Discussion:
Although CML has become an indolent illness in the majority of patients, blast crises remain severe and often life-threatening complications, necessitating aggressive disease management and, when possible, preparation for allogeneic stem cell transplantation (allo-SCT). CNS involvement is not typical for CML, although it has been well described. Seeding of the CNS by leukemia cells is seen more often with high WBC counts at presentation [3]. Nevertheless, our patient continues in good condition without any signs of extramedullary disease relapse.
In cases of CNS blast crisis, patients often manifest clinical and radiological symptoms akin to those seen in meningitis or encephalitis. The cerebrospinal fluid (CSF) typically tests positive for myeloid or lymphoid blasts. In some instances, molecular testing of the CSF has even identified the characteristic BCR-ABL oncogene [8]. Our patient initially presented with left eye ptosis. While we didn’t confirm the presence of the BCR-ABL oncogene in the CSF, there was a substantial presence of myeloid blasts in the CSF, and the BCR-ABL oncogene was clearly detectable in the patient’s peripheral blood and bone marrow.
Our case patient presented with a remarkable clinical feature, specifically, left eye ptosis, without concurrent neurological symptoms, alongside a left-shifted moderate neutrophilic condition. Furthermore, the absence of an enlarged spleen made it less likely to consider a long-standing case of CML. This distinct clinical presentation presented a considerable diagnostic challenge. In such clinical scenarios, a comprehensive analysis of CSF to detect atypical cells or blasts is of paramount importance. This is because initiating appropriate therapy promptly can play a pivotal role in preventing lasting neurological deficits.
Traditional therapies for treating CNS involvement by Philadelphia-positive leukemia, such as radiotherapy, intrathecal chemotherapy, and high-dose systemic chemotherapy, have yielded unsatisfactory results with short-lived responses [17]. Managing such cases necessitates a well-considered choice of a tyrosine kinase inhibitor (TKI) with enhanced blood-brain barrier penetration, in addition to systemic and CNS-directed therapy. Dasatinib, a second-generation TKI, demonstrates a 325-fold greater potency in inhibiting the BCR-ABL oncogene in vitro compared to imatinib [18]. In our case, we opted for dasatinib over the first-generation TKI imatinib, as it has shown the ability to effectively penetrate the blood-brain barrier and provide sustained responses in CNS Philadelphia-positive leukemias [19]. There is an urgent need for novel strategies to treat such complicated cases, perhaps by incorporating therapies used for primary CNS cancer, such as high-dose methotrexate or temozolomide. Dasatinib may have an important role in managing CNS CML blast crises, especially when combined with whole brain radiation therapy.