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The Outcome of Allogeneic Hematopoietic Cell Transplantation for Children with FLT3/ITD-Positive Acute Myelogenous Leukemia

Tal Schechter, Adam Gassas, Heidi Chen, Jessica Pollard, Soheil Meshinchi, Irina Zaidman, Johann Hitzler, Mohamed Abdelhaleem, Richard Ho, Jennifer Domm, Ann Woolfrey, Haydar Frangoul

Biology of Blood and Marrow Transplantation, In Press, Accepted Manuscript, Available online 16 August 2014

Abstract

FLT3 internal tandem duplication (FLT3/ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome is reported. We determined the outcome of 29 children with FLT3/ITD positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in four pediatric centers. Eleven patients (38%) received matched-related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplant related mortality (TRM). Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% CI 20.4-54.9%). 2-years DFS and OS were 65.3% (95% CI 45.1-79.6%) and 82.2% (95% CI 58.5-91.3%), respectively. There was no difference between the DFS of patients who received related donors versus alternative donors, (HR 2.64 (0.79-8.76), p=0.1) using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR 1.42 (1.04-1.93), p=0.03). The use of TBI in the preparative regimen was associated with superior DFS and OS (HR 0.29 (0.08-0.99), p =0.04) (HR 0.07 (0.01-0.62), p= 0.002), respectively. We conclude that allogeneic HSCT improve DFS and OS in children with FLT3/ITD positive AML compared to what has been reported in those treated with chemotherapy alone.


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