Overview

Severe aplastic anemia is a life-threatening bone marrow failure disorder. Haploidentical hematopoietic stem cell transplantation has become an important curative treatment option for patients who do not have an HLA-matched sibling donor.

Traditionally, haploidentical transplantation for severe aplastic anemia uses a graft composed of granulocyte colony-stimulating factor-primed bone marrow plus peripheral blood stem cells. However, bone marrow collection is invasive and may increase donor burden. Peripheral blood stem cell collection is simpler and less invasive, but it remains unclear whether using peripheral blood stem cells alone provides similar clinical outcomes without increasing the risk of graft-versus-host disease.

This multicenter, randomized, open-label, non-inferiority trial will compare granulocyte colony-stimulating factor-primed peripheral blood stem cells alone with granulocyte colony-stimulating factor-primed bone marrow plus peripheral blood stem cells as graft sources for haploidentical transplantation in patients with severe or very severe aplastic anemia. Participants will be randomly assigned in a 1:1 ratio to either graft source group. The primary outcome is the cumulative incidence of grade II-IV acute graft-versus-host disease within 100 days after transplantation. Secondary outcomes include engraftment, chronic graft-versus-host disease, infections, immune reconstitution, survival, and donor safety.

Eligibility

Inclusion Criteria:

• Patients with newly diagnosed or relapsed severe aplastic anemia (SAA) or very severe aplastic anemia (vSAA) according to the Camitta criteria.
• SAA is defined as bone marrow cellularity \<25% and at least two of the following peripheral blood criteria: absolute neutrophil count \<0.5 × 10\^9/L, platelet count \<20 × 10\^9/L, or reticulocyte count \<20 × 10\^9/L.
• vSAA is defined as SAA with an absolute neutrophil count \<0.2 × 10\^9/L.
• Age 18 to 40 years.
• Availability of a haploidentical related donor.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate organ function, defined as follows:
• Cardiac function: left ventricular ejection fraction ≥50% and no severe arrhythmia.
• Hepatic function: total bilirubin ≤2 times the upper limit of normal and alanine aminotransferase/aspartate aminotransferase ≤3 times the upper limit of normal.
• Renal function: creatinine clearance ≥60 mL/min.
• No active infection.
• For women of childbearing potential, a negative pregnancy test is required.
• All patients must agree to use effective contraception during the study period.
• Written informed consent provided by the patient or legal representative.

Exclusion Criteria:

• Presence of hematologic malignancy or myelodysplastic syndrome-related chromosomal abnormalities, such as +8 or del(7q).
• Prior allogeneic hematopoietic stem cell transplantation or prior organ transplantation.
• Availability of an HLA-matched sibling donor.
• Active uncontrolled infection, including unresolved invasive fungal disease, active tuberculosis, sepsis, or other uncontrolled infections.
• Severe comorbidities, defined as a Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score ≥4, or uncontrolled autoimmune disease.
• Donor-related contraindications, including donor age \<12 years or \>65 years, donor body mass index \<18 or \>35 kg/m², contraindications to anesthesia, or contraindications to bone marrow harvest.
• Psychiatric illness that prevents cooperation with study procedures, or any condition considered by the investigator to make the patient unsuitable for study participation.