Allogeneic hematopoietic stem cell transplantation achieves complete response in refractory primary mediastinal large B-cell lymphoma after the failure of chemotherapy, CAR-T therapy, and PD-1 blockade.

Primary mediastinal large B-cell lymphoma (PMBCL) typically responds to chemotherapy, and immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapy and the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab have shown promise in relapsed or refractory cases. However, the sequential use of multiple immunotherapies for PMBCL remains poorly characterized. Here, we report a case of a 19-year-old female with PMBCL involving the mediastinum and multiple extranodal sites. After a partial response to chemotherapy, she developed a central nervous system relapse that responded to high-dose methotrexate, and the number of regrowing mediastinal lesions was reduced by radiotherapy. Subsequently, new hepatic lesions that were refractory to both CAR-T therapy and pembrolizumab emerged. Following localized liver radiotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed, resulting in complete response. Early post-transplant, she developed a hepatitis variant of acute graft-versus-host disease, which may have reflected a graft-versus-lymphoma (GVL) effect. Despite maintaining response, the patient died one year later form a disseminated infection with multitriazole-resistant Aspergillus fumigatus. This case highlights both the potential curative role and the substantial risks of allo-HSCT in PMBCL refractory to multiple immunotherapies. The pre-transplant use of pembrolizumab and localized radiotherapy may influence transplant outcomes and warrants further investigation.