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Published on: October 31, 2012
Graft-versus-leukaemia effect in children: chronic GVHD has a significant impact on relapse and survival
A Gustafsson Jernberg1, M Remberger, O Ringdén
1Department of Paediatrics, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden.
Insights
Chronic graft-versus-host-disease (GVHD) after stem cell transplantation (SCT) in children with leukaemia is linked to a graft-versus-leukaemia (GVL) effect. This effect improves survival by reducing relapse risk.
Area of Science:
- Hematology
- Pediatric Oncology
- Immunology
Background:
- Allogeneic stem cell transplantation (SCT) is a curative option for childhood leukaemia.
- Graft-versus-host-disease (GVHD) is a common complication of SCT.
- The potential graft-versus-leukaemia (GVL) effect, distinct from GVHD, is crucial for long-term outcomes.
Purpose of the Study:
- To investigate the association between chronic GVHD and the GVL effect in pediatric acute leukaemia.
- To determine if GVHD influences relapse rates and survival post-SCT.
- To analyze the independent predictive value of GVHD on treatment outcomes.
Main Methods:
- Retrospective evaluation of 169 children with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) undergoing SCT.
- Analysis of chronic and acute GVHD incidence, relapse rates, and survival probabilities.
- Cox regression modeling to assess independent predictors of outcomes.
Main Results:
- The 5-year cumulative incidence of chronic GVHD was 34%.
- Patients with chronic GVHD showed a significantly lower relapse rate (30% vs. 45%) and improved 5-year survival (77% vs. 51%).
- Chronic GVHD was an independent predictor of decreased relapse risk and increased survival, particularly in late-stage disease and ALL.
Conclusions:
- The study supports a GVL effect mediated by chronic GVHD in childhood leukaemia.
- Chronic GVHD is associated with reduced leukaemia relapse and enhanced survival after SCT.
- Acute GVHD did not demonstrate an independent predictive role in this cohort.
Abstract:
To examine whether graft-versus-host-disease (GVHD) is associated with a graft-versus-leukaemia (GVL) effect that also influences the outcome of allogeneic stem cell transplantation (SCT) in childhood acute leukaemia, we evaluated all consecutive (n=169) children who had undergone SCT for ALL and AML at our centre. Median follow-up was 7 years. The 5-year probability of chronic GVHD was 34%. Median time to relapse was 24 months in children with chronic GVHD and 6 months in those without. The corresponding 5-year probabilities of relapse were 30 and 45% (P=0.01). The 5-year probability of survival was 54%. Patients with chronic GVHD had a significantly better survival, 77 vs 51% (P=0.01). In a Cox regression model, chronic GVHD independently decreased the risk of relapse (RR 0.44) and further predicted an increased chance of relapse-free survival (RR 1.7) and survival (RR 2.6). The impact of chronic GVHD on survival was most apparent in late-stage disease and in ALL. Acute GVHD was not an independent predictor for relapse or death in this study. This study is in support of a GVL effect in childhood leukaemia related to chronic GVHD, reducing the risk of relapse and improving survival.
