Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant

Suhag H. Parikh, Prakash Satwani, Kwang Woo Ahn, Natasha A. Sahr, Caitrin Fretham, Allistair A. Abraham, Vaibhav Agrawal, Jeffery J. Auletta, Hisham Abdel-Azim, Edward Copelan, Miguel Angel Diaz, Christopher C. Dvorak, Haydar A. Frangoul, Cesar O. Freytes, Shahinaz M. Gadalla, Robert Peter Gale, Biju George, Usama Gergis, Shahrukh Hashmi, Peiman HemattiGerhard C. Hildebrandt, Amy K. Keating, Hillard M. Lazarus, Kasiani C. Myers, Richard F. Olsson, Timothy Prestidge, Seth J. Rotz, Bipin N. Savani, Evan Shereck, Kirsten M. Williams, Baldeep Wirk, Marcelo C. Pasquini, Alison W. Loren

Research output: Contribution to journalArticle

Abstract

Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: Survival trends, disease relapse, and toxicity. Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P =.007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P =.01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

Original languageEnglish (US)
JournalJAMA Pediatrics
DOIs
StatePublished - Jan 1 2019

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Transplants
Recurrence
Survival Rate
Hepatic Veno-Occlusive Disease
Bone Marrow
Donor Selection
Survival
Survival Analysis
HLA Antigens
Siblings
Leukemia
Cohort Studies
Outcome Assessment (Health Care)
Incidence
Research

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Parikh, S. H., Satwani, P., Ahn, K. W., Sahr, N. A., Fretham, C., Abraham, A. A., ... Loren, A. W. (2019). Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2019.0081

Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant. / Parikh, Suhag H.; Satwani, Prakash; Ahn, Kwang Woo; Sahr, Natasha A.; Fretham, Caitrin; Abraham, Allistair A.; Agrawal, Vaibhav; Auletta, Jeffery J.; Abdel-Azim, Hisham; Copelan, Edward; Diaz, Miguel Angel; Dvorak, Christopher C.; Frangoul, Haydar A.; Freytes, Cesar O.; Gadalla, Shahinaz M.; Gale, Robert Peter; George, Biju; Gergis, Usama; Hashmi, Shahrukh; Hematti, Peiman; Hildebrandt, Gerhard C.; Keating, Amy K.; Lazarus, Hillard M.; Myers, Kasiani C.; Olsson, Richard F.; Prestidge, Timothy; Rotz, Seth J.; Savani, Bipin N.; Shereck, Evan; Williams, Kirsten M.; Wirk, Baldeep; Pasquini, Marcelo C.; Loren, Alison W.

In: JAMA Pediatrics, 01.01.2019.

Research output: Contribution to journalArticle

Parikh, SH, Satwani, P, Ahn, KW, Sahr, NA, Fretham, C, Abraham, AA, Agrawal, V, Auletta, JJ, Abdel-Azim, H, Copelan, E, Diaz, MA, Dvorak, CC, Frangoul, HA, Freytes, CO, Gadalla, SM, Gale, RP, George, B, Gergis, U, Hashmi, S, Hematti, P, Hildebrandt, GC, Keating, AK, Lazarus, HM, Myers, KC, Olsson, RF, Prestidge, T, Rotz, SJ, Savani, BN, Shereck, E, Williams, KM, Wirk, B, Pasquini, MC & Loren, AW 2019, 'Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant', JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2019.0081
Parikh, Suhag H. ; Satwani, Prakash ; Ahn, Kwang Woo ; Sahr, Natasha A. ; Fretham, Caitrin ; Abraham, Allistair A. ; Agrawal, Vaibhav ; Auletta, Jeffery J. ; Abdel-Azim, Hisham ; Copelan, Edward ; Diaz, Miguel Angel ; Dvorak, Christopher C. ; Frangoul, Haydar A. ; Freytes, Cesar O. ; Gadalla, Shahinaz M. ; Gale, Robert Peter ; George, Biju ; Gergis, Usama ; Hashmi, Shahrukh ; Hematti, Peiman ; Hildebrandt, Gerhard C. ; Keating, Amy K. ; Lazarus, Hillard M. ; Myers, Kasiani C. ; Olsson, Richard F. ; Prestidge, Timothy ; Rotz, Seth J. ; Savani, Bipin N. ; Shereck, Evan ; Williams, Kirsten M. ; Wirk, Baldeep ; Pasquini, Marcelo C. ; Loren, Alison W. / Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant. In: JAMA Pediatrics. 2019.
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title = "Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant",
abstract = "Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: Survival trends, disease relapse, and toxicity. Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95{\%} CI, 0.63-0.93]; P =.007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0{\%}]; 2005-2009, 503/699 [72.0{\%}]; and 2010-2014, 555/750 [74.0{\%}]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8{\%}]; 2005-2009, 104/161 [64.6{\%}]; and 2010-2014, 66/112 [58.9{\%}]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19{\%} [95{\%} CI, 14{\%}-25{\%}]; 2005-2009, 23{\%} [95{\%} CI, 17{\%}-30{\%}]; 2010-2014, 36{\%} [95{\%} CI, 27{\%}-46{\%}]; P =.01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13{\%} (95{\%} CI, 11{\%}-16{\%}) of infants with nonmalignant diseases and 32{\%} (95{\%} CI, 22{\%}-42{\%}) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.",
author = "Parikh, {Suhag H.} and Prakash Satwani and Ahn, {Kwang Woo} and Sahr, {Natasha A.} and Caitrin Fretham and Abraham, {Allistair A.} and Vaibhav Agrawal and Auletta, {Jeffery J.} and Hisham Abdel-Azim and Edward Copelan and Diaz, {Miguel Angel} and Dvorak, {Christopher C.} and Frangoul, {Haydar A.} and Freytes, {Cesar O.} and Gadalla, {Shahinaz M.} and Gale, {Robert Peter} and Biju George and Usama Gergis and Shahrukh Hashmi and Peiman Hematti and Hildebrandt, {Gerhard C.} and Keating, {Amy K.} and Lazarus, {Hillard M.} and Myers, {Kasiani C.} and Olsson, {Richard F.} and Timothy Prestidge and Rotz, {Seth J.} and Savani, {Bipin N.} and Evan Shereck and Williams, {Kirsten M.} and Baldeep Wirk and Pasquini, {Marcelo C.} and Loren, {Alison W.}",
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journal = "JAMA Pediatrics",
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TY - JOUR

T1 - Survival Trends in Infants Undergoing Allogeneic Hematopoietic Cell Transplant

AU - Parikh, Suhag H.

AU - Satwani, Prakash

AU - Ahn, Kwang Woo

AU - Sahr, Natasha A.

AU - Fretham, Caitrin

AU - Abraham, Allistair A.

AU - Agrawal, Vaibhav

AU - Auletta, Jeffery J.

AU - Abdel-Azim, Hisham

AU - Copelan, Edward

AU - Diaz, Miguel Angel

AU - Dvorak, Christopher C.

AU - Frangoul, Haydar A.

AU - Freytes, Cesar O.

AU - Gadalla, Shahinaz M.

AU - Gale, Robert Peter

AU - George, Biju

AU - Gergis, Usama

AU - Hashmi, Shahrukh

AU - Hematti, Peiman

AU - Hildebrandt, Gerhard C.

AU - Keating, Amy K.

AU - Lazarus, Hillard M.

AU - Myers, Kasiani C.

AU - Olsson, Richard F.

AU - Prestidge, Timothy

AU - Rotz, Seth J.

AU - Savani, Bipin N.

AU - Shereck, Evan

AU - Williams, Kirsten M.

AU - Wirk, Baldeep

AU - Pasquini, Marcelo C.

AU - Loren, Alison W.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: Survival trends, disease relapse, and toxicity. Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P =.007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P =.01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

AB - Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: Survival trends, disease relapse, and toxicity. Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P =.007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P =.01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

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