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Complete remission of central nervous system relapse with dasatinib 100mg/day in Philadelphia chromosome positive acute lymphoblastic leukemia

Authors
Jeong, Seong Hyun; Park, Joon Seong
Department
Department of Hematology-Oncology
Abstract
Central nervous system (CNS) relapse is a catastrophic event in acute lymphoblastic leukemia (ALL), especially more common in Philadelphia chromosome positive (ph+) ALL. In patients with ph+ ALL, overall response rate and survival are significantly improved by integration of imatinib as a front line therapy but imatinib has shown poor response to the CNS relapse. Here we report a ph+ ALL patient experienced complete remission (CR) of CNS relapse with dasatinb.

The patient is 24 male referred from private clinic due to many blasts in the peripheral blood. Bone marrow study revealed he had acute B lymphoblastic leukemia and also Philadelphia chromosome was positive. After one cycle of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) chemotherapy he achieved complete remission. One more cycle of hyper-CVAD and imatinib 400mg/day was given before he proceeded to allo-HSCT. HSCT was performed in molecular remission from matched related donor. He has maintained remission for 10 months since allo-HSCT. At eleven months after HSCT, the patient complained headache and serum BCR-ABL turned positive. Bone marrow study showed 99.6% donor chimerism without evidence of leukemic recurrence. Brain magnetic resonance imaging (MRI) showed prominent leptomeningeal enhancement and many leukemic blasts were detected in the central nervous fluid. Three times of intrathecal chemotherapy with methotrexate 12mg was given but blasts persisted in the CSF. Then the patient was started on dasatinb 100mg/day. Within one week of dasatinib treatment headache was improved and BCR-ABL returned negative within 1 month of dasatinib. The patient has been maintaining dasatinib for 8 months without recurrence and specific toxicity.

Dasatinib 100mg/day could achieve enough level to eradicate CNS leukemia. It may be due to better penetration to the CNS and high potency of inhibiting BCR-ABL. In ph+ ALL patients with CNS relapse, dasatinib should be the first choice of treatment.
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