The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA

Study Overview
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Brief Summary
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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.

Official Title
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To Evaluate Different Conditioning Regimens for HLA Matched Donor Transplantation in Severe Aplastic Anemia: a Prospective, Multicenter, Randomized Controlled Study

Conditions
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Severe Aplastic Anemia

Intervention / Treatment
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* Drug: Busulfan
* Drug: Flu/Cy/ATG or Cy/ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as SAA/vSAA Indication for hematopoietic stem cell transplantation Available HLA matched sibling or unrelated donor No active infection No serious organ damage: liver and kidney function (ALT and AST < 2.5 times normal value, normal renal function, no cardiac insufficiency) Signed informed consent High risk factors of mixed chimerism, at least one of the following Age < 18 years old Ferritin level ≥2500ng/ml before transplantation Exclusion Criteria: Age > 50 years old ECOG≥3 Active infections that were difficult to control Severe liver and kidney dysfunction Mental illness Not signing the informed consent pregnant or lactating women Any condition considered by the investigators to be unsuitable for enrollment

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Busulfan included group<br>The conditioning regimens were Bu/Flu/Cy/ATG or Bu/Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity. | Drug: Busulfan<br>* Conditioning regimens were Bu/Flu/Cy/ATG or Bu/Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.<br>|
| Other: Control group<br>The conditioning regimens were Flu/Cy/ATG or Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity. | Drug: Flu/Cy/ATG or Cy/ATG<br>* Conditioning regimens were Flu/Cy/ATG or Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure free survival | Failure free survival was defined as survival with a response to therapy. | 1 year post HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of mixed chimerism | The mixed chimerism was defined as the presence of 5%-95% donor haematopoietic cells. | 1 year post HSCT | 
| Regimen related toxicity | The regimen related toxicity (RTT) was measured according to the Seattle Toxicity Criteria (Bearman et al, 1988). | 100 days post HSCT | 
| Myeloid and platelet engraftment | Myeloid and platelet engraftment were defined as international criteria. | 100 days post HSCT | 
| The incidence of graft versus host disease | The severity of acute and chronic GVHD was evaluated according to standard criteria. | 100 days post HSCT for aGvHD and 1 year post HSCT for cGvHD | 
| The incidence of CMV and EBV reactivation | The incidence of CMV and EBV reactivation was defined as CMV and EBV viremia. | 100 days post HSCT | 
| The incidence of Transplantation related mortality | Transplantation related mortality was defined as death without disease progression. | 1 year post HSCT | 
| The probability of Overall survival | Overall survival was defined as the time from transplantation to death from any cause or to the last follow-up | 1 year post HSCT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HLA matched donor transplantation