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Comparison of high doses of total body irradiation in myeloablative conditioning prior to hematopoietic cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Sabloff, M., Chhabra, S., Wang, T., Fretham, C., Kekre, N., Abraham, A., Adekola, K., Auletta, J. J., Barker, C., Beitinjaneh, A. M., Bredeson, C., Cahn, J., Diaz, M. A., Freytes, C., Gale, R. P., Ganguly, S., Gergis, U., Guinan, E., Hamilton, B., Hashmi, S., Hematti, P., Hildebrandt, G., Holmberg, L., Hong, S., Lazarus, H. M., Martino, R., Muffly, L., Nishihori, T., Perales, M., Yared, J., Mineishi, S., Stadtmauer, E. A., Pasquini, M. C., Loren, A. W. 2019

Abstract

Malignancy relapse is the most common cause of treatment failure among recipients of hematopoietic cell transplantation (HCT). Conditioning dose intensity can reduce disease relapse, but it is offset by toxicities. Improvements in radiotherapy techniques and supportive care may translate to better outcomes with higher irradiation doses in the modern era. This study compares outcomes of recipients of increasing doses of high dose total body irradiation (TBI) divided into intermediate high dose (IH 13-13.75 Gy) and high dose (HD 14 Gy) to standard dose (SD 12Gy) with cyclophosphamide (Cy). A total of 2,721 patients ages of 18 to 60 with hematologic malignancies receiving HCT from 2001 to 2013 were included. Cumulative incidence of non-relapse mortality (NRM) at 5 years was 28% (95% Cumulative Incidence [CI] 25-30%), 32% (95%CI 29-36%) and 34% (95%CI 28-39%) for SD, IH and HD, respectively (p=0.02). Patients receiving IH-TBI had a 25% higher risk of NRM compared to SD-TBI (12 Gy) (p=0.007). Corresponding cumulative incidence of relapse was 36% (95%CI 34-38%), 32% (95%CI 29-36%) and 26% (95%CI 21-31%) (p=0.001). Hazard ratio for mortality compared to SD were 1.06 (95% 0.94-1.19, p=0.36) for IH and 0.89 (95% CI 0.76-1.05, p=0.17) for HD. The study demonstrates that despite improvements in supportive care, myeloablative conditioning using higher doses of TBI (with Cy) leads to worse non-relapse mortality and offers no survival benefit over SD, despite reducing disease relapse.

View details for DOI 10.1016/j.bbmt.2019.08.012

View details for PubMedID 31473319