Flt3 is a receptor tyrosine kinase involved in the survival of hematopoietic stem cells and activating mutations of Flt3 were reported to have prognostic significance in AML. This is the first study analyzed the Flt3 mutations in pediatric non-promyelocytic AML patients received same treatment scheme. Total 61 patients received BH-AC, idarubicin, 6-TG, and intrathecal Ara-C as an induction therapy. Once in complete remission (CR), patients with a matched related donor received BMT after two courses of consolidation therapy while those without donor received autologous peripheral blood stem cell transplantation with BCNU, etoposide, Ara-C, and cyclophosphamide conditioning regimen after four courses of consolidation therapy. Flt3 internal tandem duplication (Flt3/ITD) of juxtamembrane domain and D835 mutation (Flt3/D835) of tyrosine kinase domain were analyzed with PCR of genomic DNA. The incidence of Flt/ITD and Flt D835 were 6.6% (4/61) and 3.3% (2/61), respectively. After induction therapy, the CR was archived in 93.4% of the patients and all six patients with Flt3 mutations archived CR. The overall survival and event free survival of all patients were 58.8% and 45.6%, respectively. The disease free survival (DFS) was same as the relapse free survival (48.9%) because all events after CR were relapse. The patients with Flt3/D835 are still alive after autologous peripheral blood stem cell transplantation. The DFS of patients with Flt3/ITD (0%) was lower than that of others (51.9%) significantly (P = 0.0062). Flt3/ITD was the sole adverse prognostic factor for DFS in multivariate analysis (RR=5.6). The patients with Flt3/ITD relapsed very early even after receiving bone marrow transplantation from matched related donor with little BuCy conditioning. New therapeutic scheme such as stem cell transplantation with very intensive conditioning just after complete remission could be applied in pediatric non-promyelocytic AML patients with Flt3/ITD mutation.

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Topics:
flt3 gene, leukemia, myelocytic, acute, ms-like tyrosine kinase 3, mutation, pediatrics, impedance threshold device, complete remission, consolidation therapy, cytarabine, neoadjuvant therapy

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2005, The American Society of Hematology
2004
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