TY - JOUR
T1 - Comparison of High Doses of Total Body Irradiation in Myeloablative Conditioning before Hematopoietic Cell Transplantation
AU - Sabloff, Mitchell
AU - Chhabra, Saurabh
AU - Wang, Tao
AU - Fretham, Caitrin
AU - Kekre, Natasha
AU - Abraham, Allistair
AU - Adekola, Kehinde
AU - Auletta, Jeffery J.
AU - Barker, Christopher
AU - Beitinjaneh, Amer M.
AU - Bredeson, Christopher
AU - Cahn, Jean Yves
AU - Diaz, Miguel Angel
AU - Freytes, Cesar
AU - Gale, Robert Peter
AU - Ganguly, Siddhartha
AU - Gergis, Usama
AU - Guinan, Eva
AU - Hamilton, Betty K.
AU - Hashmi, Shahrukh
AU - Hematti, Peiman
AU - Hildebrandt, Gerhard
AU - Holmberg, Leona
AU - Hong, Sanghee
AU - Lazarus, Hillard M.
AU - Martino, Rodrigo
AU - Muffly, Lori
AU - Nishihori, Taiga
AU - Perales, Miguel Angel
AU - Yared, Jean
AU - Mineishi, Shin
AU - Stadtmauer, Edward A.
AU - Pasquini, Marcelo C.
AU - Loren, Alison W.
N1 - Funding Information:
The authors thank Jennifer Motl for editorial support in accordance with Good Publication Practice guidelines ( http://www.ismpp.org/gpp3). Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement (1U24HL138660) from the NHLBI and NCI; a contract (HHSH250201700006C) with Health Resources and Services Administration; grants N00014‐17‐1‐2388, N00014‐17‐1‐2850, and N00014‐18‐1‐2045 from the Office of Naval Research (HHSH250201700006C); and grants from Adaptive Biotechnologies; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. Asterisk indicates corporate members. Conflict of interest statement: There are no conflicts of interest to report.
Funding Information:
Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; a grant/cooperative agreement (1U24HL138660) from the NHLBI and NCI; a contract (HHSH250201700006C) with Health Resources and Services Administration; grants N00014‐17‐1‐2388, N00014‐17‐1‐2850, and N00014‐18‐1‐2045 from the Office of Naval Research (HHSH250201700006C); and grants from Adaptive Biotechnologies; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government.
Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Allogeneic hematopoietic cell transplantation
KW - Hematologic malignancies
KW - Myeloablative conditioning
KW - Total body irradiation
UR - http://www.scopus.com/inward/record.url?scp=85072691397&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072691397&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.08.012
DO - 10.1016/j.bbmt.2019.08.012
M3 - Article
C2 - 31473319
AN - SCOPUS:85072691397
VL - 25
SP - 2398
EP - 2407
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 12
ER -