Isolated central nervous system blast crisis in chronic myeloid leukemia

Abstract

Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is a rare event. Imatinib mesylate has become the treatment of choice, especially for patients for whom allogenic stem cell transplantation is not an option. Imatinib produces complete cytogenetic responses in excess of 80%. However, the penetration of the drug and its metabolites into the CNS (Central Nervous System) is poor. Hence for patients who are on prolonged imatinib therapy and continue to have complete cytogenetic responses, the central nervous system may become a sanctuary site. We report a patient who had a complete hematologic and cytogenetic response and presented with headache and vomiting. The MRI showed meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive for blasts. He was started on cranial radiotherapy and triple intrathecal chemotherapy. He showed good symptomatic improvement and cleared the blasts in the CSF. At the end of radiation, he was in complete hematological remission but had 50% marrow metaphases positive for Philadelphia chromosome. As he did not have a matched sibling donor, the dose of imatinib was increased to 600 mg daily. He continues to be in complete hematologic remission at the time of this report.

Central Nervous System Blast Crisis in Chronic Myeloid Leukemia on Imatinib Mesylate Therapy: Report of Two Cases

“…Though several case reports of CNS blast crisis in CML patients on Imatinib have been published from west [1,10,11], only limited Indian case reports are available [2,12]. On reviewing the literature it was found that in several studies [2,8,12], headache, vomiting were the common presenting features of CNS involvement and was seen in both our patients.…”

“…It has become the treatment of choice of CML in chronic phase especially for patients for whom allogenic stem cell transplantation is not an option [2,3]. It has also shown activity in CML patients in the accelerated phase or blast crisis [1].…”

“…This extramedullary blast crisis can involve lymph nodes, skin and soft tissues, serosal surfaces, bone, gastrointestinal and genitourinary tract. However CNS as a site of extramedullary blast crisis is rare [1,2].…”

“…It has emerged as the treatment of choice for Philadelphia positive CML patients in chronic phase and who are not candidates for allogenic hematopoetic stem cell transplantation [2,3]. It can induce haematological response in 95% of patients and major cytogenetic response in more than 60% of CML patients [1].…”

“…However the penetration of the drug and its active metabolites into the central nervous system (CNS) is poor [1][2][3]. Hence for patients who are on prolonged Imatinib therapy and continue to have complete haematologic and cytogenetic responses, the CNS may act as a sanctuary site [2,4].…”