NAC for Hematopoietic Recovery in Low/Intermediate-Risk AML After CR: A Randomized Controlled Study

• N-acetyl-L-cysteine (NAC) (Drug): N-Acetyl-L-cysteine (NAC) 400 mg oral tablet, three times daily for 28 consecutive days, administered in addition to standard post-induction chemotherapy care for acute myeloid leukemia

Primary outcomes

• Time to Platelet Recovery [60 days post-chemotherapy]: The time from Day 1 of chemotherapy until the first day that the platelet count reaches ≥20×10⁹/L and remains stable for 7 consecutive days without transfusion support.

Secondary outcomes

• Time to Neutrophil Recovery [60 days post-chemotherapy]: The time from Day 1 of chemotherapy until the first day that the absolute neutrophil count (ANC) reaches ≥0.5×10⁹/L for 3 consecutive days, or the white blood cell (WBC) count reaches ≥1.0×10⁹/L for 3 consecutive days
• Total Dose of G-CSF [60 days post-chemotherapy]: The total dose of Granulocyte Colony-Stimulating Factor (G-CSF) administered, calculated at a starting dose of 5 µg/kg body weight when the WBC count is <0.5×10⁹/L, until neutrophil recovery is achieved
• Total Volume of Platelet Transfusions [60 days post-chemotherapy]: The total volume of platelet transfusions administered after the initiation of chemotherapy, when the platelet count is <10×10⁹/L
• Total Volume of Red Blood Cell [60 days post-chemotherapy]: The total volume of red blood cell transfusions administered after the initiation of chemotherapy, when the hemoglobin level is <70 g/L
• Complete Remission (CR) Rate [35 days post chemotherapy]: The proportion of patients achieving a best overall response of Complete Remission (CR) as determined by the investigator per ELN guidelines. CR is defined as: Bone marrow (BM) blasts <5%; no blasts or Auer rods-containing blasts in peripheral blood; no extramedullary disease; Absolute Neutrophil Count (ANC) ≥1.0×10⁹/L; and platelet count ≥100×10⁹/L
• CR + CRi Rate [35 days post chemotherapy]: The proportion of patients achieving a best overall response of Complete Remission (CR) or Complete Remission with incomplete blood count recovery (CRi) as determined by the investigator per ELN guidelines. CRi is defined as: Bone marrow (BM) blasts <5%; no blasts or Auer rods-containing blasts in peripheral blood; no extramedullary disease; ANC <1.0×10⁹/L or platelet count <100×10⁹/L, and transfusion independence
• Overall Survival (OS) [24 months post chemotherapy]: The time from diagnosis to death from any cause
• Relapse-Free Survival (RFS) [24 months post CR]: The time from achieving Complete Remission (CR) until relapse or death from any cause, while maintaining continuous CR status
• Adverse Events [30 days after the last dose of NAC]: Adverse events related to oral NAC administration, including hepatic function, renal function, or respiratory syndrome evaluated according to the CTCAE version 4.0

Other outcomes

• Exploratory objectives [60 days post-chemotherapy]: To evaluate the influence of NAC in the bone marrow microenvironment among patients with AML after chemotherapy

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Newly diagnosed acute myeloid leukemia (AML, excluding AML-M3)
2. Low-risk or intermediate-risk AML per the 2022 European Leukemia Net (ELN) genetic risk stratification guidelines
3. Aged 18 to 65 years (inclusive)
4. Induction chemotherapy with the HAA regimen. For patients diagnosed with AML harboring FLT3-ITD mutation, treatment with the HAA regimen combined with the FLT3 inhibitor Sorafenib is permitted.
5. No severe organ dysfunction
6. No uncontrolled active infection
7. Signed informed consent, and capable of adhering to study procedures and follow-up protocols

Exclusion Criteria:

1. Non-remission acute leukemia
2. Hypersensitivity to N-Acetylcysteine (NAC) or a history of bronchial asthma
3. Expected survival of less than 30 days after the end of chemotherapy
4. Uncontrolled infection prior to treatment
5. Cardiac dysfunction (specifically congestive heart failure, unstable coronary artery disease, or severe ventricular arrhythmia requiring antiarrhythmic therapy)
6. Respiratory failure (arterial partial pressure of oxygen PaO₂ ≤ 60 mmHg)
7. Hepatic abnormality: Total serum total bilirubin ≥ 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥ 2 times ULN
8. Renal abnormality: Serum creatinine ≥ 1.5 times ULN, or creatinine clearance < 30 mL/min
9. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3
10. Any other condition unsuitable for trial participation (determined by the investigator)

• Xiao-Jun Huang, Principal investigator, Peking University People's Hospital