A 49-year-old woman was admitted to hospital with an elevated white blood cell (WBC) count and platelet count but without any other symptoms. The initial peripheral blood laboratory evaluation revealed a WBC count of 27,500 cells/microL (neutrophils 77.6%, lymphocytes 13.6%, monocytes 2.2%, eosinophils 1.9%, basophils 4.7%), hemoglobin of 12.7 g/dL, and platelet count of 174.9 x 104 cells/muL. No coagulopathy was observed. Bone marrow examination showed a total nucleated cell count of 43.5 x 104 cells/microL. Karyotype analysis revealed 46, XX, t(9;22)(q34;q11.2) in 20/20 cells, and fluorescence in situ hybridization of BCR/ABL was 98% positive. Sokal risk stratification was high.
The patient was diagnosed with CML in the chronic phase, and treatment with 100 mg dasatinib once daily was initiated.
Three months after the diagnosis, the patient achieved a complete cytogenetic response (CCyR), but complained of various indefinite symptoms in the interim. One week after starting dasatinib therapy, the patient complained of myodesopsia, although a physical examination and non-contrast computed tomography revealed no abnormalities. The myodesopsia persisted for 1 month and subsequently resolved. The patient then started to complain of headache, which was atypical and difficult to describe (the patient used expressions such as: 'I feel that metal is squished in my head', or, 'I feel a strange feeling like graveling'). Contrast magnetic resonance imaging (MRI) was performed, but revealed no abnormality. After these symptoms resolved, the patient began to complain of throat constriction and difficulty in swallowing. At the same time, she experienced edema in the face and extremities. We considered these symptoms to be adverse events of dasatinib, and discontinued the patient from dasatinib therapy at 1 year after the diagnosis of CML. At this point, the patient was in MR4 (real-time quantitative polymerase chain reaction [RT-PCR]; international scale, BCR-ABL IS), considered an optimal response under the European Leukemia Net criteria, and was switched to nilotinib 400 mg/day. The patient was still in MR4 at 18 months after diagnosis. From 12 months to 18 months after diagnosis, the patient again complained of various indefinite symptoms, such as heartburn, cough, and unexplained headache. All examinations to determine the cause of these symptoms were negative. Nineteen months after diagnosis, the patient experienced molecular failure, with an increase in IS from 0.0073% to 0.0163%. The patient was switched to 100 mg/day bostinib, and simultaneously complained of myodesopsia of the left eye. The symptom worsened and vision in both eyes gradually diminished until the patient was diagnosed with bilateral optic neuritis using contrast MRI (Fig. 1a). Steroid therapy and plasma exchange were initiated, but without a successful outcome.
Because the patient's bilateral optic neuritis was refractory to the treatment, we examined the cerebrospinal fluid (CSF) and found an increased WBC count (1636 cells/mm3), indicative of myeloid immature blasts (Fig. 1b). BCR-ABL mRNA levels in CSF were determined by RT-PCR and found to be 3.0 x 106 copy/mug RNA. The patient was therefore diagnosed as having CNS BC of CML. However, peripheral blood testing revealed no elevation of IS, bone marrow examination remained normal, and the patient remained in MR4. Thus, the patient was diagnosed with isolated CNS BC and was treated with intrathecal methotrexate, cytarabine, dexamethasone, and whole brain irradiation. Despite the MR4 stage of the patient, bostinib therapy was switched to 30 mg/day ponatinib, which is currently ongoing.