Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant

Maxim Norkin; Bronwen E Shaw; Ruta Brazauskas; Heather R Tecca; Helen L Leather; Juan Gea-Banacloche; Rammurti Kamble; Zachariah DeFilipp; David A Jacobsohn; Olle Ringden; Yoshihiro Inamoto; Kimberly Kasow; David Buchbinder; Peter Shaw; Peiman Hematti; Raquel Schears; Sherif M Badawy; Hillard M Lazarus; Neel Bhatt; Biljana Horn; Saurabh Chhabra; Kristin Page; Betty Hamilton; Gerhard C Hildebrandt; Jean A Yared; Vaibhav Agrawal; Amer Beitinjaneh; Navneet Majhail; Tamila Kindwall-Keller; Richard F Olsson; Helene Schoemans; Robert Peter Gale; Siddhartha Ganguly; Ibrahim Ahmed; Harry C Schouten; Jane 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

doi:10.1016/j.bbmt.2018.09.031

Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant

Maxim Norkin, Bronwen E Shaw, Ruta Brazauskas, Heather R Tecca, Helen L Leather, Juan Gea-Banacloche, Rammurti Kamble, Zachariah DeFilipp, David A Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M Badawy, Hillard M Lazarus, Neel Bhatt, Biljana HornSaurabh Chhabra, Kristin Page, Betty Hamilton, Gerhard C Hildebrandt, Jean A Yared, Vaibhav Agrawal, Amer Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim Ahmed, Harry C Schouten, Jane 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

Pediatrics

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

18 Scopus citations

Abstract

BACKGROUND: We analyzed late fatal infections (LFI) in allogeneic stem cell transplant (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research.

METHODS: We analyzed the incidence, infection types and risk factors contributing to LFI in 10336 adult and 5088 pediatric subjects surviving ≥2 years after first HCT without relapse.

RESULTS: Among 2245 adult and 377 pediatric subjects who died, infections were a primary or contributory cause of death in 687(31%) and 110(29%) subjects, respectively. At 12 years post-HCT cumulative incidence of LFIs was 6.4 % (95% confidence interval[CI]:5.8-7.0%) in adults as compared with 1.8% (95%CI:1.4-2.3%) in pediatric subjects, p<0.001. In adults, the two most significant risks for developing LFI were increasing age (20-39, 40-54 and ≥ 55 vs 18-19 years) with hazard ratio (HR) of 3.12 (95%CI:1.33-7.32), 3.86 (95%CI:1.66-8.95) and 5.49 (95%CI:2.32-12.99) and a history of chronic GVHD (cGVHD) with ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD with HR 3.87 (95%CI:2.59-5.78), respectively. In pediatric subjects, the three most significant risks for developing LFI were a history of cGVHD with (HR 9.49, 95%CI:4.39-20.51) or without (HR 2.7,95%CI:1.05-7.43) ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function as compared to diagnosis of acute myeloid leukemia (AML) (HR 2.30, 95%CI:1.19-4.42) and age >10 years (HR 1.92, 95%CI:1.15-3.2).

CONCLUSION: This study emphasizes the importance of continued vigilance for late infections after HCT and support strategies aimed to decrease the risk of cGVHD.

Original language	English (US)
Journal	Biology of Blood and Marrow Transplantation
DOIs	https://doi.org/10.1016/j.bbmt.2018.09.031
State	E-pub ahead of print - Oct 1 2018

Access to Document

10.1016/j.bbmt.2018.09.031

Cite this

Norkin, M., Shaw, B. E., Brazauskas, R., Tecca, H. R., Leather, H. L., Gea-Banacloche, J., Kamble, R., DeFilipp, Z., Jacobsohn, D. A., Ringden, O., Inamoto, Y., Kasow, K., Buchbinder, D., Shaw, P., Hematti, P., Schears, R., Badawy, S. M., Lazarus, H. M., Bhatt, N., ... Savani, B. N. (2018). Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant. Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2018.09.031

@article{e7d1c994b1044582ad528d5bf470d1fd,

title = "Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant",

abstract = "BACKGROUND: We analyzed late fatal infections (LFI) in allogeneic stem cell transplant (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research.METHODS: We analyzed the incidence, infection types and risk factors contributing to LFI in 10336 adult and 5088 pediatric subjects surviving ≥2 years after first HCT without relapse.RESULTS: Among 2245 adult and 377 pediatric subjects who died, infections were a primary or contributory cause of death in 687(31%) and 110(29%) subjects, respectively. At 12 years post-HCT cumulative incidence of LFIs was 6.4 % (95% confidence interval[CI]:5.8-7.0%) in adults as compared with 1.8% (95%CI:1.4-2.3%) in pediatric subjects, p<0.001. In adults, the two most significant risks for developing LFI were increasing age (20-39, 40-54 and ≥ 55 vs 18-19 years) with hazard ratio (HR) of 3.12 (95%CI:1.33-7.32), 3.86 (95%CI:1.66-8.95) and 5.49 (95%CI:2.32-12.99) and a history of chronic GVHD (cGVHD) with ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD with HR 3.87 (95%CI:2.59-5.78), respectively. In pediatric subjects, the three most significant risks for developing LFI were a history of cGVHD with (HR 9.49, 95%CI:4.39-20.51) or without (HR 2.7,95%CI:1.05-7.43) ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function as compared to diagnosis of acute myeloid leukemia (AML) (HR 2.30, 95%CI:1.19-4.42) and age >10 years (HR 1.92, 95%CI:1.15-3.2).CONCLUSION: This study emphasizes the importance of continued vigilance for late infections after HCT and support strategies aimed to decrease 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 Rammurti Kamble and Zachariah DeFilipp and Jacobsohn, {David A} and Olle Ringden and Yoshihiro Inamoto and Kimberly Kasow 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 Kristin Page and Betty Hamilton and Hildebrandt, {Gerhard C} and Yared, {Jean A} and Vaibhav Agrawal and Amer Beitinjaneh and Navneet Majhail and Tamila Kindwall-Keller and Olsson, {Richard F} and Helene Schoemans and Gale, {Robert Peter} and Siddhartha Ganguly and Ibrahim Ahmed and Schouten, {Harry C} and Jane Liesveld 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}",

note = "Copyright {\textcopyright} 2018. Published by Elsevier Inc.",

year = "2018",

month = oct,

day = "1",

doi = "10.1016/j.bbmt.2018.09.031",

language = "English (US)",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier Inc.",

}

Norkin, M, Shaw, BE, Brazauskas, R, Tecca, HR, Leather, HL, Gea-Banacloche, J, Kamble, R, DeFilipp, Z, Jacobsohn, DA, Ringden, O, Inamoto, Y, Kasow, K, Buchbinder, D, Shaw, P, Hematti, P, Schears, R, Badawy, SM, Lazarus, HM, Bhatt, N, Horn, B, Chhabra, S, Page, K, Hamilton, B, Hildebrandt, GC, Yared, JA, Agrawal, V, Beitinjaneh, A, Majhail, N, Kindwall-Keller, T, Olsson, RF, Schoemans, H, Gale, RP, Ganguly, S, Ahmed, I, Schouten, HC, 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 2018, 'Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2018.09.031

TY - JOUR

T1 - Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant

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

AU - DeFilipp, Zachariah

AU - Jacobsohn, David A

AU - Ringden, Olle

AU - Inamoto, Yoshihiro

AU - 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 - Page, Kristin

AU - Hamilton, Betty

AU - Hildebrandt, Gerhard C

AU - Yared, Jean A

AU - Agrawal, Vaibhav

AU - Beitinjaneh, Amer

AU - Majhail, Navneet

AU - Kindwall-Keller, Tamila

AU - Olsson, Richard F

AU - Schoemans, Helene

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Ahmed, Ibrahim

AU - Schouten, Harry C

AU - 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

PY - 2018/10/1

Y1 - 2018/10/1

N2 - BACKGROUND: We analyzed late fatal infections (LFI) in allogeneic stem cell transplant (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research.METHODS: We analyzed the incidence, infection types and risk factors contributing to LFI in 10336 adult and 5088 pediatric subjects surviving ≥2 years after first HCT without relapse.RESULTS: Among 2245 adult and 377 pediatric subjects who died, infections were a primary or contributory cause of death in 687(31%) and 110(29%) subjects, respectively. At 12 years post-HCT cumulative incidence of LFIs was 6.4 % (95% confidence interval[CI]:5.8-7.0%) in adults as compared with 1.8% (95%CI:1.4-2.3%) in pediatric subjects, p<0.001. In adults, the two most significant risks for developing LFI were increasing age (20-39, 40-54 and ≥ 55 vs 18-19 years) with hazard ratio (HR) of 3.12 (95%CI:1.33-7.32), 3.86 (95%CI:1.66-8.95) and 5.49 (95%CI:2.32-12.99) and a history of chronic GVHD (cGVHD) with ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD with HR 3.87 (95%CI:2.59-5.78), respectively. In pediatric subjects, the three most significant risks for developing LFI were a history of cGVHD with (HR 9.49, 95%CI:4.39-20.51) or without (HR 2.7,95%CI:1.05-7.43) ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function as compared to diagnosis of acute myeloid leukemia (AML) (HR 2.30, 95%CI:1.19-4.42) and age >10 years (HR 1.92, 95%CI:1.15-3.2).CONCLUSION: This study emphasizes the importance of continued vigilance for late infections after HCT and support strategies aimed to decrease the risk of cGVHD.

AB - BACKGROUND: We analyzed late fatal infections (LFI) in allogeneic stem cell transplant (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research.METHODS: We analyzed the incidence, infection types and risk factors contributing to LFI in 10336 adult and 5088 pediatric subjects surviving ≥2 years after first HCT without relapse.RESULTS: Among 2245 adult and 377 pediatric subjects who died, infections were a primary or contributory cause of death in 687(31%) and 110(29%) subjects, respectively. At 12 years post-HCT cumulative incidence of LFIs was 6.4 % (95% confidence interval[CI]:5.8-7.0%) in adults as compared with 1.8% (95%CI:1.4-2.3%) in pediatric subjects, p<0.001. In adults, the two most significant risks for developing LFI were increasing age (20-39, 40-54 and ≥ 55 vs 18-19 years) with hazard ratio (HR) of 3.12 (95%CI:1.33-7.32), 3.86 (95%CI:1.66-8.95) and 5.49 (95%CI:2.32-12.99) and a history of chronic GVHD (cGVHD) with ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD with HR 3.87 (95%CI:2.59-5.78), respectively. In pediatric subjects, the three most significant risks for developing LFI were a history of cGVHD with (HR 9.49, 95%CI:4.39-20.51) or without (HR 2.7,95%CI:1.05-7.43) ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function as compared to diagnosis of acute myeloid leukemia (AML) (HR 2.30, 95%CI:1.19-4.42) and age >10 years (HR 1.92, 95%CI:1.15-3.2).CONCLUSION: This study emphasizes the importance of continued vigilance for late infections after HCT and support strategies aimed to decrease the risk of cGVHD.

U2 - 10.1016/j.bbmt.2018.09.031

DO - 10.1016/j.bbmt.2018.09.031

M3 - Article

C2 - 30287390

SN - 1083-8791

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

ER -

Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant

Abstract

Access to Document

Fingerprint

Cite this