Comparison of High Doses of Total Body Irradiation in Myeloablative Conditioning before Hematopoietic Cell Transplantation
Por:
Sabloff, M, Chhabra, S, Wang, T, Fretham, C, Kekre, N, Abraham, A, Adekola, K, Auletta, JJ, Barker, C, Beitinjaneh, AM, Bredeson, C, Cahn, JY, Diaz, MA, Freytes, C, Gale, RP, Ganguly, S, Gergis, U, Guinan, E, Hamilton, BK, Hashmi, S, Hematti, P, Hildebrandt, G, Holmberg, L, Hong, S, Lazarus, HM, Martino, R, Muffly, L, Nishihori, T, Perales, MA, Yared, J, Mineishi, S, Stadtmauer, EA, Pasquini, MC, Loren, AW
Publicada:
1 dic 2019
Resumen:
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% Cl, 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. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Filiaciones:
Sabloff, M:
Univ Ottawa, Dept Med, Div Hematol, Ottawa, ON, Canada
Ottawa Hosp, Res Inst, Ottawa, ON, Canada
Chhabra, S:
Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA
Med Coll Wisconsin, Dept Med, Div Hematol Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA
Wang, T:
Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA
Med Coll Wisconsin, Inst Hlth & Equ, Div Biostat, Milwaukee, WI 53226 USA
Fretham, C:
Natl Marrow Donor Program Be Match, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA
Kekre, N:
Ottawa Hosp, Res Inst, Ottawa, ON, Canada
Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada
Abraham, A:
Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA
Adekola, K:
Northwestern Univ, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA
Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
Auletta, JJ:
Nationwide Childrens Hosp, Blood & Marrow Transplant Program, Columbus, OH USA
Nationwide Childrens Hosp, Host Def Program, Columbus, OH USA
Nationwide Childrens Hosp, Div Hematol, Columbus, OH USA
Nationwide Childrens Hosp, Div Oncol, Columbus, OH USA
Nationwide Childrens Hosp, Div Bone Marrow Transplant & Infect Dis, Columbus, OH USA
Barker, C:
Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA
Beitinjaneh, AM:
Univ Miami, Div Hematol Oncol, Miami, FL USA
Bredeson, C:
Ottawa Hosp, Res Inst, Ottawa, ON, Canada
Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada
Cahn, JY:
CHU Grenoble Alpes, Dept Hematol, Grenoble, France
Diaz, MA:
Hosp Infantil Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain
Freytes, C:
Texas Transplant Inst, Adult Blood & Marrow Transplant Program, San Antonio, TX USA
Gale, RP:
Imperial Coll London, Dept Med, Div Expt Med, Hematol Res Ctr, London, England
Ganguly, S:
Univ Kansas Hlth Syst, Div Hematol Malignancy & Cellular Therapeut, Kansas City, KS USA
Gergis, U:
New York Presbyterian Hosp, Hematolg Malignancies & Bone Marrow Transplant, Dept Med Oncol, Weill Cornell Med Ctr, New York, NY USA
Guinan, E:
Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
Hamilton, BK:
Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA
Hashmi, S:
Mayo Clin, Dept Internal Med, Rochester, MN USA
King Faisal Specialist Hosp & Res Ctr, Ctr Oncol, Riyadh, Saudi Arabia
Hematti, P:
Univ Wisconsin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI USA
Hildebrandt, G:
Univ Kentucky, Markey Canc Ctr, Lexington, KY USA
Holmberg, L:
Fred Hutchinson Canc Res Ctr, Div Med Oncol, 1124 Columbia St, Seattle, WA 98104 USA
Hong, S:
Cleveland Clin, Taussig Canc Ctr, Dept Med, Cleveland, OH 44106 USA
Lazarus, HM:
Case Western Reserve Univ, Cleveland, OH 44106 USA
Martino, R:
Hosp Santa Creu & Sant Pau, Div Clin Hematol, Barcelona, Spain
Muffly, L:
Stanford Univ, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA
Nishihori, T:
H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA
Perales, MA:
Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA
Yared, J:
Univ Maryland, Dept Med, Blood & Marrow Transplantat Program, Div Hematol Oncol,Greenebaum Comprehens Canc Ctr, Baltimore, MD 21201 USA
Mineishi, S:
Penn State Hershey Med Ctr, Dept Med, Div Hematol & Oncol, Hershey, PA USA
Stadtmauer, EA:
Univ Penn, Med Ctr, Div Hematol Oncol, Abramson Canc Ctr,Dept Med, Philadelphia, PA 19104 USA
Pasquini, MC:
Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA
Loren, AW:
Univ Penn, Dept Med, Perelman Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA
Green Accepted, Hybrid Gold
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