The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA

Peking University People's Hospital160 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

160

Conditions

Severe Aplastic Anemia

Interventions

Eligibility

Sex: ALLMin age: 1 YearMax age: 50 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Failure free survival

Failure free survival was defined as survival with a response to therapy.

Time frame: 1 year post HSCT

Secondary Outcomes

The incidence of mixed chimerism

The mixed chimerism was defined as the presence of 5%-95% donor haematopoietic cells.

Time frame: 1 year post HSCT

Regimen related toxicity

The regimen related toxicity (RTT) was measured according to the Seattle Toxicity Criteria (Bearman et al, 1988).

Time frame: 100 days post HSCT

Myeloid and platelet engraftment

Myeloid and platelet engraftment were defined as international criteria.

Time frame: 100 days post HSCT

The incidence of graft versus host disease

The severity of acute and chronic GVHD was evaluated according to standard criteria.

Time frame: 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.

Time frame: 100 days post HSCT

The incidence of Transplantation related mortality

Transplantation related mortality was defined as death without disease progression.

Time frame: 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

Time frame: 1 year post HSCT

The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts