Blinatumomab-Related Lineage Switch of KMT2A/AFF1-Rearranged B-Lymphoblastic Leukemia to B/Myeloid Mixed-Phenotype Acute Leukemia and Myeloid Sarcoma Causing Spinal Cord Compression.
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Blinatumomab is a promising monoclonal antibody therapeutic for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). However, it has been associated with lineage switch in acute leukemia, particularly in cases of KMT2A-rearranged B-ALL, which carries a poor prognosis. While most lineage switch events present as acute myeloid leukemia (AML), rare cases may manifest as myeloid sarcoma. In the current report, we describe the development of myeloid sarcoma following blinatumomab treatment in a patient with refractory KMT2A-rearranged B-ALL. The patient, a 19-year-old African American male with primary Philadelphia chromosome-negative B-ALL, was initially treated with a pediatric-inspired chemotherapy regimen. He achieved pathologically morphologic remission after induction, but his minimal residual disease (MRD) testing remained persistently positive, eventually progressing to bone marrow relapse. The patient was then started on blinatumomab therapy, achieving a second morphological remission; however, his MRD remained detectable. During the fourth cycle of blinatumomab, the patient developed back pain and lower extremity weakness. Imaging revealed an extradural mass in the thoracic spine, resulting in spinal cord compression. Histopathologic evaluation of the mass confirmed a diagnosis of mixed-phenotype myeloid sarcoma harboring the same KMT2A rearrangement. Concurrent bone marrow biopsy revealed mixed-phenotype acute leukemia. The patient was subsequently lost to follow-up. This is the fourth reported case of myeloid sarcoma following blinatumomab therapy of persistent B-ALL. It highlights an unusual and serious pattern of relapse in an extramedullary site following blinatumomab therapy. Clinicians should remain vigilant for signs of lineage switch and extramedullary disease during treatment, particularly in patients with KMT2A-rearranged B-ALL, and consider imaging or biopsy when new neurologic or systemic symptoms arise.