Iptacopan combined with immunosuppressive therapy for aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome

RATIONALE: Aplastic anemia-paroxysmal nocturnal hemoglobinuria (AA-PNH) syndrome is a rare acquired hematopoietic stem cell disorder. Patients who respond poorly to conventional immunosuppressive therapy (IST) and corticosteroids face limited therapeutic options and a poor prognosis. This article reports on the use of iptacopan combined with IST for AA-PNH syndrome. PATIENT CONCERNS: A previously healthy 24-year-old Han Chinese male presented with dizziness and fatigue and was found to have pancytopenia. He was initially treated with cyclosporine. However, 2 years after discontinuation, he developed acute hemolysis. After treatment with iptacopan, the patient's hemolysis was quickly controlled, but he still required blood transfusions. DIAGNOSES: The patient was initially diagnosed with aplastic anemia through bone marrow examination, along with a paroxysmal nocturnal hemoglobinuria clone. After recurrent acute hemolysis, reexamination of the bone marrow and flow cytometry revealed partial deficiency of cluster of differentiation (CD) 55/CD59, and fluorescently labeled aerolysin-negative cells accounted for more than 90% of granulocytes and monocytes. Eventually, the diagnosis of AA-PNH syndrome was made. INTERVENTIONS: After acute hemolysis was initially managed with steroids and IST, the patient was started on iptacopan to achieve rapid hemolysis control. Given persistent transfusion dependence due to bone marrow hypoplasia, immunosuppressants and hematopoietic stimulants (danazol and eltrombopag) were added while continuing iptacopan. The hematopoietic stimulants were discontinued after 3 months due to abnormal liver function tests, and the patient was maintained on iptacopan combined with IST. OUTCOMES: Iptacopan rapidly and effectively controlled hemolysis, and no breakthrough hemolysis, extravascular hemolysis, or drug-related adverse events were observed. Critically, iptacopan served as a bridge to control hemolysis, while the subsequent addition of IST (tacrolimus/cyclosporine) addressed the underlying autoimmune bone marrow failure. After combined treatment with iptacopan and IST, the patient's blood cell count gradually recovered, hemoglobin returned to normal levels, and blood transfusion was no longer required. LESSONS: This case suggests that iptacopan combined with IST may represent a potentially effective and safe therapeutic option for AA-PNH syndrome that is refractory to conventional IST and corticosteroids. Especially for AA-PNH patients with impaired bone marrow function and continuous dependence on blood transfusion, iptacopan combined with IST may be an effective and well-tolerated treatment regimen.