Elderly AML patients receiving conventional chemotherapy have poor prognosis. Allo-HSCT offers better long-term survival than chemotherapy, while high TRM limits its use. Current research focuses more on improving conditioning regimens to reduce TRM. Studies suggest Bu/Flu/Cy/ATG are safer and more effective for elderly AML haplo-HSCT, lowering TRM. However, prospective randomized trials are lacking. This study aims to compare Bu/Flu/Cy/ATG vs. Bu/Cy/ATG to determine if TRM can be reduced in elderly AML undergoing haplo-HSCT.
The prognosis of elderly patients with acute myeloid leukemia (AML) undergoing conventional chemotherapy is poor. Compared with chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve long-term survival in elderly patients. However, the high transplantion-related mortality (TRM) limited its application. Currently, the top priority in transplantation for elderly AML patients is to reduce TRM through methods such as optimizing conditioning regimens, reducing graft-versus-host disease (GVHD), and preventing infections. Present research primarily focuses on optimizing conditioning regimens. Both domestic and international studies, as well as our team's preliminary research, suggest that replacing cyclophosphamide (Cy) with fludarabine (Flu) can reduce toxicity. Earlier prospective single-arm clinical study in our team confirmed that the Bu/Flu/Cy/ATG regimen is a safe and effective conditioning protocol for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in elderly AML patients. This study aims to use a prospective randomized controlled trial to verify whether the Bu/Flu/Cy/ATG conditioning regimen can reduce TRM compared with the Bu/Cy/ATG regimen in elderly AML patients undergoing haplo-HSCT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
307
The Bu/Flu/Cy/ATG conditioning regimen consists of the following components: Ara-C (2 g/m²/day, injected i.v.) on days-10 and-9; Bu (0.8 mg/kg, q6h, injected i.v.) on days -8 to -6; Flu (30 mg/m²/day, injected i.v.) from day-6 to day-2; Cy (1.0 g/m²/day, injected i.v.) on days-5 and-4; and ATG (2.5 mg/kg/day) on days-5 to -2.
The Bu/Cy/ATG conditioning regimen consists of the following components: Ara-C (4 g/m²/day, injected i.v.) on day-9; Bu (0.8 mg/kg, q6h, injected i.v.) on days -8 to -6; Cy (1.8 g/m²/day, injected i.v.) on days-5 and-4; and ATG (2.5 mg/kg/day) on days-5 to -2.
Peking University People's Hospital
Beijing, China
Transplant-related mortality (TRM)
TRM is defined as death due to any transplantation-related cause other than disease relapse. Transplant-related mortality will be calculated using a competing risks model.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.
Toxicity of conditioning
Toxicity of conditioning within 28 days of HSCT can be graded according to Common Terminology Criteria for Adverse Events (CTCAE): 1.Grade 1: Mild toxicity that does not require medical intervention. 2.Grade 2: Moderate toxicity that may require medical intervention. 3.Grade 3: Severe toxicity that requires significant medical intervention, hospitalization, or results in lasting effects. 4.Grade 4: Life-threatening toxicity, potentially requiring intensive care. 5.Grade 5: Death caused by the toxicity reaction.
Time frame: From HSCT to the follow-up assessment at 28 days and 100 days post-treatment.
Engraftment
Platelet engraftment was defined as the first of seven consecutive days with a platelet count \>20 × 109/L without transfusion support. Neutrophil engraftment was defined as the first of three consecutive days with an ANC \> 0.5 × 109/L.
Time frame: Platelet engraftment was assessment at 28 days post-transplantation.
GVHD
Acute GVHD was classified as symptom presentation before 100 days after haplo-HSCT and chronic GVHD was classified as symptom presentation \>100 days after haplo-HSCT. Each organ (skin, liver, and gut) was staged 1 through 4 for Acute GVHD according to modified criteria based on the schema of the Mount Sinai Acute GVHD International Consortium (MAGIC), and patients were also assigned a grade of acute GVHD (I through IV) based on overall severity. Chronic GVHD was graded in accordance with the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease Consensus Criteria.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.
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Overall Survival
The time from haplo-HSCT to death from any cause in patients with AML. Overall survival will be calculated using the Kaplan-Meier method.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.
Cumulative Incidence of Relapse
Relapse was defined as disease recurrence.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.
Leukemia-free survival
Leukemia-free survival (LFS) was defined as the time from transplantation to relapse, disease progression, or death, whichever occurred first.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.
Event-Free Survival
Event-Free Survival (EFS) was defined as the time from transplantation to relapse, graft failure, death from any cause, or requirement for additional anti-leukemic therapy.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.
Viral Infection
Detection of CMV-DNA and EBV-DNA in peripheral blood twice a week.
Time frame: From HSCT to the follow-up assessment at 12 months post-treatment.