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Observational Study
. 2019 Dec;25(12):2398-2407.
doi: 10.1016/j.bbmt.2019.08.012. Epub 2019 Aug 29.

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

Mitchell Sabloff  1 , Saurabh Chhabra  2 , Tao Wang  3 , Caitrin Fretham  4 , Natasha Kekre  5 , Allistair Abraham  6 , Kehinde Adekola  7 , Jeffery J Auletta  8 , Christopher Barker  9 , Amer M Beitinjaneh  10 , Christopher Bredeson  5 , Jean-Yves Cahn  11 , Miguel Angel Diaz  12 , Cesar Freytes  13 , Robert Peter Gale  14 , Siddhartha Ganguly  15 , Usama Gergis  16 , Eva Guinan  17 , Betty K Hamilton  18 , Shahrukh Hashmi  19 , Peiman Hematti  20 , Gerhard Hildebrandt  21 , Leona Holmberg  22 , Sanghee Hong  23 , Hillard M Lazarus  24 , Rodrigo Martino  25 , Lori Muffly  26 , Taiga Nishihori  27 , Miguel-Angel Perales  28 , Jean Yared  29 , Shin Mineishi  30 , Edward A Stadtmauer  31 , Marcelo C Pasquini  32 , Alison W Loren  33
Affiliations
Observational Study

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

Mitchell Sabloff et al. Biol Blood Marrow Transplant. 2019 Dec.

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.

Keywords: Allogeneic hematopoietic cell transplantation; Hematologic malignancies; Myeloablative conditioning; Total body irradiation.

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Figures

Figure 1.
Figure 1.
Cumulative incidence function of non-relapse mortality by dose of TBI
Figure 2.
Figure 2.
Cumulative incidence function of relapse by dose of TBI
Figure 3.
Figure 3.
Disease-free survival by dose of TBI
Figure 4.
Figure 4.
Kaplan-meier curve of overall survival by dose of TBI
See this image and copyright information in PMC

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