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A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases.
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).
Type
Journal articleSubject
Transplantation ChimeraHumans
Anemia, Diamond-Blackfan
Hemoglobinopathies
Metabolic Diseases
Graft vs Host Disease
Common Variable Immunodeficiency
Antineoplastic Agents
HLA Antigens
Transplantation Conditioning
Cord Blood Stem Cell Transplantation
Transplantation, Homologous
Survival Analysis
Graft Survival
Child
Child, Preschool
Infant
Female
Male
Unrelated Donors
Permalink
https://hdl.handle.net/10161/24650Published Version (Please cite this version)
10.1016/j.bbmt.2013.11.021Publication Info
Parikh, Suhag H; Mendizabal, Adam; Benjamin, Cara L; Komanduri, Krishna V; Antony,
Jeyaraj; Petrovic, Aleksandra; ... Szabolcs, Paul (2014). A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood
transplantation in children with nonmalignant diseases. Biology of blood and marrow transplantation : journal of the American Society for
Blood and Marrow Transplantation, 20(3). pp. 326-336. 10.1016/j.bbmt.2013.11.021. Retrieved from https://hdl.handle.net/10161/24650.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Timothy Alan Driscoll
Assistant Professor of Pediatrics
Dr. Driscoll participates in multi-institutional studies for the treatment of high
risk neuroblastoma patients using high dose chemotherapy with stem cell transplant
and the development of new therapies for high risk neuroblastoma patients.
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina
Paul Langlie Martin
Professor of Pediatrics
For most of my career in Pediatric Hematology/Oncology I have focused on the use of
stem cell transplant for the treatment of pediatric leukemias (ALL, AML, CML and JMML)
and other non-malignant blood disorders, such as sickle cell disease, hemaphagocytic
disorders, Wiskott-Aldrich, aplastic anemia, Diamond-Blackfan Anemia, as well as inherited
metabolic diseases. In addition to focusing on determining the best use of stem cell
transplants for these disorders, I have also been involved in clinic
Donna Niedzwiecki
Professor of Biostatistics & Bioinformatics
Primary interests include clinical trials design and the design and analysis of biomarker
and imaging studies especially in the areas of GI cancer, lymphoma, melanoma, transplant
and cancer immunotherapy.
Kristin Marie Page
Assistant Professor of Pediatrics
Stem cell transplantation and/or cellular therapies can be used to treat a variety
of pediatric diseases including malignancies such as leukemia, lymphoma and myelodysplastic
syndrome in addition to certain non-malignant conditions (such as immune deficiencies,
inherited metabolic diseases, hemoglobinopathies, and bone marrow failure syndromes).
As the Director of the Pediatric Transplant and Cellular Therapy Survivorship Clinic,
my goal is optimize the care of survivors of pediatric stem cell t
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