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Published on: October 17, 2025
Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute
Kristin M Page1, Myriam Labopin2, Annalisa Ruggeri3
1Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.
Insights
Relapse after unrelated cord blood transplant (UCBT) for pediatric acute lymphoblastic leukemia (ALL) is reduced by graft-versus-host disease (GVHD) and total body irradiation (TBI). However, GVHD also increases nonrelapse mortality, necessitating balanced strategies.
Area of Science:
- Pediatric Hematology-Oncology
- Stem Cell Transplantation
- Leukemia Research
Background:
- Relapse remains a significant challenge in pediatric acute lymphoblastic leukemia (ALL) post-unrelated cord blood transplant (UCBT).
- UCBT offers a reduced graft-versus-host disease (GVHD) profile compared to other donor sources, yet relapse rates are comparable or lower.
Purpose of the Study:
- To identify risk factors associated with the 5-year cumulative incidence of relapse in pediatric ALL patients undergoing UCBT.
- To analyze the impact of various factors, including GVHD and conditioning regimens, on relapse risk and survival outcomes.
Main Methods:
- Retrospective analysis of 640 pediatric ALL patients (<18 years) in CR1 or CR2 receiving myeloablative conditioning and single-unit UCBT (2000-2012).
- Evaluation of conditioning agents (antithymocyte globulin, TBI) and HLA matching.
- Multivariate analysis (MVA) to determine significant predictors of relapse and survival.
Main Results:
- In CR1 patients, 5-year relapse incidence was 23%; acute GVHD (grades II-IV) and TBI were protective against relapse.
- In CR2 patients, 5-year relapse incidence was 28%; longer time to UCBT (≥30 months) and TBI were associated with decreased relapse risk.
- Fully HLA matched grafts were a risk factor for increased relapse, while acute GVHD showed a graft-versus-leukemia effect but increased nonrelapse mortality.
Conclusions:
- Graft-versus-host disease (GVHD) acts as a graft-versus-leukemia marker in pediatric ALL following UCBT.
- Total body irradiation (TBI) and avoiding fully HLA matched grafts may reduce relapse risk.
- Future strategies should aim to enhance graft-versus-leukemia effects while mitigating GVHD-related toxicities.
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.
