A Prospective Single-Arm Study of VABu Conditioning Regimen in Allo-HSCT for Low-Performance or High-Comorbidity AML Patients in CR1

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. For patients who are unfit for intensive chemotherapy due to poor performance status or high comorbidity burden, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potential curative treatment. However, these patients often have low transplantation rates and suboptimal outcomes with reduced-intensity conditioning regimens. Venetoclax combined with azacitidine has been established as the standard of care for unfit AML patients, demonstrating high remission rates and good tolerability. Building on this, our center has previously explored the VABu regimen (venetoclax, azacitidine, and busulfan) as a conditioning therapy in elderly AML patients undergoing allo-HSCT, with preliminary results showing reduced chemotherapy-related toxicity and a 2-year overall survival rate of approximately 70%.

This is a single-arm, prospective, single-center study. A total of 42 participants will be enrolled. Eligible participants are patients aged 18 to 70 years with non-APL AML who have achieved first complete remission (CR1), are classified as non-high-risk per ELN 2022 guidelines, and have either ECOG performance status ≥ 2 (not due to leukemia) or HCT-CI ≥ 2. All participants will receive the VABu conditioning regimen followed by allo-HSCT. The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, busulfan 0.8 mg/kg every 6 hours on days -5 to -3, and antithymocyte globulin (ATG) at 2.5 mg/kg/day according to donor type (haploidentical/unrelated donors on days -5 to -2, or matched sibling donors on days -3 to -2). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis.

The primary outcome measure is 2-year overall survival (OS). Secondary outcome measures include 2-year relapse-free survival (RFS), transplant-related mortality (TRM), engraftment failure rate, bloodstream infection (BSI), and 2-year all-cause mortality and non-relapse mortality (NRM). Safety will be monitored through adverse event collection and grading per CTCAE 5.0 criteria. Follow-up assessments are scheduled at weeks 1, 2, 3, 4, and months 2, 3, 6, 12 post-transplantation. The study period is from August 2026 to July 2029. Statistical analyses will be performed using SPSS and R, with Kaplan-Meier method for OS, and Cox regression and logistic regression for multivariate analyses.

Inclusion criteria

• Age 18 to 70 years.
• Diagnosis of acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL), with first complete remission (CR1) achieved after induction chemotherapy.
• Classified as non-high-risk per ELN 2022 risk stratification guidelines.
• ECOG performance status ≥ 2 (not due to leukemia) OR Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≥ 2.
• Willing to undergo allogeneic hematopoietic stem cell transplantation and has a suitable donor.
• Voluntarily signs informed consent form after full understanding of the study.

Exclusion criteria

• Allergy to any component of the study drugs.
• Psychiatric or psychological disorders that prevent cooperation with treatment.
• Uncontrolled systemic or local severe infection.
• Severe dysfunction of major organs (heart, lung, liver, kidney) that, in the investigator's opinion, makes the patient unsuitable for enrollment.
• Currently participating in or planning to participate in any other clinical study.
• Any other conditions that, in the investigator's opinion, make the patient unsuitable for enrollment.