxicities, evident particularly in older patients and in patients with preexisting morbidities. Reduced-intensity conditioning (RIC) regimens were developed in an attempt to expand the curative potential of HCT to patients who are not eligible for a fully MAC regimens. Fludarabine (FLU) and melphalan (MEL) are two of the most commonly agents used in RIC. Multiple reports have demonstrated that long-term survival and disease control can be obtained with HCT following RIC; however, patients with advanced disease at the time of transplantation have suffered significantly higher rates of relapsed leukemia. That led to an assumption that the reduction in treatment intensity associated with the use of RIC may have a negative impact on long-term leukemic control. A sound hypothesis is that technologies that may improve the antileukemic effect of treatment while maintaining a low rate of toxicities may improve outcome of RIC. Total marrow and lymphatic irradiation (TMLI) using intensity modulated radiation therapy (IMRT) enables the delivery of effective antileukemic doses to the marrow and lymphatic organ, and at the same time, delivering less lower doses to the adjacent organs, resulting in reduced toxic exposure to these organs. The chapter summarizes the experience of using helio-tomotherapy, an IMRT modality in combination with FLU/MEL, to augment the antileukemic effects of a standard RIC regimen without increasing the toxicity of the regimen.

Keywords

Myeloablative conditioning (MAC) Reduced intensity conditioning (RIC) Total body irradiation (TBI) Total marrow and lymphoid irradiation (TMLI) Fludarabine (FLU) Melphalan (MEL) 

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of PediatricsCity of HopeDuarteUSA

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