Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning: The URTH Trial

• Type of Material: Article
• Authors: Shalini Shenoy, Washington University; Mark C. Walters, UCSF Benioff Children's Hospital; Alex Ngwube, Phoenix Children's Hospital; Sandeep Soni, Nationwide Children's Hospital; David Jacobsohn, Children's National Medical Center; Sonali Chaudhury, Northwestern University; Michael Grimley, Texas Transplant Institute; Kawah Chan, Texas Transplant Institute; Ann Haight, Emory University; Kimberly A. Kasow, University of North Carolina; Suhag Parikh, Duke University; Martin Andreansky, University of Miami; Jim Connelly, University of Michigan; David Delgado, Riley Children's Hospital; Kamar Godder, Nicklaus Children's Hospital; Gregory Hale, Johns Hopkins All Children's Hospital; Michael Nieder, Johns Hopkins All Children's Hospital; Michael A. Pulsipher, Children's Hospital Los Angeles; Felicia Trachtenberg, New England Research Institutes
• Language: English
• Date: 2018-06-01
• Publisher: ELSEVIER SCIENCE INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 The American Society for Blood and Marrow Transplantation
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2018.01.023
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• Volume: 24
• Issue: 6
• Start Page: 1216
• End Page: 1222
• Keywords: STANDARD; Hematology; REGIMEN; Unrelated donor; Thalassemia; Science & Technology; Immunology; HEMOGLOBINOPATHIES; STEM-CELL TRANSPLANTATION; Reduced-intensity conditioning; Hematopoietic stem cell transplant; Transplantation; EXPERIENCE; OUTCOMES; Life Sciences & Biomedicine; UMBILICAL-CORD BLOOD; BONE-MARROW-TRANSPLANTATION; NONMALIGNANT DISEASES; GRAFT
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI,.64% to.92%) and 79% (95% CI,.6% to.9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.