This study aims to evaluate the efficacy and safety of prophylactic oral N-acetylcysteine (NAC) for facilitating platelet engraftment in patients with severe aplastic anemia (SAA) receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This is a prospective, multicenter, randomized controlled trial enrolling a total of 142 patients with SAA scheduled for their first haplo-HSCT, who will be randomly assigned at a 1:1 ratio to the NAC prophylaxis group or the control group, with 71 subjects in each arm. Patients in the intervention group will receive oral NAC 400 mg three times daily from Day -14 before transplantation to Day +60 post-transplant, while the control group will receive no prophylactic NAC, with all other transplant-related treatments identical between the two groups. The primary endpoint is the cumulative platelet engraftment rate by 2 months after transplantation. Secondary endpoints cover neutrophil engraftment rate, incidence of poor hematopoietic reconstitution, cumulative blood product transfusion volume, graft-versus-host disease (GVHD), overall survival, GVHD-free and failure-free survival, and biomarkers reflecting bone marrow hematopoietic microenvironment reconstruction. Safety outcomes will be assessed via adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Statistical analyses will be performed using R 4.4.0 software, primarily adopting competing risk models and the Kaplan-Meier method based on full analysis set, per-protocol set and safety set. This trial will clarify intergroup differences in platelet recovery, other efficacy endpoints and safety profiles, verify the clinical benefits and safety of NAC, and generate high-quality clinical evidence for prophylactic intervention targeting platelet engraftment after haplo-HSCT in SAA patients to optimize clinical management strategies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
142
Oral NAC capsules, 400 mg per dose, administered three times daily. Treatment starts at Day -14 before transplantation and continues until Day +60 after transplantation.
Cumulative incidence of platelet engraftment by 2 months after transplantation
Platelet engraftment was characterized as the first day with a platelet count of at least 20 × 10\^9/L without transfusion support for seven consecutive days.
Time frame: 2 months post-HSCT
Cumulative incidence of neutrophil engraftment by 2 months after transplantation
Neutrophil engraftment was defined as the first of three consecutive days with a neutrophil count of at least 0.5 × 10\^9/L
Time frame: 2 months post-HSCT
Incidence of poor hematopoietic reconstitution by 2 months post-transplant
Poor hematopoietic reconstitution includes delayed platelet engraftment and poor graft function (PGF). Delayed platelet engraftment: platelet \<20×10\^9/L or persistent platelet transfusion dependence at Day +60. PGF refers to persistent cytopenia with complete donor chimerism and hypoplastic marrow.
Time frame: 2 months post-HSCT
Cumulative volume of blood product transfusions
Total units of platelet and red blood cell transfusions received by each patient. Transfusion standards follow institutional clinical guidelines for anemia and severe thrombocytopenia.
Time frame: From pre-transplant Day -14 to post-transplant Day +60
Cumulative incidence of acute and chronic graft-versus-host disease (aGVHD/cGVHD)
aGVHD was graded by modified Glucksberg criteria within 100 days; chronic GVHD was diagnosed by National Institutes of Health consensus criteria within 1 year post-transplant.
Time frame: 100 days for aGVHD; 1 year for cGVHD after transplantation
1-year overall survival (OS)
OS was defined as the duration from HSCT to death from any cause or the date of the last follow-up.
Time frame: 1 year after transplantation
1-year graft-versus-host disease-free, failure-free survival (GFFS)
GFFS was defined as the absence of grade III-IV acute GVHD, extensive chronic GVHD, graft failure, or death from any cause.
Time frame: 1 year after transplantation
Bone marrow endothelial progenitor cell (EPC) count and intracellular reactive oxygen species (ROS) level
Laboratory biomarkers reflecting bone marrow hematopoietic microenvironment reconstruction, including EPC quantity and intracellular ROS level detected at scheduled bone marrow puncture time points.
Time frame: Baseline (pre-transplant), post-transplant 1 months and 2 months
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