title: Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutation status.
abstract: Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph(+)MPAL) is a rare type of acute leukemia having myeloid and lymphoid features. In the present study, we describe the successful treatment of a 71-year-old Japanese female patient with Ph(+)MPAL by the alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutations. The patient survived in her third complete remission (CR) for over 4 years. In her first CR, the patient was treated with multiple-agent chemotherapy and underwent maintenance therapy with imatinib and monthly vincristine and prednisolone (VP). At the first relapse, an examination of the bone marrow revealed a transformation into acute lymphoblastic leukemia and an F317L mutation in BCR-ABL1 gene, which responded preferentially to nilotinib over dasatinib. She achieved second CR, and nilotinib with VP therapy was selected for maintenance treatment. At second relapse, BCR-ABL1 mutational analysis revealed Y253H mutation instead of F317L mutation, resulting in resistance to nilotinib. The patient achieved third CR with dasatinib and VP therapy, and maintained CR with this treatment. This suggests that appropriate alternation of TKIs may contribute to long-term survival in elderly patients with Ph(+)MPAL.
authors.affiliation: Department of Hematology, Oami Municipal Hospital, 884-1 Tomita, Oamishirasato-shi, Chiba, 299-3221, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kawajiri
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shio
authors.initials: S
authors.lastname: Sakai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Chikako
authors.initials: C
authors.lastname: Ohwada
authors.forename: Emiko
authors.initials: E
authors.lastname: Sakaida
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
mesh_terms: D000208:Acute Disease; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl