Anti-CD123 CAR-T therapy combined with autologous SCT and venetoclax maintenance in refractory BPDCN ineligible for allogeneic transplantation: a case report and review of the literature

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with limited therapeutic options for patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). While CD123-targeted therapies and CAR T-cell infusion have shown promise, achieving durable remission without consolidative transplantation remains challenging. We report a pioneering “triple-integrated” consolidation strategy in a 55-year-old male with relapsed/refractory BPDCN and central nervous system involvement who lacked a suitable HLA-matched donor. After achieving a complete metabolic response with persistent bone marrow minimal residual disease (MRD) following Hyper-CVAD chemotherapy, the patient underwent high-dose conditioning and autologous stem cell transplantation (ASCT) sequentially followed by autologous CD123 CAR T-cell infusion (1.74×106/kg). The clinical course was complicated by Grade 3 cytokine release syndrome and suspected immune effector cell-associated HLH-like syndrome (IEC-HS), which were successfully managed with glucocorticoid and emapalumab. Notably, ASCT served as a “hematopoietic rescue” for CAR-T-induced prolonged cytopenia. To prevent late clonal escape, maintenance therapy with the BCL-2 inhibitor venetoclax was initiated post-transplant. The patient achieved sustained MRD-negative CR with a disease-free survival exceeding 13 months. This multimodal paradigm—combining intensive cytoreduction, targeted immunotherapy with marrow rescue, and molecular maintenance—provides a feasible and potentially curative alternative for BPDCN patients in the “no-donor” setting.