TY - JOUR
T1 - Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation
AU - Norkin, Maxim
AU - Shaw, Bronwen E.
AU - Brazauskas, Ruta
AU - Tecca, Heather R.
AU - Leather, Helen L.
AU - Gea-Banacloche, Juan
AU - Kamble, Rammurti T.
AU - DeFilipp, Zachariah
AU - Jacobsohn, David A.
AU - Ringden, Olle
AU - Inamoto, Yoshihiro
AU - Kasow, Kimberly A.
AU - Buchbinder, David
AU - Shaw, Peter
AU - Hematti, Peiman
AU - Schears, Raquel
AU - Badawy, Sherif M.
AU - Lazarus, Hillard M.
AU - Bhatt, Neel
AU - Horn, Biljana
AU - Chhabra, Saurabh
AU - Page, Kristin M.
AU - Hamilton, Betty
AU - Hildebrandt, Gerhard C.
AU - Yared, Jean A.
AU - Agrawal, Vaibhav
AU - Beitinjaneh, Amer M.
AU - Majhai, Navneet
AU - Kindwall-Keller, Tamila
AU - Olsson, Richard F.
AU - Schoemans, Helene
AU - Gale, Robert Peter
AU - Ganguly, Siddhartha
AU - Ahmed, Ibrahim A.
AU - Schouten, Harry C.
AU - Liesveld, Jane L.
AU - Khera, Nandita
AU - Steinberg, Amir
AU - Shah, Ami J.
AU - Solh, Melhem
AU - Marks, David I.
AU - Rybka, Witold
AU - Aljurf, Mahmoud
AU - Dietz, Andrew C.
AU - Gergis, Usama
AU - George, Biju
AU - Seo, Sachiko
AU - Flowers, Mary E. D.
AU - Battiwalla, Minoo
AU - Savani, Bipin N.
AU - Riches, Marcie L.
AU - Wingard, John R.
N1 - 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; Grant/Cooperative Agreement 4U10HL069294 from the NHLBI and NCI; Contract HHSH250201200016C with the Health Resources and Services Administration; Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; *Amgen; *Amneal Biosciences; *Angiocrine Bioscience; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics; Be the Match Foundation; *bluebird bio; *Bristol Myers Squibb Oncology; *Celgene; Cerus; *Chimerix; Fred Hutchinson Cancer Research Center; Gamida Cell; Gilead Sciences; HistoGenetics; Immucor; *Incyte; Janssen Scientific Affairs; *Jazz Pharmaceuticals; Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Medac; MedImmune; Medical College of Wisconsin; *Mediware; *Merck & Company; *Mesoblast; MesoScale Diagnostics; Millennium, the Takeda Oncology Company; *Miltenyi Biotec; National Marrow Donor Program; *Neovii Biotech NA; Novartis Pharmaceuticals; Otsuka Pharmaceuticals; PCORI; *Pfizer; *Pharmacyclics; PIRCHE; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals; St. Baldrick's Foundation; *Sunesis Pharmaceuticals; Swedish Orphan Biovitrum; Takeda Oncology; Telomere Diagnostics; and University of Minnesota. The views expressed in this article do not reflect the official policies or positions of the National Institutes of Health, Department of the Navy, Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. *Corporate members. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: M.N., B.E.S., R.B., H.R.T., M.E.F., M.B., B.N.S., M.L.R., J.G.B., and J.R.W. designed the study and interpreted the results. R.B. and H.R.T. performed data analysis. All authors participated in writing and reviewing the manuscript.
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; Grant/Cooperative Agreement 4U10HL069294 from the NHLBI and NCI; Contract HHSH250201200016C with the Health Resources and Services Administration; Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; *Amgen; *Amneal Biosciences; *Angiocrine Bioscience; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics; Be the Match Foundation; *bluebird bio; *Bristol Myers Squibb Oncology; *Celgene; Cerus; *Chimerix; Fred Hutchinson Cancer Research Center; Gamida Cell; Gilead Sciences; HistoGenetics; Immucor; *Incyte; Janssen Scientific Affairs; *Jazz Pharmaceuticals; Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Medac; MedImmune; Medical College of Wisconsin; *Mediware; *Merck & Company; *Mesoblast; MesoScale Diagnostics; Millennium, the Takeda Oncology Company; *Miltenyi Biotec; National Marrow Donor Program; *Neovii Biotech NA; Novartis Pharmaceuticals; Otsuka Pharmaceuticals; PCORI; *Pfizer; *Pharmacyclics; PIRCHE; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals; St. Baldrick's Foundation; *Sunesis Pharmaceuticals; Swedish Orphan Biovitrum; Takeda Oncology; Telomere Diagnostics; and University of Minnesota. The views expressed in this article do not reflect the official policies or positions of the National Institutes of Health, Department of the Navy, Department of Defense, Health Resources and Services Administration, or any other agency of the US Government.
Publisher Copyright:
© 2018
PY - 2019/2
Y1 - 2019/2
N2 - We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for >= 2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-Ha, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P <.001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and >= 55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-Ha compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD. (C) 2018 American Society for Blood and Marrow Transplantation.
AB - We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for >= 2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-Ha, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P <.001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and >= 55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-Ha compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD. (C) 2018 American Society for Blood and Marrow Transplantation.
KW - Hematopoietic cell transplantation
KW - Infection
KW - Late fatal infection
KW - Adults
KW - Pediatrics
KW - BONE-MARROW-TRANSPLANTATION
KW - IMMUNE RECONSTITUTION
U2 - 10.1016/j.bbmt.2018.09.031
DO - 10.1016/j.bbmt.2018.09.031
M3 - Article
C2 - 30287390
SN - 1083-8791
VL - 25
SP - 362
EP - 368
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 2
ER -