The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
Aim: To evaluate if additional cord blood transfusion could accelerate the hematopoietic
 reconstitution in severe aplastic anemia(SAA) patients receiving immunosuppressive therapy
 (IST).

 Study design: open-labed, prospective, multicenter, randomized control study Number of
 subjects: 60 each group

 Treatment:

 IST group: ATG (Thymoglobuline®, Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A (CSA) Cord
 blood transfusion group: In addition to the same dose and course of ATG and CSA , one unit of
 cord blood having no more than 2 HLA-A, B or DRB1 mismatches is transfused 24h after last
 dose of ATG administration.
Eligible patients should be under 60 years old with confirmed SAA, without HLA matched
 siblings and previous ATG treatment history. Patients will be excluded if they present any
 fatal disease, including respiratory failure, heart failure, liver or kidney function failure
 et al or severely allergic to biologic products.

 To evaluate if additional cord blood transfusion could accelerate the hematopoietic
 reconstitution in severe aplastic anemia(SAA) patients receiving IST therapy, 120 eligible
 patients will be randomized to two groups, the IST group and the cord blood transfusion
 group. Patients in the IST group receive standard IST which including ATG (Thymoglobuline®,
 Genzyme) 3.5mg/kg/d×5d plus oral cyclosporine A（CSA ) started from 5mg/kg/d and adjusted to
 maintain trough serum concentration of 200-300ng/ml. While patients in the cord blood
 transfusion group receive the same dose and course of ATG and CSA as the control group and
 one unit of cord blood having no more than 2 HLA-A, B and DRB1 mismatches is transfused 24h
 after last dose of ATG administration.

 The neutrophil recovery day is defined as the first day of 3 consecutive days during which
 the absolute neutrophil count (ANC) is >0.5×109/L, without G-CSF adminstration. Platelet
 recovery day is deﬁned to have occurred on the ﬁrst of 7 consecutive days with a blood
 platelet count (BPC) of >20×109/L, without transfusion support. Response (CR, PR or NR) is
 evaluated on 3, 4, 6,9, 12, 18 and 24months after treatment.

 The primary end point is the neutrophil recovery day and second end points are response rate
 (CR+PR), treatment related mortality, disease free survival and overall survival.

 .
Inclusion Criteria:

 1．Diagnosis of AA confirmed by bone marrow aspirate and biopsy, myelodysplastic syndrome
 and paroxysmal nocturnal hemoglobinuria were excluded. To confirm severe AA, the patient
 must fulfill at least two of the criteria: i) ANC<0.5×109/L,ii)PLT<20×109/L and iii)
 Ret<20×109/L ,in addition, ANC<0.5×109/L must be included.

 2. Under 60 years old, male or female.

 3. No HLA matched siblings.

 4. No previous ATG treatment history.

 5. Performance status score no more than 2 (ECOG criteria).

 6．Adequate organ function as defined by the following criteria:ALT, AST and total serum
 bilirubin <2×ULN (upper limit of normal) Serum creatinine and BUN <1.25×ULN.

 7. Adequate cardiac function without acute myocardial infarction, arrhythmia or
 atrioventricular block, heart failure, active rheumatic heart disease and cardiac
 dilatation.

 8．Signed and dated informed consent document indicating that the patient (or legally
 acceptable representative) has been informed of all pertinent aspects of the trial prior to
 enrollment.

 9. Willingness and ability to comly with scheduled visits, treatment plans, laboratory
 tests, and other study procedures.

 Exclusion Criteria:

 1. Presence of any condition inappropriate for HSCT.

 2. Presence of any fatal disease, including respiratory failure, heart failure, liver or
 kidney function failure et al.

 3．Severely allergic to biologic products.

 4．Pregnancy or breastfeeding.

 5．Current treatment on another clinical trail.

 6．Any other condition the investigator judged the patient inappropriate for entry into this
 study.