Severe Aplastic Anemia
Conditions
Keywords
HLA matched donor transplantation
Brief summary
Hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA) -matched donor is an effective option for severe aplastic anemia (SAA), but there is no standardized and recommended conditioning regimen. The occurrence of mixed chimerism after transplantation is associated with secondary graft failure and poor failure-free survival. Previous studies have shown that Fludarabine (Flu)/ Cyclophosphamide (Cy)/ antithymocyte globulin (antithymocyte globulin), ATG) and Cy/ATG conditioning regimens had higher rates of mixed chimerism and poorer failure-free survival. A small cohort study has suggested that adding busulfan to Flu/Cy/ATG or Cy/ATG can reduce the incidence of mixed chimerism and improve failure-free survival. This study was a prospective, multicenter, randomized controlled trial to compare the efficacy and safety of different conditioning regimens in the treatment of severe aplastic anemia (SAA) after hematopoietic stem cell transplantation (HSCT) from HLA-identical sibling or unrelated donor.
Interventions
DRUGBusulfan
Conditioning regimens were Bu/Flu/Cy/ATG or Bu/Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.
DRUGFlu/Cy/ATG or Cy/ATG
Conditioning regimens were Flu/Cy/ATG or Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.
Sponsors
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed as SAA/vSAA 2. Indication for hematopoietic stem cell transplantation 3. Available HLA matched sibling or unrelated donor 4. No active infection 5. No serious organ damage: liver and kidney function (ALT and AST \< 2.5 times normal value, normal renal function, no cardiac insufficiency) 6. Signed informed consent 7. High risk factors of mixed chimerism, at least one of the following 1. Age \< 18 years old 2. Ferritin level ≥2500ng/ml before transplantation
Exclusion criteria
1. Age \> 50 years old 2. ECOG≥3 3. Active infections that were difficult to control 4. Severe liver and kidney dysfunction 5. Mental illness 6. Not signing the informed consent 7. pregnant or lactating women 8. Any condition considered by the investigators to be unsuitable for enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure free survival | 1 year post HSCT | Failure free survival was defined as survival with a response to therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Regimen related toxicity | 100 days post HSCT | The regimen related toxicity (RTT) was measured according to the Seattle Toxicity Criteria (Bearman et al, 1988). |
| Myeloid and platelet engraftment | 100 days post HSCT | Myeloid and platelet engraftment were defined as international criteria. |
| The incidence of graft versus host disease | 100 days post HSCT for aGvHD and 1 year post HSCT for cGvHD | The severity of acute and chronic GVHD was evaluated according to standard criteria. |
| The incidence of mixed chimerism | 1 year post HSCT | The mixed chimerism was defined as the presence of 5%-95% donor haematopoietic cells. |
| The incidence of Transplantation related mortality | 1 year post HSCT | Transplantation related mortality was defined as death without disease progression. |
| The probability of Overall survival | 1 year post HSCT | Overall survival was defined as the time from transplantation to death from any cause or to the last follow-up |
| The incidence of CMV and EBV reactivation | 100 days post HSCT | The incidence of CMV and EBV reactivation was defined as CMV and EBV viremia. |
Countries
China
Contacts
Primary ContactZheng-Li Xu, M.D.
Outcome results
None listed