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Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.

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Date
2017-08
Authors
Page, Kristin M
Labopin, Myriam
Ruggeri, Annalisa
Michel, Gerard
Diaz de Heredia, Cristina
O'Brien, Tracey
Picardi, Alessandra
Ayas, Mouhab
Bittencourt, Henrique
Vora, Ajay J
Troy, Jesse
Bonfim, Carmen
Volt, Fernanda
Gluckman, Eliane
Bader, Peter
Kurtzberg, Joanne
Rocha, Vanderson
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(17 total)
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Abstract
For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n = 383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000 to 2012. Most received antithymocyte globulin (88%) or total body irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1 (50%) or 2<sup>+</sup> (34%) HLA loci. Considering patients in CR1, the rates of 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated.
Type
Journal article
Subject
Humans
Recurrence
Disease-Free Survival
Transplantation Conditioning
Cord Blood Stem Cell Transplantation
Survival Rate
Risk Factors
Time Factors
Adolescent
Child
Child, Preschool
Infant
Female
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Unrelated Donors
Allografts
Permalink
https://hdl.handle.net/10161/24590
Published Version (Please cite this version)
10.1016/j.bbmt.2017.04.015
Publication Info
Page, Kristin M; Labopin, Myriam; Ruggeri, Annalisa; Michel, Gerard; Diaz de Heredia, Cristina; O'Brien, Tracey; ... Rocha, Vanderson (2017). Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 23(8). pp. 1350-1358. 10.1016/j.bbmt.2017.04.015. Retrieved from https://hdl.handle.net/10161/24590.
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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Scholars@Duke

Kurtzberg

Joanne Kurtzberg

Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg conducts both clinical and laboratory-based translational research efforts, all involving various aspects of normal and malignant hematopoiesis. In the laboratory, her early work focused on studies determining the mechanisms that regulate the choice between the various pathways of differentiation available to the pluripotent hematopoietic stem cell. Her laboratory established a CD7+ cell line, DU.528, capable of multilineage differentiation as well as self-renewal, and subse
Page

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
Troy

Jesse David Troy

Assistant Professor of Biostatistics & Bioinformatics
I am a biostatistician supporting research in cell therapies and regenerative medicine at the Duke Marcus Center for Cellular Cures, and research studies in cancer therapeutics and palliative care at the Duke Cancer Institute. I also teach biostatistics in the Master of Biostatistics program and the <a href="
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