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Biol Blood Marrow Transplant. 2014 Mar;20(3):326-36. doi: 10.1016/j.bbmt.2013.11.021. Epub 2013 Dec 1.

A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases.

Author information

1
Pediatric Blood and Marrow Transplantation Program, Duke University Medical Center, Durham, North Carolina. Electronic address: suhag.parikh@duke.edu.
2
The Emmes Corporation, Rockville, Maryland.
3
Adult Stem Cell Transplant Program, Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida.
4
Division of Blood and Marrow Transplantation and Cellular Therapies, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
5
Blood and Marrow Transplant Program, All Children's Hospital, St. Petersburg, Florida.
6
Pediatric Blood and Marrow Transplantation Program, Duke University Medical Center, Durham, North Carolina.

Abstract

Reduced-intensity conditioning (RIC) regimens have the potential to decrease transplantation-related morbidity and mortality. However, engraftment failure has been prohibitively high after RIC unrelated umbilical cord blood transplantation (UCBT) in chemotherapy-naïve children with nonmalignant diseases (NMD). Twenty-two children with a median age of 2.8 years, many with severe comorbidities and prior viral infections, were enrolled in a novel RIC protocol consisting of hydroxyurea, alemtuzumab, fludarabine, melphalan, and thiotepa followed by single UCBT. Patients underwent transplantation for inherited metabolic disorders (n = 8), primary immunodeficiencies (n = 9), hemoglobinopathies (n = 4) and Diamond Blackfan anemia (n = 1). Most umbilical cord blood (UCB) units were HLA-mismatched with median infused total nucleated cell dose of 7.9 × 10(7)/kg. No serious organ toxicities were attributable to the regimen. The cumulative incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65% to 100%) in a median of 20 days, with the majority sustaining > 95% donor chimerism at 1 year. Cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV by day 180 was 27.3% (95% CI, 8.7% to 45.9%) and 13.6% (95 CI, 0% to 27.6%), respectively. Cumulative incidence of extensive chronic GVHD was 9.1% (95% CI, 0% to 20.8%). The primary causes of death were viral infections (n = 3), acute GVHD (n = 1) and transfusion reaction (n = 1). One-year overall and event-free survivals were 77.3% (95% CI, 53.7% to 89.8%) and 68.2% (95% CI, 44.6% to 83.4%) with 31 months median follow-up. This is the first RIC protocol demonstrating durable UCB engraftment in children with NMD. Future risk-based modifications of this regimen could decrease the incidence of viral infections. (www.clinicaltrials.gov/NCT00744692).

KEYWORDS:

Hemophagocytic lymphohistiocytosis (HLH); Nonmalignant diseases; Pediatric disorders; Reduced-intensity conditioning; Thalassemia; Umbilical cord blood transplantation

PMID:
24296492
PMCID:
PMC3947864
DOI:
10.1016/j.bbmt.2013.11.021
[Indexed for MEDLINE]
Free PMC Article
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