title: Efficacy of Dasatinib in a CML Patient in Blast Crisis with F317L Mutation: A Case Report and Literature Review.
abstract: The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has significantly increased survival rate and quality of life for patients with CML. Despite the high efficacy of imatinib, not all patients benefit from this treatment. Resistance to imatinib can develop from a number of mechanisms. One of the main reasons for treatment failure is a mutation in the BCR-ABL gene, which leads to therapy resistance and clonal evolution. Clearly, new treatment approaches are required for patients who are resistant to imatinib. However, mutated clones are usually susceptible to second-generation TKIs, such as nilotinib and dasatinib. The choice of the therapy depends on the type of mutation. A large trial program showed that dasatinib is effective in patients previously exposed to imatinib. However, for a minority of patients who experience treatment failure with TKI or progress to advanced-phase disease, allogeneic stem cell transplantation (allo-SCT) remains the therapeutic option. In spite of the high curative potential of allo-SCT, its high relapse rate still requires a feasible strategy of posttransplant treatment and prophylaxis. We report a case of a CML patient with primary resistance to first-line TKI therapy. The patient developed an undifferentiated blast crisis. Before dasatinib therapy, the patient was found to have an F317L mutation. He was successfully treated with dasatinib followed by allo-SCT. In the posttransplant period, preemptive dasatinib treatment was used to prevent disease relapse.
authors.affiliation: R.M. Gorbacheva Memorial Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, St Petersburg, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Morozova
authors.affiliation: R.M. Gorbacheva Memorial Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, St Petersburg, Russia.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Vlasova
authors.affiliation: R.M. Gorbacheva Memorial Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, St Petersburg, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Pryanishnikova
authors.affiliation: R.M. Gorbacheva Memorial Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, St Petersburg, Russia.
authors.forename: K V
authors.initials: KV
authors.lastname: Lepik
authors.affiliation: R.M. Gorbacheva Memorial Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, St Petersburg, Russia.
authors.forename: B V
authors.initials: BV
authors.lastname: Afanasyev
keywords: BCR-ABL mutations; CML; F317L mutation; TKI; allo-SCT; dasatinib