A Case of Isolated Lymphoblastic Relapse of the Central Nervous System in a Patient with Chronic Myelogenous Leukemia Treated with Imatinib

Isolated central nervous system (CNS) relapse is a rare, unpredictable event in patients with CML. Some studies have reported cases of isolated CNS relapse in CML [1-13]. However, very few studies have reported on isolated CNS relapse in the blast phase (BP) of CML in Korea [14, 15]. We report a case of BP CML with extramedullary lymphoblast proliferation in the CNS without evidence of disease in the peripheral blood (PB) and bone marrow (BM). A 54-yr-old man was diagnosed as having BCR/ABL1 (b2a2 type)-positive CML in July 2012. He was considered to be in the chronic phase on the basis of his blast count on PB smear and BM aspiration, and subsequently, he was administered imatinib (400 mg/day). Three months after diagnosis, he demonstrated a complete hematologic response, major cytogenetic response, and no major molecular response according to the National Comprehensive Cancer Network Guidelines in Oncology for CML (karyotype 46,XY,t(9;22)(q34;q11.2)[7]/46,XY[23], BCRABL1 fusion transcript of 0.933% based on the International Scale [IS]) [16]. Seven months after initial diagnosis, he was readmitted with a complaint of headache since two months. Diffusion brain magnetic resonance imaging with magnetic resonance angiography revealed abnormal leptomeningeal enhancement of both paramedian gyri, suggesting involvement of leukemic cells. In cerebrospinal fluid (CSF) study, his CSF was turbid and had increased number of white blood cells (WBCs) (3.5×10/L), and almost all WBCs were lymphoid cells. Wright stain of cytospin-smeared CSF showed lymphoid cells with high nuclear-to-cytoplasmic ratio and coarse chromatin pattern with prominent nucleoli. Lymphoid cells were negative on periodic acid-Schiff staining. In flow cytometric analysis, the lymphoid cells had an early pre-B phenotype with an aberrant CD33 expression (positive for CD45, CD34, CD33, terminal deoxynucleotidyl transferase (TDT), HLA-DR, CD19, and CD10). The result of reverse transcriptase-PCR for detecting BCR-ABL1 fusion transcript was positive (b2a2 type) in CSF. On complete blood count analysis, Hb level was 13.3 g/dL, WBC count was 11.41× 10/L, and platelet count was 167×10/L. There was no morphologic evidence of lymphoblasts in PB and BM samples (Fig. 1). The patient was treated with dasatinib, intrathecal methotrexate, and cranial irradiation therapy. One week after initiation of treatment, CSF showed decreased WBCs (0.002×10/L) with no evident malignant cells. Two months after relapse, patient demonstrated a complete hematologic response, complete cytogenetic response, and major molecular response (karyotype