Efficacy and Safety of Sirolimus With or Without Cyclosporin A in Chinese Patients With Aplastic Anemia Refractory/Intolerant to Cyclosporin A

Inclusion criteria

• Age ≥ 18 years;
• Diagnosed with acquired aplastic anemia (AA), excluding congenital AA;
• At least one of the following criteria met at enrollment: hemoglobin < 100 g/L, platelets < 50 × 10⁹/L, or neutrophils < 1.0 × 10⁹/L;
• At enrollment, meeting at least one of the following conditions:

① Cyclosporine A (CsA) ineffective: (CsA) used for at least 3 months without achieving partial response (PR), or disease relapse occurred;

② CsA intolerant: Unsuitable for standard dose CsA treatment due to adverse events or underlying conditions.

• No active infections;
• Not pregnant or breastfeeding;
• Willing to sign the consent form;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

Exclusion criteria

• Pancytopenia caused by other reasons, such as myelodysplastic syndrome (MDS);
• Evidence of clonal hematopoietic system bone marrow diseases (e.g., MDS or acute myeloid leukemia, AML);
• Paroxysmal nocturnal hemoglobinuria (PNH) clone ≥ 50%;
• History of hematopoietic stem cell transplantation (HSCT) before enrollment;
• Previous use of sirolimus or allergy to sirolimus;
• Severe adverse events to CsA in the past, making it unsuitable for reuse;
• Uncontrolled infection or bleeding with standard treatment;
• Active infections with HIV, HCV, or HBV, liver cirrhosis, portal hypertension;
• Any concurrent malignancy within the past 5 years, except for localized basal cell carcinoma of the skin;
• History of thromboembolic events, myocardial infarction, or stroke (including antiphospholipid antibody syndrome), or current use of anticoagulants;
• Pregnant or breastfeeding women;
• Participation in other clinical trials within the past 3 months.