Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation

Maxim Norkin, Bronwen E. Shaw, Ruta Brazauskas, Heather R. Tecca, Helen L. Leather, Juan Gea-Banacloche, Rammurti T. Kamble, Zachariah DeFilipp, David A. Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly A. Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M. Badawy, Hillard M. Lazarus, Neel Bhatt, Biljana HornSaurabh Chhabra, Kristin M. Page, Betty Hamilton, Gerhard C. Hildebrandt, Jean A. Yared, Vaibhav Agrawal, Amer M. Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F. Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim A. Ahmed, Harry C. Schouten, Jane L. Liesveld, Nandita Khera, Amir Steinberg, Ami J. Shah, Melhem Solh, David I. Marks, Witold Rybka, Mahmoud Aljurf, Andrew C. Dietz, Usama Gergis, Biju George, Sachiko Seo, Mary E.D. Flowers, Minoo Battiwalla, Bipin N. Savani, Marcie L. Riches, John R. Wingard

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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-HCT, 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-HCT 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.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number2
DOIs
StatePublished - Feb 2019

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Cell Transplantation
Infection
Confidence Intervals
Pediatrics
Incidence
Stem Cell Transplantation
Cause of Death
Bone Marrow
Transplants
Recurrence
Research

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Norkin, M., Shaw, B. E., Brazauskas, R., Tecca, H. R., Leather, H. L., Gea-Banacloche, J., ... Wingard, J. R. (2019). Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 25(2), 362-368. https://doi.org/10.1016/j.bbmt.2018.09.031
Norkin, Maxim ; Shaw, Bronwen E. ; Brazauskas, Ruta ; Tecca, Heather R. ; Leather, Helen L. ; Gea-Banacloche, Juan ; T. Kamble, Rammurti ; DeFilipp, Zachariah ; Jacobsohn, David A. ; Ringden, Olle ; Inamoto, Yoshihiro ; A. Kasow, Kimberly ; Buchbinder, David ; Shaw, Peter ; Hematti, Peiman ; Schears, Raquel ; Badawy, Sherif M. ; Lazarus, Hillard M. ; Bhatt, Neel ; Horn, Biljana ; Chhabra, Saurabh ; M. Page, Kristin ; Hamilton, Betty ; Hildebrandt, Gerhard C. ; Yared, Jean A. ; Agrawal, Vaibhav ; M. Beitinjaneh, Amer ; Majhail, Navneet ; Kindwall-Keller, Tamila ; Olsson, Richard F. ; Schoemans, Helene ; Gale, Robert Peter ; Ganguly, Siddhartha ; A. Ahmed, Ibrahim ; Schouten, Harry C. ; L. Liesveld, Jane ; Khera, Nandita ; Steinberg, Amir ; Shah, Ami J. ; Solh, Melhem ; Marks, David I. ; Rybka, Witold ; Aljurf, Mahmoud ; Dietz, Andrew C. ; Gergis, Usama ; George, Biju ; Seo, Sachiko ; Flowers, Mary E.D. ; Battiwalla, Minoo ; Savani, Bipin N. ; Riches, Marcie L. ; Wingard, John R. / Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 2. pp. 362-368.
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title = "Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation",
abstract = "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-HCT, 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-HCT 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.",
author = "Maxim Norkin and Shaw, {Bronwen E.} and Ruta Brazauskas and Tecca, {Heather R.} and Leather, {Helen L.} and Juan Gea-Banacloche and {T. Kamble}, Rammurti and Zachariah DeFilipp and Jacobsohn, {David A.} and Olle Ringden and Yoshihiro Inamoto and {A. Kasow}, Kimberly and David Buchbinder and Peter Shaw and Peiman Hematti and Raquel Schears and Badawy, {Sherif M.} and Lazarus, {Hillard M.} and Neel Bhatt and Biljana Horn and Saurabh Chhabra and {M. Page}, Kristin and Betty Hamilton and Hildebrandt, {Gerhard C.} and Yared, {Jean A.} and Vaibhav Agrawal and {M. Beitinjaneh}, Amer and Navneet Majhail and Tamila Kindwall-Keller and Olsson, {Richard F.} and Helene Schoemans and Gale, {Robert Peter} and Siddhartha Ganguly and {A. Ahmed}, Ibrahim and Schouten, {Harry C.} and {L. Liesveld}, Jane and Nandita Khera and Amir Steinberg and Shah, {Ami J.} and Melhem Solh and Marks, {David I.} and Witold Rybka and Mahmoud Aljurf and Dietz, {Andrew C.} and Usama Gergis and Biju George and Sachiko Seo and Flowers, {Mary E.D.} and Minoo Battiwalla and Savani, {Bipin N.} and Riches, {Marcie L.} and Wingard, {John R.}",
year = "2019",
month = "2",
doi = "10.1016/j.bbmt.2018.09.031",
language = "English (US)",
volume = "25",
pages = "362--368",
journal = "Biology of Blood and Marrow Transplantation",
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Norkin, M, Shaw, BE, Brazauskas, R, Tecca, HR, Leather, HL, Gea-Banacloche, J, T. Kamble, R, DeFilipp, Z, Jacobsohn, DA, Ringden, O, Inamoto, Y, A. Kasow, K, Buchbinder, D, Shaw, P, Hematti, P, Schears, R, Badawy, SM, Lazarus, HM, Bhatt, N, Horn, B, Chhabra, S, M. Page, K, Hamilton, B, Hildebrandt, GC, Yared, JA, Agrawal, V, M. Beitinjaneh, A, Majhail, N, Kindwall-Keller, T, Olsson, RF, Schoemans, H, Gale, RP, Ganguly, S, A. Ahmed, I, Schouten, HC, L. Liesveld, J, Khera, N, Steinberg, A, Shah, AJ, Solh, M, Marks, DI, Rybka, W, Aljurf, M, Dietz, AC, Gergis, U, George, B, Seo, S, Flowers, MED, Battiwalla, M, Savani, BN, Riches, ML & Wingard, JR 2019, 'Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 25, no. 2, pp. 362-368. https://doi.org/10.1016/j.bbmt.2018.09.031

Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation. / Norkin, Maxim; Shaw, Bronwen E.; Brazauskas, Ruta; Tecca, Heather R.; Leather, Helen L.; Gea-Banacloche, Juan; T. Kamble, Rammurti; DeFilipp, Zachariah; Jacobsohn, David A.; Ringden, Olle; Inamoto, Yoshihiro; A. Kasow, Kimberly; Buchbinder, David; Shaw, Peter; Hematti, Peiman; Schears, Raquel; Badawy, Sherif M.; Lazarus, Hillard M.; Bhatt, Neel; Horn, Biljana; Chhabra, Saurabh; M. Page, Kristin; Hamilton, Betty; Hildebrandt, Gerhard C.; Yared, Jean A.; Agrawal, Vaibhav; M. Beitinjaneh, Amer; Majhail, Navneet; Kindwall-Keller, Tamila; Olsson, Richard F.; Schoemans, Helene; Gale, Robert Peter; Ganguly, Siddhartha; A. Ahmed, Ibrahim; Schouten, Harry C.; L. Liesveld, Jane; Khera, Nandita; Steinberg, Amir; Shah, Ami J.; Solh, Melhem; Marks, David I.; Rybka, Witold; Aljurf, Mahmoud; Dietz, Andrew C.; Gergis, Usama; George, Biju; Seo, Sachiko; Flowers, Mary E.D.; Battiwalla, Minoo; Savani, Bipin N.; Riches, Marcie L.; Wingard, John R.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 2, 02.2019, p. 362-368.

Research output: Contribution to journalArticle

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 - T. Kamble, Rammurti

AU - DeFilipp, Zachariah

AU - Jacobsohn, David A.

AU - Ringden, Olle

AU - Inamoto, Yoshihiro

AU - A. Kasow, Kimberly

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 - M. Page, Kristin

AU - Hamilton, Betty

AU - Hildebrandt, Gerhard C.

AU - Yared, Jean A.

AU - Agrawal, Vaibhav

AU - M. Beitinjaneh, Amer

AU - Majhail, Navneet

AU - Kindwall-Keller, Tamila

AU - Olsson, Richard F.

AU - Schoemans, Helene

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - A. Ahmed, Ibrahim

AU - Schouten, Harry C.

AU - L. Liesveld, Jane

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.

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-HCT, 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-HCT 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.

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-HCT, 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-HCT 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.

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