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

Suhag H. Parikh, Adam Mendizabal, Cara L. Benjamin, Krishna V. Komanduri, Jeyaraj Antony, Aleksandra Petrovic, Gregory Hale, Timothy A. Driscoll, Paul L. Martin, Kristin M. Page, Ketti Flickinger, Jerelyn Moffet, Donna Niedzwiecki, Joanne Kurtzberg, Paul Szabolcs

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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 2.8years, 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× 107/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 20days, with the majority sustaining>95% donor chimerism at 1year. 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 31months 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).

Original languageEnglish (US)
Pages (from-to)326-336
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Issue number3
StatePublished - Mar 2014


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

ASJC Scopus subject areas

  • Transplantation
  • Hematology


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