Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired SAA Receiving sUCBT

Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired Severe Aplastic Aplasia Receiving Single Cord Blood Transplant: A Multi-center, Single-arm Study

To evaluate the safety and efficacy of Single Umbilical Cord blood transplantation (sUCBT) containing low dose ATG based conditioning regimen in the treatment of acquired Severe Aplastic Anemia (SAA).

Hematopoietic stem cell transplantation (HSCT) from HLA-compatible sibling donors is the standard preferred therapy for Severe Aplastic Anemia (SAA). At present, HLA-compatible donors in China fail to meet the needs of patients for transplantation. Umbilical Cord blood transplantation (UCBT) is an alternative treatment for patients with emergency conditions who lack compatible sibling donors, have failed immunosuppressant therapies or cannot wait for unrelated fully compatible donors. However, implantation failure is one of the main problems in UCBT for SAA due to the low cord blood stem cells. Nowadays, there is no consensus on the optimal conditioning regimen for UCBT treatment of SAA, and whether ATG should be added to the conditioning regimen is still controversial. Early clinical studies in UCBT have shown that the sufficient ATG in the conditioning regimen will lead to a decrease rate of implantation rate and affect survival of UCBT ultimately. However, a range of recent studies have found that with the addition of low-dose ATG, T cell reconstitution seems to outperform bone marrow or peripheral blood stem cell transplantation. Therefore, how to properly use ATG to both retain its effective GVHD prevention effect and reduce its impact on immune reconstruction has important clinical significance for improving the transplantation efficacy. In this study, a multicenter clinical study will be conducted to observe the safety and efficacy of UCBT with low dose ATG in the treatment of SAA and the long-term quality of life of patients.

Inclusion Criteria:

• Patients diagnosed with severe aplastic anemia who do not respond to initial diagnosis or immunosuppressive therapy;
• Patients meet diagnostic criteria for severe aplastic anemia (Camitta criteria);
• Age from 1 to 50 years old, male or female;
• Patients without HLA-matched sibling or unrelated donors avaliable;
• Patients who have undergone unrelated cord blood transplantation need to have HLA high-resolution matching、TNC (before cord blood freezing)≥3.0×107/kg、CD34+(before cord blood freezing)≥1.5×107/kg、tubule recovery rate≥80%;
• patients and their family members or guardians agreed to the study and signed informed consent;
• No severe organ failure;
• ECOG score≤2 and HCT-CI≤2;
• serum ferritin (SF)<1000ug/L;
• women of reproductive agemust have a negative pregnancy test and agree to use effective contraception during treatment and for one year thereafter.

Exclusion Criteria:

• patients with inherited bone marrow failure syndromes;
• Positive for HLA-A, B, Cw, DRB1, DQB1, DPB1 site-specific HLA antibodies for donor cord blood with solid-phase fluorescence assay;
• patients who have previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• Uncontrolled bacterial, viral, or fungal infections;
• HIV infection or active viral hepatitis B or C infection;
• Pregnant or breastfeeding women;
• patients with a history of primary malignancy within 3 years prior to transplant treatment;
• patients receiving ATG treatment within 2 weeks before transplantation;
• patients with drug dependent or uncontrolled mental illness or cognitive impairment;
• Participants in other similar clinical studies within 3 months;
• Patients allergic to ATG;
• patients considered unsuitable for inclusion by the researchers.