TY - JOUR
T1 - A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases
AU - Parikh, Suhag H.
AU - Mendizabal, Adam
AU - Benjamin, Cara L.
AU - Komanduri, Krishna V.
AU - Antony, Jeyaraj
AU - Petrovic, Aleksandra
AU - Hale, Gregory
AU - Driscoll, Timothy A.
AU - Martin, Paul L.
AU - Page, Kristin M.
AU - Flickinger, Ketti
AU - Moffet, Jerelyn
AU - Niedzwiecki, Donna
AU - Kurtzberg, Joanne
AU - Szabolcs, Paul
N1 - Funding Information:
Financial disclosure: Part of this works was supported by NHLBI R01HL091749 (Multiple principal investigators, K.V.K., P.S.).
PY - 2014/3
Y1 - 2014/3
N2 - 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).
AB - 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).
KW - Hemophagocytic lymphohistiocytosis (HLH)
KW - Nonmalignant diseases
KW - Pediatric disorders
KW - Reduced-intensity conditioning
KW - Thalassemia
KW - Umbilical cord blood transplantation
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U2 - 10.1016/j.bbmt.2013.11.021
DO - 10.1016/j.bbmt.2013.11.021
M3 - Article
C2 - 24296492
AN - SCOPUS:84896709665
VL - 20
SP - 326
EP - 336
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 3
ER -