PD-1 blockade immunotherapy as a successful rescue treatment for disseminated adenovirus infection after allogeneic hematopoietic stem cell transplantation

The patient was a 54-year-old female who was diagnosed with diffuse large B-cell lymphoma in March 2020. She underwent 8 cycles of chemotherapy, including rituximab, and reached complete remission. The patient was subsequently diagnosed with MLL-ELL-positive acute myeloid leukemia, presumed to be treatment-related, in October 2022 and underwent 3 cycles of chemotherapy. She reached morphological remission and received haploidentical transplantation from her son on June 14, 2023. Unfortunately, she was diagnosed with EBV-positive PTLD at 2 months posttransplant. Immunosuppressive agents were rapidly tapered, and 3 doses of rituximab (375 mg/m2) were administered. The number of EBV copies in the blood decreased from 4.1*10E5 to 4.5*10E3 per milliliter after treatment. Moreover, the patient got intermittent fever, nausea, vomiting, diarrhea, and cough, and HAdV was detected positive in blood, throat swabs and stool specimens, at 3.7*10E4 copies/ml (cp/ml) in blood and 4.0*10E8 cp/ml in stool at 3 months posttransplant. She was diagnosed with dAdV disease, with upper respiratory tract, gastrointestinal tract and peripheral blood involved. After administration of 2 doses of cidofovir (5 mg/kg per week), the patient’s clinical symptoms and inflammatory indicators worsened, and her HAdV copy number continued to increase to 1.7*10E6 cp/ml in blood. Since PD-1 inhibitors have been successfully used to treat several chronic viral infections [6,7,8], it is speculated that PD-1 inhibitors might be effective for HAdV clearance. Therefore, 200 mg of sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) was administered as a salvage treatment with the prior informed consent of the patient. The viral copy numbers in blood and stool both decreased gradually and finally became negative 3 weeks later (Fig. 1). The patient developed acute graft-versus-host disease (GVHD) grade III in the liver. She was treated with cyclosporine and 3 doses of basiliximab (20 mg, twice a week) and showed a complete response. Surprisingly, the patient also became negative for peripheral EBV soon after receiving sintilimab. Routine bone marrow exams at 4 months posttransplant showed molecular relapse of leukemia, with MLL-ELL being positive, so the patient was treated with 100 mg of sintilimab again. MLL-ELL turned negative 1 month later and no recurrence of GHVD occurred. At 9 months posttransplant, the patient was in good condition with no recurrence of leukemia, HAdV infection or GVHD.

Fig. 1figure 1

Treatment process and development trends of viral copy numbers in the patient

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