Application of prophylactic or pre-emptive therapy after allogeneic transplantation for high-risk patients with t(8;21) acute myeloid leukemia

ABSTRACT

Objectives

To determine the impact of pretransplant measurable residual disease (pre-MRD) and the efficacy of maintenance therapy in t(8;21) acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (allo-HCT).

Methods

We retrospectively analyzed 100 t(8;21) AML patients who underwent allo-HCT between 2013 and 2022. 40 patients received pre-emptive therapy including immunosuppressant adjustment, azacitidine, and donor lymphocyte infusion (DLI) combined with chemotherapy. 23 patients received prophylactic therapy, including azacitidine or chidamide.

Results

Patients with a positive pre-MRD (pre-MRDpos) had a higher 3-year cumulative incidence of relapse (CIR) (25.90% [95% CI, 13.87%–39.70%] vs 5.00% [95% CI, 0.88%–15.01%]; P = 0.008). Pre-MRDpos patients were less likely to have a superior 3-year disease-free survival (DFS) (40.83% [95% CI, 20.80%–80.16%]) if their MRD was still positive at 28 days after transplantation (post-MRD₂₈pos). The 3-year DFS and CIR were 53.17% (95% CI, 38.31% – 73.80%) and 34.87% (95% CI, 18.84% – 51.44%), respectively, for patients receiving pre-emptive interventions after molecular relapse. The 3-year DFS and CIR were 90.00% (95%CI, 77.77% – 100%) and 5.00% (95%CI, 0.31% – 21.10%), respectively, for high-risk patients receiving prophylactic therapy. In most patients, epigenetic-drug-induced adverse events were reversible with dose adjustment or temporary discontinuation.

Conclusion

Patients with pre-MRDpos and post-MRD₂₈pos were more likely to have higher rates of relapse and inferior DFS, even after receiving pre-emptive interventions. Prophylactic therapy may be a better option for high-risk t(8;21) AML patients; however, this warrants further investigation.

KEYWORDS:

• RUNX1-RUNX1T1
• acute myeloid leukemia
• hematopoietic stem cell transplantation
• measurable residual disease
• maintenance therapy

Acknowledgments and fundings

The study was supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund (No. HH22KYZX0034), the National Nature Science Foundation of China (No. 82170217, No. 82070192 and No. 81670171), Fundamental Research Funds for the central universities (No. 3332020052), CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-073), and Key Project of Tianjin Natural Science Foundation (No. 20JCZDJC00410).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The raw data of this article can be available by all authors.

Additional information

Funding

This work was supported by Fundamental Research Funds for the Central Universities: [Grant Number 3332020052]; National Natural Science Foundation of China: [Grant Number 82070192]; CAMS Innovation Fund for Medical Sciences: [Grant Number 2021-I2M-1-073]; Key Project of Tianjin Natural Science Foundation: [Grant Number 20JCZDJC00410]; Haihe Laboratory of Cell Ecosystem Innovation Fund: [Grant Number HH22KYZX0034]; National Nature Science Foundation of China: [Grant Number 82170217].