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

doi:10.1016/j.bbmt.2018.11.018

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

Pediatrics

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

22 Scopus citations

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 language	English (US)
Pages (from-to)	756-763
Number of pages	8
Journal	Biology of Blood and Marrow Transplantation
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.bbmt.2018.11.018
State	Published - Apr 2019

Funding

Financial disclosure: L.P.S. was supported by a National Research Service Award Post-Doctoral Traineeship (5T32 HS000032-28) from the Agency for Healthcare Research and Quality, sponsored by the Cecil G. Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. C.S. is a Stanford Child Health Research Institute Pete and Arline Harman Fellow and received funding from the National Institutes of Health (T32-DK098132). A.D.S. was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (5KL2 TR001115). Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: L.S. and M.K. performed the literature searches, designed the study, and analyzed the data and take full responsibility for the integrity of the data and the analysis. J.K. A.S. V.P. T.D. S.P. K.P. and R.V. collected data. L.S. P.M. C.S. A.S. M.A. W.S. and P.S. interpreted the data. L.S. prepared the first draft of the manuscript. All authors critically reviewed this first draft and contributed to subsequent versions of the manuscript and approved submission of the final version of the manuscript. Financial disclosure: L.P.S. was supported by a National Research Service Award Post-Doctoral Traineeship ( 5T32 HS000032-28 ) from the Agency for Healthcare Research and Quality, sponsored by the Cecil G. Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. C.S. is a Stanford Child Health Research Institute Pete and Arline Harman Fellow and received funding from the National Institutes of Health ( T32-DK098132 ). A.D.S. was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health ( 5KL2 TR001115 ).

Keywords

Aspergillosis
Children
Introduction
Race
Survival
Umbilical cord blood transplantation

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2018.11.018

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Spees, L. P., Martin, P. L., Kurtzberg, J., Stokhuyzen, A., McGill, L., Prasad, V. K., Driscoll, T. A., Parikh, S. H., Page, K. M., Vinesett, R., Severyn, C., Sung, A. D., Proia, A. D., Jenkins, K., Arshad, M., Steinbach, W. J., Seed, P. C., & 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

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

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doi = "10.1016/j.bbmt.2018.11.018",

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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

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AU - Spees, Lisa P.

AU - Martin, Paul L.

AU - Kurtzberg, Joanne

AU - Stokhuyzen, Andre

AU - McGill, Lauren

AU - Prasad, Vinod K.

AU - Driscoll, Timothy A.

AU - Parikh, Suhag H.

AU - Page, Kristin M.

AU - Vinesett, Richard

AU - Severyn, Christopher

AU - Sung, Anthony D.

AU - Proia, Alan D.

AU - Jenkins, Kirsten

AU - Arshad, Mehreen

AU - Steinbach, William J.

AU - Seed, Patrick Casey

AU - Kelly, Matthew S.

PY - 2019/4

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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.

AB - 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.

KW - Aspergillosis

KW - Children

KW - Introduction

KW - Race

KW - Survival

KW - Umbilical cord blood transplantation

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

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