Refractory/relapsed aplastic anemia (AA) in adults remains a clinical challenge that is frequently encountered and urgently needs to be resolved. Salvage treatment should prioritize hematopoietic stem cell transplantation (HSCT). Unrelated cord blood is an ideal source of hematopoietic stem cells due to its easy availability, low immunogenicity, and low incidence of chronic graft-versus-host disease (cGVHD) after transplantation.The optimization of the conditioning regimen for UCBT is a crucial factor in determining patient outcomes.
This is a Phase II clinical study. A total of 11 adult patients with refractory/relapsed AA will be treated with a UCBT regimen based on a TMI-based conditioning regimen. Patients who meet the inclusion/exclusion criteria will sign an informed consent form before undergoing cord blood transplantation. The efficacy (12-month EFS) and safety of the regimen will be assessed 12 months after transplantation.
Age ≥18 years and <50 years, regardless of gender.
Diagnosis of AA according to the guidelines of the British Society for Haematology. The bone marrow shows hypocellularity, without infiltration of abnormal cells or marrow fibrosis. The peripheral blood must meet at least two of the following three criteria: absolute neutrophil count (ANC) <1.5×10⁹/L; platelet count <50×10⁹/L; hemoglobin <100 g/L. Based on the severity of the disease, AA is classified into severe aplastic anemia (SAA) and non-severe aplastic anemia (NSAA).
Meet the criteria for refractory AA: ①SAA: no response to first-line ATG + CSA treatment for more than 6 months; ②NSAA: ①persistent transfusion dependence of two or more blood cell lines, ②meet any of the following criteria: no response to immunosuppressive therapy with cyclosporine for more than 12 months, or no response to androgen and/or TPO receptor agonist therapy for more than 6 months, ④or progression to SAA; Meet the criteria for relapsed AA: initially effective to first-line immunosuppressive therapy, but pancytopenia recurs after reduction or discontinuation of immunosuppressive therapy, meeting the criteria for SAA.
Karnofsky score ≥60, ECOG score ≤2, HCT-CI index ≤2.
Pancytopenia and hypoplastic marrow diseases caused by other reasons (including PNH, etc.).
Use of intermediate or high doses of cyclophosphamide (≥20mg/kg/d) for immunosuppressive therapy within 3 months before enrollment.
History of hematopoietic stem cell transplantation.
Known or suspected contraindications or allergies to fludarabine, melphalan, or other drugs.