Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1

Celalettin Ustun; Soyoung Kim; Min Chen; Amer M. Beitinjaneh; Valerie I. Brown; Parastoo B. Dahi; Andrew Daly; Miguel Angel Diaz; Cesar O. Freytes; Siddhartha Ganguly; Shahrukh Hashmi; Gerhard C. Hildebrandt; Hillard M. Lazarus; Taiga Nishihori; Richard F. Olsson; Kristin M. Page; Genovefa Papanicolaou; Ayman Saad; Sachiko Seo; Basem M. William; John R. Wingard; Baldeep Wirk; Jean A. Yared; Miguel Angel Perales; Jeffery J. Auletta; Krishna V. Komanduri; Caroline A. Lindemans; Marcie L. Riches

doi:10.1182/bloodadvances.2019000226

Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1

Celalettin Ustun
, Soyoung Kim
, Min Chen
, Amer M. Beitinjaneh
, Valerie I. Brown
, Parastoo B. Dahi
, Andrew Daly
, Miguel Angel Diaz
, Cesar O. Freytes
, Siddhartha Ganguly
, Shahrukh Hashmi
, Gerhard C. Hildebrandt
, Hillard M. Lazarus
, Taiga Nishihori
, Richard F. Olsson
, Kristin M. Page
, Genovefa Papanicolaou
, Ayman Saad
, Sachiko Seo
, Basem M. William

John R. Wingard, Baldeep Wirk, Jean A. Yared, Miguel Angel Perales, Jeffery J. Auletta, Krishna V. Komanduri, Caroline A. Lindemans, Marcie L. Riches

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2525-2536
Number of pages	12
Journal	Blood advances
Volume	3
Issue number	17
DOIs	https://doi.org/10.1182/bloodadvances.2019000226
State	Published - Sep 10 2019

Bibliographical note

Publisher Copyright:
© 2019 by The American Society of Hematology.

Funding

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. 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

Funders	Funder number
Actinium Pharmaceuticals, Inc.
AMGEN, Inc.
Amneal Biosciences, *Angiocrine Bioscience
Angiocrine Bioscience, Inc.
Cerus Corporation
Department of the Navy
Gamida Cell Ltd. Cell Therapy Technologies
Incyte Corporation
Janssen Scientific Affairs LLC
MesoScale Diagnostics, Inc.
Mesoblast
National Institues of Health	HHSH250201200016C
Neovii Biotech NA, Inc.
PIRCHE
Sunesis Pharmaceuticals, Inc.
Swedish Orphan Biovitrum, Inc.
Telomere Diagnostics, Inc.
US Government Accountability Office
National Institutes of Health (NIH)
U.S. Department of Defense
Office of Naval Research Naval Academy
Foundation for the National Institutes of Health
U.S. Department of Health and Human Services	N00014-17-1-2388, N0014-17-1-2850
U.S. Department of Health and Human Services
National Heart, Lung, and Blood Institute (NHLBI)	U10HL069294
National Heart, Lung, and Blood Institute (NHLBI)
National Childhood Cancer Registry – National Cancer Institute
National Institute of Allergy and Infectious Diseases
Health Resources and Services Administration
Be The Match Foundation
AMGen
Bristol-Myers Squibb
Pfizer
Merck
Gilead Sciences
Fred Hutchinson Cancer Research Center
St. Baldrick's Foundation
Patient-Centered Outcomes Research Institute
Spectrum Pharmaceuticals
Celgene
U.S. Public Health Service	5U24CA076518
U.S. Public Health Service
Minnesota State University-Mankato
Astellas Pharma Global Development Incorporated
Novartis Pharmaceuticals Corporation
Otsuka America Pharmaceutical
Takeda Oncology
Sanofi Genzyme
Pharmacyclics, Inc.
MedImmune
medac GmbH

ASJC Scopus subject areas

Hematology

Access to Document

10.1182/bloodadvances.2019000226

Cite this

Ustun, C., Kim, S., Chen, M., Beitinjaneh, A. M., Brown, V. I., Dahi, P. B., Daly, A., Diaz, M. A., Freytes, C. O., Ganguly, S., Hashmi, S., Hildebrandt, G. C., Lazarus, H. M., Nishihori, T., Olsson, R. F., Page, K. M., Papanicolaou, G., Saad, A., Seo, S., ... Riches, M. L. (2019). Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1. Blood advances, 3(17), 2525-2536. https://doi.org/10.1182/bloodadvances.2019000226

@article{ac95c9f92ef44e3b9f1319b18bf23462,

title = "Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1",

abstract = "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.",

author = "Celalettin Ustun and Soyoung Kim and Min Chen and Beitinjaneh, \{Amer M.\} and Brown, \{Valerie I.\} and Dahi, \{Parastoo B.\} and Andrew Daly and Diaz, \{Miguel Angel\} and Freytes, \{Cesar O.\} and Siddhartha Ganguly and Shahrukh Hashmi and Hildebrandt, \{Gerhard C.\} and Lazarus, \{Hillard M.\} and Taiga Nishihori and Olsson, \{Richard F.\} and Page, \{Kristin M.\} and Genovefa Papanicolaou and Ayman Saad and Sachiko Seo and William, \{Basem M.\} and Wingard, \{John R.\} and Baldeep Wirk and Yared, \{Jean A.\} and Perales, \{Miguel Angel\} and Auletta, \{Jeffery J.\} and Komanduri, \{Krishna V.\} and Lindemans, \{Caroline A.\} and Riches, \{Marcie L.\}",

note = "Publisher Copyright: {\textcopyright} 2019 by The American Society of Hematology.",

year = "2019",

month = sep,

day = "10",

doi = "10.1182/bloodadvances.2019000226",

language = "English",

volume = "3",

pages = "2525--2536",

number = "17",

}

Ustun, C, Kim, S, Chen, M, Beitinjaneh, AM, Brown, VI, Dahi, PB, Daly, A, Diaz, MA, Freytes, CO, Ganguly, S, Hashmi, S, Hildebrandt, GC, Lazarus, HM, Nishihori, T, Olsson, RF, Page, KM, Papanicolaou, G, Saad, A, Seo, S, William, BM, Wingard, JR, Wirk, B, Yared, JA, Perales, MA, Auletta, JJ, Komanduri, KV, Lindemans, CA & Riches, ML 2019, 'Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1', Blood advances, vol. 3, no. 17, pp. 2525-2536. https://doi.org/10.1182/bloodadvances.2019000226

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.

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

UR - https://www.scopus.com/pages/publications/85072110353#tab=citedBy

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 -

Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this