Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by presence of the Philadelphia (Ph) chromosome. CML has three distinguished phases: chronic, accelerated, and blastic. Approximately 90% of patients with CML are diagnosed in the chronic phase. Treatment with first (Imatinibe) or second (dasatinib and nilotinib) generation tyrosine kinase inhibitors (TKIs) usually leads to complete hematologic, cytogenetic, and molecular remissions. Extramedullary blast crisis (EBC) is a rare special kind of blast crisis of CML and usually accompanies systemic relapse. In extremely rare cases, the blast phase can affect the central nervous system without concomitant bone marrow involvement.

We report a case of a 34-year-old man who was diagnosed with CML twelve years back (2010) at our hospital. Due to irregular use and loss of response to imatinibe, he was on regular use of nilotinibe since 2017, achieving hematological, cytogenetic and molecular remission. The patient had a background of decompressive craniectomy following traumatic brain injury due to a motor vehicle crash in 2004. Between 2006-2017, he was affected by recurrent episodes of meningitis, both bacterial and viral, and a diagnosis of cerebrospinal fluid (CSF) fistula was made, but the patient refused corrective surgery. In April 2022, he presented to our emergency with acute visual loss. Brain imaging only showed the CSF fistula, but CSF cytogenetic presented 34% of myeloid blasts. At this point our patient was in complete hematologic and molecular response. Bone marrow revealed no morphological or cytogenetic evidence of relapse. The diagnosis of isolated CNS blast crisis was made. He was successfully treated with intrathecal chemotherapy and dasatinibe. The patient was then listed to Allogeneic hematopoietic stem cell transplantation, but no donor was found. A few months later, while maintaining cytogenetic and complete molecular remission, our patient presented to the emergency with seizures. Cerebrospinal fluid FISH analysis presented with Ph+ metaphases. Again, bone marrow analysis showed no morphological or cytogenetic evidence of relapse. He was over again successfully treated with intrathecal chemotherapy. In July 2023, the patient evolves with a hematological blastic crisis, Bone marrow analysis pointed 50% of myeloid blasts and a triple Ph+ complex karyotype, and he died due to a rapidly downhill course.

Here, we report an unusual case of CML that presented an extramedullary blast crisis. This case is unusual in 2 aspects: 1) The blast phase in the central nervous system without concomitant bone marrow involvement; 2) The recurrency in presence of an anatomical abnormality: The cerebrospinal fluid fistula. Despites CNS serves as the sanctuary site for CML, patients on long term TKIs therapy with haematological and cytogenetic remission rarely present with CNS blast crises. Isolated CNS blast crises are uncommon and limited to occasional case reports. The authors of this paper did not find any reports of the association between EBC and Traumatic CSF fistula.

This report brings attention to the importance of thinking of CNS involvement in the presence of neurological symptomatology in patients with CML, even in the chronic phase, and suggests the importance of a special attention to those patients with a potential blood–brain barrier abnormality.