Key Word:
Central Nervous System, Chronic Myeloid Leukemia, Blast Crisis, Tyrosine Kinase Inhibiter
Abbreviations :
CNS: Central nervous system
CML: Chronic myeloid leukemia
CP: Chronic phase
TKI: Tyrosine kinase inhibitor
CSF: Cerebrospinal fluid
Introduction :
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder involving increased proliferation of the granulocytes without loss of differentiation capacity. It is defined by the presence of the Philadelphia chromosome, which results from a reciprocal translocation between chromosomes 9 and 22, specifically t(9;22)(q34:q11). this translocation leads to the fusion of the break point cluster region (BCR) with the ABL gene, which forms an oncogene, the transcript of which is an oncoprotein with a tyrosine kinase function [1]. CML is most frequently diagnosed in the chronic phase (CP) although it can less commonly present as an accelerated crisis or even progress to an acute leukemia, known as a blast crisis. Approximately 80% of blast crises manifest as acute myeloid leukemia, with the remaining cases being acute lymphoblastic leukemia. Treatment with the first-generation tyrosine kinase inhibitor (TKI), imatinib, achieves complete hematologic, cytogenetic, and molecular remissions in approximately 90%, 70%, and 30% of patients, respectively [2,3]. In rare instances, extramedullary involvement may occur, such as the presence of soft tissue leukemic infiltrates in various sites, which can be termed chloroma, myeloblastoma, or myeloid sarcoma [2–4, 7–10]. CML patients rarely present with a CNS blast crisis, which is typically reported in patients undergoing imatinib treatment [7–14]. The occurrence of CNS blast crisis is likely attributed to the limited penetration of the drug through the blood-brain barrier, making the CNS a sanctuary site [15,16]. This report describe an extramedullary rare case of 43-year-old male with CML who experienced an extramedullary blast crisis in the central nervous system. Treatment options and monitoring of disease response are discussed.
Case report :
We present the case of a 43-year-old male who was diagnosed with CML six years ago and had been undergoing treatment with imatinib 400 mg once daily. He presented with symptoms of headache and left eye ptosis, as figure (1), without exhibiting any other neurological or systemic manifestations. On physical examination, he appeared as a generally healthy young male with a normal-sized spleen and stable vital signs.
Upon initial assessment, his laboratory tests indicated normal levels of electrolytes, liver and kidney function, but high lactate dehydrogenase level of 896 U/l. His complete blood counts revealed a hemoglobin level of 9.1 g/dl, a white blood cell count of 40,000 × 10^9/l, and a platelet count of 120 × 10^9/l, with a peripheral blood smear showed left shifted neutropilic with 4% myeloid blasts.
Subsequent bone marrow aspiration and biopsy confirmed an accelerated-phase CML diagnosis. BCR-ABL oncogene analysis by polymerase chain reaction yielded a positive result of 0.36%. Brain CT scans revealed multiple lesions around the cerebral ventricular area, as figure (2).
Due to the absence of a prior history and due to his CNS symptoms and signs, treatment switched to dasatinib 100 mg once daily. Unfortunately, after a period of two months, the neurological symptoms worsened. Subsequently, the patient underwent intrathecal of the cerebrospinal fluid, which was found to contain cloudy yellowish cerebrospinal fluid (CSF) with atypical/blast CML cells, confirming the presence of CNS extramedullary myeloid blast infiltration, as figure (3). Furthermore, flow cytometry analysis of the bone marrow aspiration supported a diagnosis of blast-phase CML with immunophenotyping positive for CD 13, CD 33, CD 34, CD 117, MPO, HLA-DR. Analysis of the BCR-ABL oncogene through PCR revealed a elevated in positive result of 1.22%.
Treatment for the patient was adjusted to continue dasatinib at a daily oral dose of 100 mg. Additionally, an induction therapy (7 + 3) was initiated, consisting of Cytarabine 100 mg/m2 and doxorubicin 45 mg/m2, along with 7 doses of intrathecal methotrexate/ Cytarabine/ dexamethasone. Unfortunately, the patient experienced prolonged pancytopenia and multiple infections, which were compounded by the patient’s overall poor general condition. The patient has continued to receive dasatinib 100 mg orally daily, being followed by 3 monthly PCR for BCR-ABL oncogene from peripheral blood and annual fluorescence in situ hybridization test from BM aspirate. He remains in complete cytogenetic and molecular remission with no current evidence of active extramedullary disease 3 months prior to writing this report.