Abstract
We previously showed that minimal residual disease (MRD) detection pre-hematopoietic cell transplant (HCT) and acute GvHD (aGvHD) independently predicted risk of relapse in pediatric ALL. In this study we further define risk by assessing timing of relapse and the effects of leukemia risk category and post-HCT MRD. By multivariate analysis, pre-HCT MRD <0.1% and aGvHD by day +55 were associated with decreased relapse and improved event-free survival (EFS). Intermediate leukemia risk status predicted decreased relapse, and improved EFS and overall survival (OS). Patients with pre-HCT MRD ⩾0.1% who did not develop aGvHD compared with those with MRD <0.1% who did develop aGvHD had much worse survival (2 years EFS 18% vs 71%; P=0.001, 2 years OS 46 vs 74%; P=0.04). Patients with pre-HCT MRD <0.1% who did not experience aGvHD had higher rates of relapse than those who did develop aGvHD (40% vs 13%; P= 0.008). Post-HCT MRD led to a substantial increase in relapse risk (HR=4.5, P<0.01). Patients at high risk of relapse can be defined after transplant using leukemia risk category, presence of MRD pre or post HCT, and occurrence of aGvHD. An optimal window to initiate intervention to prevent relapse occurs between day +55 and +200 after HCT.
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Acknowledgements
This study was supported in part by N01 HC-45220/HHSN268200425220C, U10 CA098543 and R01CA1116660. PBMTC activities were supported by 2U01HL069254 and a consortium grant from the St Baldrick’s Foundation.
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This study was presented in part at the American Society of Hematology Meeting, December 2012 and the Second International Workshop: Biology Prevention and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation, November 5–6, 2012, Bethesda MD, Plenary Oral Presentation, Best Abstracts Session.
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Pulsipher, M., Langholz, B., Wall, D. et al. Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested?. Bone Marrow Transplant 50, 1173–1179 (2015). https://doi.org/10.1038/bmt.2015.103
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DOI: https://doi.org/10.1038/bmt.2015.103
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