Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.
Date
2021-05-12
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies, but is associated with significant morbidity and mortality. While deaths during the first year after transplant are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased GVHD, and lower relapse rates. OBJECTIVES: Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplant vs. matched related donor (MRD) and matched unrelated donor (MUD) transplant in patients with hematologic malignancies over a 20-year period. STUDY DESIGN: In this single center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant (ABMT) program from January 1, 1996 to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 post-HCT; received an allogeneic HCT for a disease other than a hematologic malignancy; or received cells from a haploidentical or mismatched adult donor. RESULTS: UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank p=0.03, Figure 1, median OS: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (HR: 0.69, 95% CI: 0.47-0.99, p=0.049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and non-relapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. CONCLUSIONS: UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex-vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.
Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Bohannon, Lauren, Helen Tang, Kristin Page, Yi Ren, Sin-Ho Jung, Alexandra Artica, Anne Britt, Prioty Islam, et al. (2021). Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies. Transplant Cell Ther. 10.1016/j.jtct.2021.05.002 Retrieved from https://hdl.handle.net/10161/23314.
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

Sin-Ho Jung
Design of Clinical Trials
Survival Analysis
Longitudinal Data Analysis
Clustered Data Analysis
ROC Curve Analysis
Design and Analysis of Microarray Studies
Big Data Analysis

Matthew Kelly
My research is broadly focused on elucidating the complex interactions that exist between the host microbiome and exogenous pathogens that cause infections in children. We have several ongoing projects evaluating: 1) the impact of the upper respiratory microbiome on the risk of colonization and invasion by bacterial respiratory pathogens among infants in Botswana; 2) associations between the gut microbiome of pediatric stem cell transplant recipients and the risk of infections (bloodstream infection, C. difficile infection) and graft-versus-host disease; and 3) the role of the gut and respiratory microbiomes in mediating COVID-19 infection susceptibility and disease severity in children. Ultimately, I aim to develop strategies that use targeted modification of the microbiome for the prevention of infections in children.

Taewoong Choi
Based on my prior experience in basic/translational immunology research and clinical hematopoietic stem cell transplantation, I am interested in early phase clinical protocols for novel immunotherapy of hematologic malignancies.

Gwynn Douglas Long
1. High dose therapy and autologous and allogeneic stem cell rescue for hematologic malignancies (especially multiple myeloma) and solid tumors.
2. Non-myeloablative allogeneic transplants for hematologic malignancies and solid tumors.
3. Supportive care for hematopoietic stem cell transplants.
4. Prevention and therapy of graft versus host disease.

Richard D Lopez

Stefanie Sarantopoulos

Nelson Jen An Chao
My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.
For more information see http://ed-media.mc.duke.edu/BMT.nsf

Mitchell Eric Horwitz
Allogeneic stem cell transplantation with a focus on the use of umbilical cord blood grafts; Allogenic stem cell transplantation for Sickle Cell Disease; Prevention of acute and chronic graft versus host disease; Improving immune recovery following alternative donor stem cell transplantation using donor graft manipulation.

Anthony D Sung
I am dedicated to the treatment of hematologic malignancies through cellular therapies such as hematopoietic stem cell transplantation (HCT). My research focuses on strategies to reduce complications of HCT and ranges from preclinical studies using murine models of HCT to Phase 1 and Phase 2 clinical trials. Areas of interest include the role of the microbiota (the trillions of bacteria living in and on our bodies), nutrition, and exercise in modulating HCT outcomes such as graft-versus-host disease (GVHD) and infections. In addition to advancing new pharmacological and cellular immunotherapies in support of these goals, we also are developing mobile health technologies (mHealth) to monitor patients at home, both as part of our innovative home transplant program as well as to improve follow up care of all our patients when they return home after transplant.
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.