Effectiveness of combined therapy with midostaurin and standard chemotherapy and high dose chemotherapy with allogeneic stem cell transplantation in high risk acute myeloid leukemia with FLT3-TKD and NPM1 mutations

Abstract

Many genetic disorders occur in patients suffering from acute myeloid leukaemia (AML). The most common mutations found in such patients are in the nucleophosmin (NPM) gene and the FLT3 tyrosine kinase receptor gene. NPM1 mutation is observed in over half of AML patients, showing a favourable prognosis, however FLT3 mutations worsen the course of leukaemia and treatment outcomes; ie. when internal tandem duplication (ITD) and point mutations occur in the tyrosine kinase (TKD) domain. Deploying FLT3 tyrosine kinase inhibitors thus offers a prospect for improving treatment and prolonging the survival of patients with AML, burdened with the FLT3 gene mutation. Midostaurin and gilteritinib are first type FLT3 inhibitors which are used to treat patients with AML FLT3-TKD due to their mechanism of action. This paper presents the case of a 30-year-old AML patient diagnosed with NPM1 and FLT3-TKD mutations, reticulin bone marrow fibrosis and extramedullary sites of AML. Treatment was individualised and induction chemotherapy was combined with midostaurin. After first-line treatment with midostaurin, complete remission was achieved, as confirmed by histopathological examination of the bone marrow. Subsequently, two cycles of consolidation chemotherapy were given and allogeneic haematopoietic stem cells were transplanted from an unrelated donor after myeloablative conditioning. The patient has remained in complete leukaemia remission, 22 months after diagnosis.