Abstract
Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR], .74; 95% confidence interval [CI], .62 to .88; P < .001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P < .001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P = .001). In the high/very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR, .83; 95% CI, .68 to 1.00; P = .051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P = .002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/very-high risk DRI group.
| Original language | English (US) |
|---|---|
| Journal | Biology of Blood and Marrow Transplantation |
| DOIs | |
| State | Accepted/In press - 2020 |
All Science Journal Classification (ASJC) codes
- Hematology
- Transplantation
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In: Biology of Blood and Marrow Transplantation, 2020.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index
T2 - A Center for International Blood and Marrow Transplant Research Study
AU - Bejanyan, Nelli
AU - Zhang, Meijie
AU - Bo-Subait, Khalid
AU - Brunstein, Claudio
AU - Wang, Hailin
AU - Warlick, Erica D.
AU - Giralt, Sergio
AU - Nishihori, Taiga
AU - Martino, Rodrigo
AU - Passweg, Jakob
AU - Dias, Ajoy
AU - Copelan, Edward
AU - Hale, Gregory
AU - Gale, Robert Peter
AU - Solh, Melhem
AU - Kharfan-Dabaja, Mohamed A.
AU - Diaz, Miguel Angel
AU - Ganguly, Siddhartha
AU - Gore, Steven
AU - Verdonck, Leo F.
AU - Hossain, Nasheed M.
AU - Kekre, Natasha
AU - Savani, Bipin
AU - Byrne, Michael
AU - Kanakry, Christopher
AU - Cairo, Mitchell S.
AU - Ciurea, Stefan
AU - Schouten, Harry C.
AU - Bredeson, Christopher
AU - Munker, Reinhold
AU - Lazarus, Hillard
AU - Cahn, Jean Yves
AU - van Der Poel, Marjolein
AU - Rizzieri, David
AU - Yared, Jean A.
AU - Freytes, Cesar
AU - Cerny, Jan
AU - Aljurf, Mahmoud
AU - Palmisiano, Neil D.
AU - Pawarode, Attaphol
AU - Bacher, Vera Ulrike
AU - Grunwald, Michael R.
AU - Nathan, Sunita
AU - Wirk, Baldeep
AU - Hildebrandt, Gerhard C.
AU - Seo, Sachiko
AU - Olsson, Richard F.
AU - George, Biju
AU - de Lima, Marcos
AU - Hourigan, Christopher S.
AU - Sandmaier, Brenda M.
AU - Litzow, Mark
AU - Kebriaei, Partow
AU - Saber, Wael
AU - Weisdorf, Daniel
N1 - Funding Information: Financial disclosure: The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement U24CA076518 with the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement U24HL138660 with the NHLBI and NCI; Grant U24CA233032 from the NCI; Grants OT3 HL147741, R21 HL140314, and U01 HL128568 from the NHLBI; Contract HHSH250201700006C with the Health Resources and Services Administration (HRSA); Grants N00014-18-1-2888 and N00014-17-1-2850 from the Office of Naval Research; subaward from prime Contract Award SC1MC31881-01-00 with the HRSA; subawards from Prime Grant awards R01 HL131731 and R01 HL126589 from the NHLBI; subawards from prime Grant Awards 5P01CA111412, 5R01 HL129472, R01 CA152108, 1R01 HL131731, 1U01 AI126612, and 1R01 CA231141 from the NIH; and commercial funds from Actinium Pharmaceuticals, Adaptive Biotechnologies, Allovir, Amgen, Anonymous donation to the Medical College of Wisconsin, Anthem, Astellas Pharma US, Atara Biotherapeutics, BARDA, Be the Match Foundation, bluebird bio, Boston Children's Hospital, Bristol Myers Squibb, Celgene, Children's Hospital of Los Angeles, Chimerix, City of Hope Medical Center, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Dana-Farber Cancer Institute, Enterprise Science and Computing, Fred Hutchinson Cancer Research Center; Gamida-Cell, Genzyme, Gilead Sciences, GlaxoSmithKline, HistoGenetics, Immucor, Incyte, Janssen Biotech, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Japan Hematopoietic Cell Transplantation Data Center, Jazz Pharmaceuticals, Karius, Karyopharm Therapeutics, Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Mayo Clinic and Foundation Rochester, Medac, Mediware, Memorial Sloan Kettering Cancer Center, Merck & Company, Mesoblast, MesoScale Diagnostics, Millennium, Miltenyi Biotec, Mundipharma EDO, National Marrow Donor Program, Novartis Oncology, Novartis Pharmaceuticals, Omeros, Oncoimmune, OptumHealth, Orca Biosystems, PCORI, Pfizer, Phamacyclics, PIRCHE, Regeneron Pharmaceuticals, REGiMMUNE, Sanofi Genzyme, Seattle Genetics, Shire; Sobi, Spectrum Pharmaceuticals, St Baldrick's Foundation, Swedish Orphan Biovitrum, Takeda Oncology, The Medical College of Wisconsin, University of Minnesota, University of Pittsburgh, University of Texas MD Anderson, University of Wisconsin-Madison; Viracor Eurofins, and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, HRSA, or any other agency of the US Government. Funding Information: Financial disclosyure: The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement U24CA076518 with the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement U24HL138660 with the NHLBI and NCI; Grant U24CA233032 from the NCI; Grants OT3 HL147741, R21 HL140314, and U01 HL128568 from the NHLBI; Contract HHSH250201700006C with the Health Resources and Services Administration (HRSA); Grants N00014-18-1-2888 and N00014-17-1-2850 from the Office of Naval Research; subaward from prime Contract Award SC1MC31881-01-00 with the HRSA; subawards from Prime Grant awards R01 HL131731 and R01 HL126589 from the NHLBI; subawards from prime Grant Awards 5P01CA111412, 5R01 HL129472, R01 CA152108, 1R01 HL131731, 1U01 AI126612, and 1R01 CA231141 from the NIH; and commercial funds from Actinium Pharmaceuticals, Adaptive Biotechnologies, Allovir, Amgen, Anonymous donation to the Medical College of Wisconsin, Anthem, Astellas Pharma US, Atara Biotherapeutics, BARDA, Be the Match Foundation, bluebird bio, Boston Children's Hospital, Bristol Myers Squibb, Celgene, Children's Hospital of Los Angeles, Chimerix, City of Hope Medical Center, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Dana-Farber Cancer Institute, Enterprise Science and Computing, Fred Hutchinson Cancer Research Center; Gamida-Cell, Genzyme, Gilead Sciences, GlaxoSmithKline, HistoGenetics, Immucor, Incyte, Janssen Biotech, Janssen Pharmaceuticals, Janssen Research & Development, Janssen Scientific Affairs, Japan Hematopoietic Cell Transplantation Data Center, Jazz Pharmaceuticals, Karius, Karyopharm Therapeutics, Kite Pharma, Kyowa Kirin, Magenta Therapeutics, Mayo Clinic and Foundation Rochester, Medac, Mediware, Memorial Sloan Kettering Cancer Center, Merck & Company, Mesoblast, MesoScale Diagnostics, Millennium, Miltenyi Biotec, Mundipharma EDO, National Marrow Donor Program, Novartis Oncology, Novartis Pharmaceuticals, Omeros, Oncoimmune, OptumHealth, Orca Biosystems, PCORI, Pfizer, Phamacyclics, PIRCHE, Regeneron Pharmaceuticals, REGiMMUNE, Sanofi Genzyme, Seattle Genetics, Shire; Sobi, Spectrum Pharmaceuticals, St Baldrick's Foundation, Swedish Orphan Biovitrum, Takeda Oncology, The Medical College of Wisconsin, University of Minnesota, University of Pittsburgh, University of Texas MD Anderson, University of Wisconsin-Madison; Viracor Eurofins, and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, HRSA, or any other agency of the US Government. Conflict of interest statement: There are no conflicts of interest to disclose. Financial disclosure: See Acknowledgments on page XXX. Publisher Copyright: © 2020 American Society for Transplantation and Cellular Therapy
PY - 2020
Y1 - 2020
N2 - Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR], .74; 95% confidence interval [CI], .62 to .88; P < .001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P < .001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P = .001). In the high/very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR, .83; 95% CI, .68 to 1.00; P = .051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P = .002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/very-high risk DRI group.
AB - Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR], .74; 95% confidence interval [CI], .62 to .88; P < .001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P < .001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P = .001). In the high/very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR, .83; 95% CI, .68 to 1.00; P = .051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P = .002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/very-high risk DRI group.
UR - http://www.scopus.com/inward/record.url?scp=85095870377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095870377&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2020.09.026
DO - 10.1016/j.bbmt.2020.09.026
M3 - Article
C2 - 33010430
AN - SCOPUS:85095870377
SN - 1083-8791
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
ER -