PMC10151792_01
Clinical data of case 1. (A) Flow cytometry analysis of cerebral spinal fluid (CSF) before and after blinatumomab (blina). (B) G banded chromosome analysis before and after blina. (C) Sanger sequencing of ABL1 kinase domain before and after blina. (D) Fluorescence in situ hybridization (FISH) analysis of BCR::ABL1 fusion before and after blina. (E) Timeline of treatments and responses of case 1. VP, vincristine 1.5 mg/m2 intravenously, per week for 4 times and prednisolone 1 mg/kg, once daily, for 4 weeks; HD-MTX, MTX 3.5 g/m2, intravenously, for one day.
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Blasts from the CSF were CD19 positive as detected by FCM and were positive for BCR::ABL1 fusion by FISH ( Figures 1A, D ). BM ( Figures 1B, C ). Blinatumomab (9 microg d1-7, 28 microg d8-28) was administered combined with olverembatinib (40 mg, every other day). The treatment process of case 1 is depicted in  Figure 1E .
PMC10151792_02
Clinical data of case 2. (A) Schematic diagram of the MEF2D::BCL9 fusion before and after blina. (B) Flow cytometry analysis of CSF before and after blina. (C, D) Brain MRI analysis before and after blina. (E) Timeline of treatments and responses of case 2. VDLP, vincristine, daunorubicin, L-asparaginase and prednisone; VICP, cyclophosphamide (750 mg/m2), idarubicin 10 mg per week for 4 times, vincristine 1.5 mg/m2 per week for 4 times, prednisone 60 mg/m2, once daily, 4 weeks; MA, methotrexate 1 g/m2, intravenously, d1, Ara-c 3 g/m2, intravenously, q12h d2-3; MCAV, Mitoxantrone liposomes 40 mg combined with CAV regimen (cladribine 5 mg/m2, d2-6, cytarabine 20 mg q12h, d2-8 and dose-escalation of venetoclax d1-7); Blina, Blinatumomab (9 microg d1-7, 28 microg d8-28); CNSL, central nervous system leukemia.
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MEF2D::BCL9 fusion gene was detected by RNA sequencing ( Figure 2A ). CSF, which were CD19 positive ( Figure 2B ). CNSL (CNS-3) was confirmed. The brain MRI showed bilateral frontal lobe ( Figure 2C ) and left occipital lobe ( Figure 2D ) swelling with abnormal signals, indicating the persistence of CNS leukemia. The treatment process of case 2 is depicted in  Figure 2E .