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

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+ (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

Department

Description

Provenance

Subjects

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

Citation

Published Version (Please cite this version)

10.1016/j.bbmt.2017.04.015

Publication Info

Page, Kristin M, Myriam Labopin, Annalisa Ruggeri, Gerard Michel, Cristina Diaz de Heredia, Tracey O'Brien, Alessandra Picardi, Mouhab Ayas, et al. (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.

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Scholars@Duke

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 transplantation, cellular therapies and chemotherapy. To further support this goal, my research interests include improving patient-reported health related quality of life, access to survivorship care, and further understanding the pathophysiology of certain late effects with the ultimate goal of identifying treatments.


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