CELL INTELLIGENCE · 肿瘤细胞治疗研究

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) represents a potentially life-threatening and grave complication that can arise following solid organ transplantation (SOT). Clinically, extranodal involvement in PTLD is frequent, whereas involvement of the central nervous system (CNS) is relatively rare and frequently associated with a poor prognosis. Currently, there is no standardized therapeutic approach for CNS-PTLD. CASE DESCRIPTION: We report a pediatric patient who suffered from multiple recurrences of CNS-PTLD after liver transplantation. The patient was Epstein-Barr virus (EBV)-negative before transplantation but developed PTLD involving lymph node, liver, and multiple bones 2 years after liver transplantation, accompanied by elevated EBV-DNA in peripheral blood (PB). As the lesion was systemic and CD20-positive, we chose to use rituximab (RTX) monotherapy and achieved remission. However, after 3 cycles of RTX, the child developed neurological symptoms such as facial nerve palsy and mouth deviation. Brain magnetic resonance imaging (MRI) revealed a mass in the inner ear and thickening of the facial nerve, suggesting that the disease had invaded the CNS. Therefore, we upgraded the treatment plan to R-CHOP chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), and achieved a complete remission (CR). Following 2 cycles of R-CHOP, the patient experienced facial nerve palsy again, and brain MRI indicated a lesion in the left cerebellopontine angle region, suggesting disease recurrence. Re-treatment with 4 cycles of R-CHOP provided minimal symptomatic relief, and follow-up MRI demonstrated progressive multiple intracranial lesions. Brain biopsy confirmed CNS-PTLD [EBV-positive Burkitt's lymphoma (BL)]. Due to the patient's resistance to standard chemotherapy (R-CHOP) and the limited location of the lesion in the CNS, we switched to a more central-permeable treatment regimen. Then the patient achieved CR following treatment with high-dose methotrexate (HD-MTX) combined with intrathecal methotrexate (IT-MTX), and subsequently underwent timely chimeric antigen receptor T-cell (CAR-T) therapy to consolidate the therapeutic effect and prevent recurrence. The patient currently maintains sustained CR. CONCLUSIONS: We observe that the combination of HD-MTX and intrathecal chemotherapy exhibits remarkable efficacy in managing post-transplant CNS-PTLD that is resistant to conventional R-CHOP chemotherapy. CAR-T therapy emerges as a potential option for patients suffering from relapsed or refractory CNS-PTLD.