Liposomal Cytarabine (DepoCyte) for Treatment of Myeloid CNS Relapse in CML Occurring during Therapy with Imatinib.

Abstract

Central nervous system (CNS) relapse in chronic myeloid leukemia (CML) is rare and if recorded is usually found to occur in patients with lymphoblastic transformation or in those with a generalized myeloid relapse. The BCR/ABL tyrosine kinase (TK) inhibitor imatinib is highly effective in patients with CML, but hardly crosses the blood-brain-barrier. We report on two CML patients who developed a myeloid CNS relapse during treatment with imatinib. One patient was in major cytogenetic response at the time of CNS relapse. In both cases, the myeloid origin of neoplastic cells in the cerebrospinal fluid (CSF) was demonstrable by immunophenotyping, and their leukemic origin by detection of the BCR/ABL oncoprotein. No BCR/ABL kinase domain mutations could be detected. Both patients received intrathecal liposomal cytarabine (DepoCyte®) (50 mg each cycle; 6 cycles). In one patient, additional CNS radiation was performed, whereas in the other patient, consecutive treatment with dasatinib (70 mg per os twice daily) was started. In response to therapy, the clinical symptoms resolved and the leukemic cells in the CSF disappeared in both patients. After four months of observation, both patients are in complete cytogenetic and major molecular response, without evidence for a systemic or a CNS relapse. In conclusion, ‘anatomic' resistance against imatinib in the CNS can lead to an (isolated) myeloid CNS relapse. Liposomal cytarabine with or without radiation is effective as local therapy in these patients. For treatment of patients with a systemic relapse involving the CNS and for prophylaxis, second-generation BCR/ABL TK inhibitors crossing the blood-brain-barrier such as dasatinib should be considered.