TY - JOUR
T1 - Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1
AU - Ustun, Celalettin
AU - Kim, Soyoung
AU - Chen, Min
AU - Beitinjaneh, Amer M.
AU - Brown, Valerie I.
AU - Dahi, Parastoo B.
AU - Daly, Andrew
AU - Diaz, Miguel Angel
AU - Freytes, Cesar O.
AU - Ganguly, Siddhartha
AU - Hashmi, Shahrukh
AU - Hildebrandt, Gerhard C.
AU - Lazarus, Hillard M.
AU - Nishihori, Taiga
AU - Olsson, Richard F.
AU - Page, Kristin M.
AU - Papanicolaou, Genovefa
AU - Saad, Ayman
AU - Seo, Sachiko
AU - William, Basem M.
AU - Wingard, John R.
AU - Wirk, Baldeep
AU - Yared, Jean A.
AU - Perales, Miguel Angel
AU - Auletta, Jeffery J.
AU - Komanduri, Krishna V.
AU - Lindemans, Caroline A.
AU - Riches, Marcie L.
N1 - Funding Information:
The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; Grant/Cooperative Agreement 4U10HL069294 from the National Institues of Health, National Heart, Lung, and Blood Institute and National Cancer Institute; contract HHSH250201200016C with the Health Resources and Services Administration (Department of Health and Human Services); and 2 grants (N00014-17-1-2388 and N0014-17-1-2850) from the Office of Naval Research. The CIBMTR is also supported by grants from Actinium Pharmaceuticals, Inc., Amgen, Inc., Amneal Biosciences, Angiocrine Bioscience, Inc., an 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, Cerus Corporation, Chimerix, Inc., Fred Hutchinson Cancer Research Center, Gamida Cell Ltd., Gilead Sciences, Inc., HistoGenetics, Inc., Immucor, Incyte Corporation, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Inc., Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Inc., medac GmbH, MedImmune, The Medical College of Wisconsin, Mediware, Merck & Co., Inc., Mesoblast, MesoScale Diagnostics, Inc., Millennium, the Takeda Oncology Co., Miltenyi Biotec, National Marrow Donor Program, Neovii Biotech NA, Inc., Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Co, Ltd.-Japan, PCORI, Pfizer Inc., Pharmacyclics, LLC, PIRCHE AG, Sanofi Genzyme, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Inc., St. Baldrick's Foundation, Sunesis Pharmaceuticals, Inc., Swedish Orphan Biovitrum, Inc., Takeda Oncology, Telomere Diagnostics, Inc., and the 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, the Health Resources and Services Administration, or any other agency of the US Government.
Funding Information:
Acknowledgments The CIBMTR is supported primarily by Public Health Service Grant/ Cooperative Agreement 5U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; Grant/Cooperative Agreement 4U10HL069294 from the National Institues of Health, National Heart, Lung, and Blood Institute and National Cancer Institute; contract HHSH250201200016C with the Health Resources and Services Administration (Department of Health and Human Services); and 2 grants (N00014-17-1-2388 and N0014-17-1-2850) from the Office of Naval Research. The CIBMTR is also supported by grants from Actinium Pharmaceuticals, Inc., Amgen, Inc., Amneal Biosciences, Angiocrine Bioscience, Inc., an 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, Cerus Corporation, Chimerix, Inc., Fred Hutchinson Cancer Research Center, Gamida Cell Ltd., Gilead Sciences, Inc., HistoGenetics, Inc., Immucor, Incyte Corporation, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Inc., Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Inc., medac GmbH, MedImmune, The Medical College of Wisconsin, Mediware, Merck & Co., Inc., Mesoblast, MesoScale Diagnostics, Inc., Millennium, the Takeda Oncology Co., Miltenyi Biotec, National Marrow Donor Program, Neovii Biotech NA, Inc., Novartis Pharmaceuticals Corporation, Otsuka Pharmaceutical Co, Ltd.–Japan, PCORI, Pfizer Inc., Pharmacyclics, LLC, PIRCHE
Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019/9/10
Y1 - 2019/9/10
N2 - Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT-comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, <1-99 days]; RIC/NMA, 21 days [range, <1-100 days]; P < .001). Patients receivingMAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95%CI, 36-42]; P5.046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P < .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCTwas greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P < .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.
AB - Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT-comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, <1-99 days]; RIC/NMA, 21 days [range, <1-100 days]; P < .001). Patients receivingMAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95%CI, 36-42]; P5.046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P < .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCTwas greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P < .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.
UR - https://www.scopus.com/pages/publications/85072110353
U2 - 10.1182/bloodadvances.2019000226
DO - 10.1182/bloodadvances.2019000226
M3 - Article
C2 - 31471322
AN - SCOPUS:85072110353
SN - 2473-9529
VL - 3
SP - 2525
EP - 2536
JO - Blood Advances
JF - Blood Advances
IS - 17
ER -