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).

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.bbmt.2013.11.021

Publication Info

Parikh, Suhag H, Adam Mendizabal, Cara L Benjamin, Krishna V Komanduri, Jeyaraj Antony, Aleksandra Petrovic, Gregory Hale, Timothy A Driscoll, et al. (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.

Scholars@Duke

Driscoll

Timothy Alan Driscoll

Associate 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.

Martin

Paul Langlie Martin

Professor Emeritus 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 clinical research investigating the prevention and treatment of transplant related morbidity, particularly veno-occlusive disease of the liver, infections and diffuse alveolar hemorrhage. As study chair for the Children's Oncology Group protocol 9904, I was involved in the development, implementation and analysis of a large, international frontline study of childhood acute lymphoblastic leukemia. Results from this study show that a significant number of children with certain favorable cytogenetic abnormalities in their leukemic cells and who have a rapid response to their initial chemotherapy can expect to have a >95% chance of cure when treated with relatively low intensity chemotherapy.  

I have concentrated on providing high quality care for high risk leukemia patients who require high intensity therapies, such as stem cell transplant and immunotherapy.  As a member of the Pediatric Transplant and Cellular Therapy Division I provide clinical care for these patients.  As a member of various cooperative groups and local PI for several drug trials, I have worked to provide better care and more specific therapies for the toxicities associated with stem cell transplant.  

I have also collaborated with the Pediatric Immunology Division to provide a life-saving therapy for a small group of patients with thymic dysfunction, which causes severe immunodeficiency.  Our clinical team now provides support during these patients hospital admissions for donor thymus tissue implantation.  We once again achieved a new record for the number of implanted patients during the 2022-2023 academic year.

Niedzwiecki

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.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.