Isolated central nervous system lymphoid blast crisis in chronic myeloid leukaemia in major molecular remission

Abstract

A 68-year-old man presented in August 2005 with bruising. The full blood count at that time showed haemoglobin 111 g/l, white blood cell (WBC) count 114 · 10/l (blast count 1AE2 · 10/l) and platelet count 125 · 10/l. Blood film and marrow examination were typical for chronic phase chronic myeloid leukaemia (Ph-positive). He was commenced on imatinib 400 mg/d and achieved complete cytogenetic remission within 6 months of diagnosis. In April 2007, the patient presented with leg cramps, progressive tremor, poor balance and headaches. There were no focal central nervous system (CNS) signs. Full blood count remained normal and computed topography and magnetic resonance imaging of brain and spine showed no abnormality. Examination of cerebrospinal fluid (CSF) obtained at lumbar puncture showed a raised WBC count (1540 · 10/l). CSF cytospin revealed medium to large sized blast cells with a background population of small, mature, lymphoid cells (top left). Flow cytometry using CD45/SSC (a measure of cytoplasmic granularity) confirmed two distinct lymphocyte populations (top right); a mature reactive T-cell population (red), with the larger, CD45 cells (blue) positive for terminal deoxynucleotidyl transferase, CD10, CD19, CD20 and CD34 (bottom) with surface immunoglobulin negative. CSF blast karyotype was 45–46, X,-Y, der(1)t(1;8)(q42;q11),i(9)(q10),t(9:22)(q34;q11), i(17)(q10)[cp20]. A diagnosis of lymphoid blast crisis was made. Repeat marrow examination was normal (including cytogenetics on 30 metaphases) and peripheral blood quantitative polymerase chain reaction for BCR-ABL1 was 0AE068% (i.e. ongoing major molecular remission). Treatment with intrathecal methotrexate 12AE5 mg and oral dexamethasone was commenced. CSF blasts cleared rapidly and clinical improvement was marked. Imatinib was stopped and dasatinib 50 mg bd commenced. Consolidation therapy with attenuated cranio-spinal irradiation is planned. Isolated lymphoid blast crisis presenting in CSF is very rare, with previous reports also describing concurrent marrow relapse. Our patient developed isolated CNS disease in the context of ongoing major molecular remission while on imatinib. The latter is known to penetrate poorly into the CNS. Dasatinib is thought to have better penetration, however marrow responses in blast phase disease, particularly those of lymphoid lineage, are not durable with this agent, hence the rationale for radiotherapy.