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Biol Blood Marrow Transplant. 2018 Nov 24. pii: S1083-8791(18)30751-1. doi: 10.1016/j.bbmt.2018.11.018. [Epub ahead of print]

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

Author information

1
The Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC.
2
Division of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, NC.
3
Division of Pediatric Hematology-Oncology, Lucille Packard Children's Hospital, Stanford University, Palo Alto, CA.
4
Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University, Durham, NC.
5
Department of Pathology, Duke University Medical Center, Durham, NC.
6
Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC.
7
Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
8
Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC. Electronic address: matthew.kelly@duke.edu.

Abstract

BACKGROUND:

Infections and graft-versus-host disease 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.

METHODS:

We conducted a retrospective cohort study of children (<18 years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared two-year all-cause and cause-specific mortality during three time periods based on year of transplantation (1995-2001, 2002-2007, 2008-2014). 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.

RESULTS:

During the 20-year study period, 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995-2001 to 30% in 2008-2014 (P=0.0002). White patient race and non-malignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which graft-versus-host disease (18% vs 11%; P=0.06) or graft failure (9% vs 3%; P=0.01) were contributory than white children. Comparing 2008-2014 to 1995-2001, 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 (HR): 0.09; 95% confidence interval (CI): 0.01-0.76]. With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequent infectious causes of death in children after UCBT.

CONCLUSIONS:

Advances in clinical practice over the past 20 years 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.

KEYWORDS:

Aspergillosis; Children; Race; Survival; Umbilical cord blood transplantation

PMID:
30481599
DOI:
10.1016/j.bbmt.2018.11.018

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