Comparison of High Doses of Total Body Irradiation in Myeloablative Conditioning before Hematopoietic Cell Transplantation

Mitchell Sabloff, Saurabh Chhabra, Tao Wang, Caitrin Fretham, Natasha Kekre, Allistair Abraham, Kehinde Adekola, Jeffery J. Auletta, Christopher Barker, Amer M. Beitinjaneh, Christopher Bredeson, Jean Yves Cahn, Miguel Angel Diaz, Cesar Freytes, Robert Peter Gale, Siddhartha Ganguly, Usama Gergis, Eva Guinan, Betty K. Hamilton, Shahrukh HashmiPeiman Hematti, Gerhard Hildebrandt, Leona Holmberg, Sanghee Hong, Hillard M. Lazarus, Rodrigo Martino, Lori Muffly, Taiga Nishihori, Miguel Angel Perales, Jean Yared, Shin Mineishi, Edward A. Stadtmauer, Marcelo C. Pasquini, Alison W. Loren

Research output: Contribution to journalArticle

1 Scopus citations

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 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) with standard dose (SD; 12 Gy) with cyclophosphamide. A total of 2721 patients ages 18 to 60 years with hematologic malignancies receiving HCT from 2001 to 2013 were included. Cumulative incidences of nonrelapse mortality (NRM) at 5 years were 28% (95% confidence interval [CI], 25% to 30%), 32% (95% CI, 29% to 36%), and 34% (95% CI, 28% to 39%) for SD, IH, and HD, respectively (P =.02). Patients receiving IH-TBI had a 25% higher risk of NRM compared with those receiving SD-TBI (12 Gy) (P =.007). Corresponding cumulative incidences of relapse were 36% (95% CI, 34% to 38%), 32% (95% CI, 29% to 36%), and 26% (95% CI, 21% to 31%; P =.001). Hazard ratios for mortality compared with SD were 1.06 (95% CI,.94 to 1.19; P =.36) for IH and.89 (95% CI,.76 to 1.05; P =.17) for HD. The study demonstrates that despite improvements in supportive care, myeloablative conditioning using higher doses of TBI (with cyclophosphamide) leads to worse NRM and offers no survival benefit over SD, despite reducing disease relapse.

Original languageEnglish (US)
Pages (from-to)2398-2407
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number12
DOIs
StatePublished - Dec 2019

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

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    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. Y., Diaz, M. A., Freytes, C., Gale, R. P., Ganguly, S., Gergis, U., Guinan, E., Hamilton, B. K., ... Loren, A. W. (2019). Comparison of High Doses of Total Body Irradiation in Myeloablative Conditioning before Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 25(12), 2398-2407. https://doi.org/10.1016/j.bbmt.2019.08.012