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.