A 70-year-old frail woman was evaluated for severe headaches and dizziness. Her previous therapy with imatinib and low-intensity chemotherapy for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph⁺ ALL) was truncated because of infections. Complete blood counts were normal (hemoglobin, 125 g/L; leukocytes, 4.43 × 10⁹/L, platelets, 219 × 10⁹/L), but examination of bone marrow (BM) and cerebrospinal fluid (CSF) revealed a relapse, with 2% lymphoblasts in the BM and 2800 cells per μL in CSF, including 93% lymphoblasts (panel A; May-Grünwald Giemsa stain, ×100 oil objective, total magnification ×1000). Those findings were corroborated by both flow cytometric and molecular analysis. Intrathecal treatment consisted of methotrexate, cytarabine, and methylprednisolone, every other day over a 2-week period. CSF clearance of the lymphoblasts and resolution of neurologic symptoms occurred after the first injection. Surprisingly, after 3 injections, the patient experienced mild headaches without fever or nuchal rigidity. CSF analysis showed 710 cells per μL, mostly neutrophils (panel B; May-Grünwald Giemsa stain, ×100 oil objective, total magnification ×1000) with normal CSF proteins (280 mg/L) and glucose (4.0 mmol/L). Infectious meningitis was ruled out after repeated microbiologic examinations of the CSF (direct examination, Gram stain, culture, multiplex polymerase chain reaction). Intrathecal chemotherapy was therefore implicated.

Cytarabine and methotrexate are commonly used for therapy, but they can occasionally cause drug-induced aseptic meningitis. The patient’s intrathecal chemotherapy was maintained. Symptomatic treatment was sufficient to manage the headaches, and CSF returned to normal in less than 2 weeks. Our observations illustrate a challenging diagnosis and the need to fully evaluate symptoms to prevent treating for the wrong diagnosis such as infection or therapy-resistant leukemia.