Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014)

Lisa P. Spees, Paul L. Martin, Joanne Kurtzberg, Andre Stokhuyzen, Lauren McGill, Vinod K. Prasad, Timothy A. Driscoll, Suhag H. Parikh, Kristin M. Page, Richard Vinesett, Christopher Severyn, Anthony D. Sung, Alan D. Proia, Kirsten Jenkins, Mehreen Arshad, William J. Steinbach, Patrick Casey Seed, Matthew S. Kelly*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P =.0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P =.06) or graft failure (9% versus 3%; P =.01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio,.09; 95% confidence interval,.01 to.76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.

Original languageEnglish (US)
Pages (from-to)756-763
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Fetal Blood
Transplantation
Mortality
Aspergillosis
Graft vs Host Disease
Child Mortality
Infection
Cytomegalovirus
Adenoviridae
Cause of Death
Cohort Studies
Retrospective Studies
Demography
Confidence Intervals
Transplants

Keywords

  • Aspergillosis
  • Children
  • Introduction
  • Race
  • Survival
  • Umbilical cord blood transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Spees, L. P., Martin, P. L., Kurtzberg, J., Stokhuyzen, A., McGill, L., Prasad, V. K., ... Kelly, M. S. (2019). Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014). Biology of Blood and Marrow Transplantation, 25(4), 756-763. https://doi.org/10.1016/j.bbmt.2018.11.018
Spees, Lisa P. ; Martin, Paul L. ; Kurtzberg, Joanne ; Stokhuyzen, Andre ; McGill, Lauren ; Prasad, Vinod K. ; Driscoll, Timothy A. ; Parikh, Suhag H. ; Page, Kristin M. ; Vinesett, Richard ; Severyn, Christopher ; Sung, Anthony D. ; Proia, Alan D. ; Jenkins, Kirsten ; Arshad, Mehreen ; Steinbach, William J. ; Seed, Patrick Casey ; Kelly, Matthew S. / Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014). In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 4. pp. 756-763.
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abstract = "Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48{\%} in 1995 to 2001 to 30{\%} in 2008 to 2014 (P =.0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18{\%} versus 11{\%}; P =.06) or graft failure (9{\%} versus 3{\%}; P =.01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59{\%}) of the reduced mortality was attributable to a reduction in infectious mortality, with 45{\%} specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio,.09; 95{\%} confidence interval,.01 to.76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.",
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Spees, LP, Martin, PL, Kurtzberg, J, Stokhuyzen, A, McGill, L, Prasad, VK, Driscoll, TA, Parikh, SH, Page, KM, Vinesett, R, Severyn, C, Sung, AD, Proia, AD, Jenkins, K, Arshad, M, Steinbach, WJ, Seed, PC & Kelly, MS 2019, 'Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014)', Biology of Blood and Marrow Transplantation, vol. 25, no. 4, pp. 756-763. https://doi.org/10.1016/j.bbmt.2018.11.018

Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014). / Spees, Lisa P.; Martin, Paul L.; Kurtzberg, Joanne; Stokhuyzen, Andre; McGill, Lauren; Prasad, Vinod K.; Driscoll, Timothy A.; Parikh, Suhag H.; Page, Kristin M.; Vinesett, Richard; Severyn, Christopher; Sung, Anthony D.; Proia, Alan D.; Jenkins, Kirsten; Arshad, Mehreen; Steinbach, William J.; Seed, Patrick Casey; Kelly, Matthew S.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 4, 01.04.2019, p. 756-763.

Research output: Contribution to journalArticle

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AU - Driscoll, Timothy A.

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AU - Vinesett, Richard

AU - Severyn, Christopher

AU - Sung, Anthony D.

AU - Proia, Alan D.

AU - Jenkins, Kirsten

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AU - Steinbach, William J.

AU - Seed, Patrick Casey

AU - Kelly, Matthew S.

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N2 - Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P =.0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P =.06) or graft failure (9% versus 3%; P =.01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio,.09; 95% confidence interval,.01 to.76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.

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