Hematopoietic cell transplant compared with standard care in adolescents and young adults with sickle cell disease.
Date
2025-03
Journal Title
Journal ISSN
Volume Title
Citation Stats
Attention Stats
Abstract
Abstract
Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives were a comparison of the changes in SCD-related events, functional outcomes, and organ function. The data were analyzed according to the intent-to-treat principle. A total of 113 participants were enrolled with 28 in the donor arm and 85 in the no donor arm. The 2-year probabilities of survival were 89% and 93%, in the donor vs no donor arms. Vaso-occlusive pain (VOC) was less frequent in the donor arm in the second year after biologic assignment (P < .001). Based on PROMIS-57 surveys, there was a decrease in fatigue (P = .003) and an increase in the ability to participate in social roles and activities (P = .003) in the donor arm 2 years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the donor arm led to improvements in VOC, fatigue, and social function. This trial was registered at www.clinicaltrials.gov as #NCT02766465.Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Walters, Mark C, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K Waller, John E Levine, John J Strouse, Joseph H Antin, et al. (2025). Hematopoietic cell transplant compared with standard care in adolescents and young adults with sickle cell disease. Blood advances, 9(5). pp. 955–965. 10.1182/bloodadvances.2024013926 Retrieved from https://hdl.handle.net/10161/34201.
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.
Collections
Scholars@Duke
John J. Strouse
My research has focused on the epidemiology, risk factors, and prevention of the pulmonary and central nervous system complications of sickle cell disease and includes retrospective and prospective cohort studies and clinical trials. I received my Ph.D. in clinical investigation from the Johns Hopkins Bloomberg School of Public Health for a series of studies to identify predictors of cognitive function in children with sickle cell disease. This work has expanded to the evaluation of the interaction between environment and disease in both children and adults and the functional evaluation of adults with sickle cell disease. My other research interests include the application of large clinical, research, and administrative databases to the study of rare hematological diseases and interventions to improve quality of and access to care for sickle cell disease. I serve on the American Society of Hematology Sickle Cell Taskforce and Sickle Cell Pain Guideline Panel and am co-chair of the American Society of Hematology Healthcare Professional Education and Training Work Group.
Jennifer Jaroscak
Keith Michael Sullivan
Research areas
- Late effects of cancer treatment and stem cell transplantation
- Chronic graft-versus-host disease
- Transplantation for sickle cell and autoimmune diseases
- Knowledge engineering
Early on, Dr. Sullivan and the team at Fred Hutchinson Cancer Research Center developed a systematic investigative approach for the diagnosis and treatment of chronic graft-versus-host disease (GVHD), the major cause of late morbidity and non-relapse mortality following allogeneic stem cell transplantation (SCT). As a result of this work, it became clear that blood and marrow transplant recipients require systematic long-term follow-up to evaluate and treat late complications of high-dose chemoradiotherapy and SCT.
The program grew into a large multidisciplinary team, resulting in improvement in patient outcome and quality of life. Through the late events project, he also contributed to outcomes research, computer decision support systems, and knowledge engineering for follow-up care. With quality of life as a focus, research pursued the application of SCT to diseases with high morbidity but little immediate mortality. For young patients with advanced, symptomatic sickle cell disease, myeloablative conditioning and SCT from an HLA-identical sibling has led to an 86% long-term survival free of sickle cell disease. For individuals with autoimmune diseases such as multiple sclerosis, scleroderma, and systemic lupus erythematosus, current therapy is often incomplete and significant morbidity from the disease or its treatment is observed.
Recent preclinical and clinical data suggest that high-dose immunosupression and SCT can halt the progression and, in some settings, reverse the course of autoimmune diseases. Since his arrival at Duke University, over 30 centers nationwide are participating in Duke-led phase II and III trials to test the toxicity, efficacy, and quality of life following autologous and allogeneic stem cell transplantation for autoimmune diseases.
These trials will also serve as platforms to study the immune repertoire and mechanistic pathways before and after SCT to gain greater insight into the basic mechanisms of autoimmunity.
A national repository of tissue and cell specimens is also part of these NIH-supported trials to further promote scientific study from these unique patients.
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.