Acute myeloid leukemia (AML) represents the most prevalent form of acute leukemia among adult patients, often associated with dismal prognoses. The latest epidemiological data indicate that approximately 22,010 new cases of AML are diagnosed each year, with 11,090 patients dying from this leukemia subtype in the United States (Siegel et al., 2025). In China, there are 38,571 new AML cases annually, and 20,613 patients succumb to the disease each year (Fu et al., 2025). Over the past decade, significant advancements have been made in improving AML outcomes, driven by the advent of novel targeted agents, cellular and molecular immunotherapies, optimized treatment strategies, and expanded access to hematopoietic stem cell transplantation (HSCT) (DiNardo et al., 2020; Erba et al., 2023; Lu et al., 2025; Zhang et al., 2021). However, the majority of patients still eventually experience disease relapse, and enduring survival remains suboptimal. Therefore, sustaining persistent remission and reducing the risk of relapse continue to be critical challenges. Maintenance therapy (MT) has emerged as a promising approach to achieve more durable remissions and enhance overall survival, yet its optimal application remains to be clearly established (Goulart et al., 2025; Senapati et al., 2023). The objective of MT is to eradicate residual leukemia cells, with treatment options encompassing chemotherapeutic agents, hypomethylating drugs, immunotherapies, and targeted therapies (Oran et al., 2020; Reville et al., 2021; Xuan et al., 2020). Repeated chemotherapy inevitably results in damage to normal tissues and cumulative toxicities. While decitabine and post-transplant low-dose azacitidine have been investigated as maintenance agents, neither has consistently shown a significant improvement in patient survival (Oran et al., 2020; Blum et al., 2017; Foran et al., 2019). The immune checkpoint inhibitors theoretically hold efficacy in inducing anti-leukemia effects. However, the precise role of these agents in AML MT remains unclear, especially considering the potential toxicities they may present (Reville et al., 2021; Liu et al., 2022). Molecular targeted therapy has also been investigated as a maintenance strategy for AML with specific genetic alterations. Posttransplant maintenance using the multikinase inhibitor sorafenib has been shown to improve both relapse-free survival (RFS) and overall survival (OS) in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (Xuan et al., 2020; Burchert et al., 2020). The first- and second-generation FLT3 inhibitors, midostaurin and gilteritinib, failed to yield additional improvements when used as MT in patients who underwent allo-HSCT (Maziarz et al., 2021; Levis et al., 2024). Notably, quizartinib may offer prominent benefit as post-remission maintenance for patients who did not receive consolidative allo-HSCT (Goulart et al., 2025). Trials evaluating IDH1/2 inhibitors, enasidenib and ivosidenib, in the posttransplant setting have demonstrated favorable tolerability and feasibility, with generally promising outcomes in terms of relapse and survival (Fathi et al., 2022; Fathi et al., 2023). Nevertheless, additional studies are still warranted.

China boasts a vast territory and faces imbalances in economic development and certain regional disparities in its healthcare system (Chen and Jin, 2022). These factors lead to poor accessibility to newly emerged therapeutic drugs or render them unaffordable due to economic constraints in a substantial proportion of patients with AML. Therefore, exploring ways to optimize currently accessible treatment approaches and generate more research evidence holds significant guiding value for improving clinical patient management and enhancing long-term prognosis. Randomized controlled trials (RCTs) are regarded as the “gold standard” for evaluating therapeutic efficacy. However, their results are constrained by strict inclusion and exclusion criteria. In contrast, real-world studies (RWSs), by reflecting actual clinical practice, enhance the practicality and generalizability of research findings, and they hold irreplaceable advantages particularly in personalized medicine, long-term efficacy assessment, and public health decision-making (Dang, 2023). Furthermore, the doses of consolidation therapy are relatively insufficient due to constitutional factors Chinese populations, medical conditions, and the incidence of comorbidities of patients with AML in many centers of China. Thus, the present study evaluates decitabine or conventional chemotherapy in MT in a real-world cohort of patients with AML. The results of this study may provide beneficial references for management of AML patients.

The present real-world cohort study evaluated the efficacy and safety of MT with decitabine versus conventional chemotherapy in patients with AML who had achieved remission after induction and consolidation therapy. The results demonstrate that MT significantly improves RFS and OS in this population, with decitabine demonstrating better tolerability and subgroup-specific survival benefits. These findings may provide valuable insights into optimizing maintenance strategies for AML patients in clinical practice.

Our data demonstrate that MT, whether with decitabine or conventional chemotherapy, consistently reduces relapse risk and improves survival compared to no maintenance, aligning with growing evidence supporting its role in post-remission care (Karakus et al., 2022; Senapati et al., 2022). This is particularly relevant in real-world settings, where patients often face barriers to intensive consolidation (e.g., dose-limiting toxicities, comorbidities, or limited access to high-dose regimens), making MT a critical bridge to sustained remission. Notably, the benefits of maintenance were observed across diverse patient subgroups, independent of ELN risk category, MRD status after two courses, or the number of HiDAC consolidation cycles. This universality underscores MT as a foundational strategy to consolidate remission, even in patients with suboptimal responses to initial therapy. A key finding of this study is the pronounced benefit of MT in cytogenetic or ELN intermediate-risk patients. This subgroup, which was associated with inferior outcomes compared to low-risk patients but without the aggressive trajectory of high-risk disease, often faces an “intermediate” prognosis that is difficult to optimize (Shimony et al., 2025). Our data show that MT narrows this gap: intermediate-risk patients receiving maintenance achieved survival outcomes comparable to low-risk patients without maintenance. This suggests that maintenance can effectively mitigate the adverse prognostic impact of intermediate-risk cytogenetics, offering a practical strategy to “upgrade” outcomes in this vulnerable population. Equally compelling is the observation that MT ameliorates the poor prognosis of MRD-positive patients after two courses of therapy. MRD positivity is a well-established marker of residual disease and a strong predictor of relapse (Heuser et al., 2021; van Weelderen et al., 2023). In our cohort, MRD-positive patients receiving maintenance achieved survival comparable to MRD-negative patients without maintenance, indicating that maintenance can suppress residual leukemia cells and “rescue” outcomes in those with persistent disease. This supports the use of maintenance as a targeted intervention for MRD-positive patients, particularly in settings where more intensive interventions (e.g., allo-HSCT) are not feasible. Intriguingly, decitabine showed distinct advantages in patients who received 3–4 cycles of HiDAC consolidation. The superiority of decitabine in this context may stem from its mechanism of direct anti-leukemia and immunomodulatory effects, which was reported to activate dendritic cells (Kwon et al., 2020), reinforce CD8⁺ T cell function (Liu et al., 2023), and promote the maintenance of effector function and memory phenotype of T cells (Kang et al., 2022). This profile makes it particularly well-suited for patients who have completed HiDAC consolidation, as it minimizes the risk of cumulative toxicity while sustaining anti-leukemic activity. It should be noted that the majority of patients (95.5%) in this study were younger than 60 years. Existing evidence has already shown that such a patient subgroup (aged <60 years) failed to benefit from decitabine maintenance (Blum et al., 2017). The difference may derive from relatively lower doses of HiDAC (not all patients received 3 g/m² cytarabine) used in the present study due to constitutional factors, medical conditions, and the occurrence of comorbidities. For such patients, decitabine represents a tolerable and effective long-term maintenance option, reducing the burden of treatment-related complications that often limit adherence in real-world settings. Moreover, decitabine MT yields an OS of approximately 50.0%–68.0% among non-transplant AML patients (Blum et al., 2017; Liu et al., 2022), which is somewhat lower than the 78.2% survival rate observed in the present study. This discrepancy may stem from the distinct genetic backgrounds of the patient cohorts (with 7% vs. 2.0% of patients harboring high-risk cytogenetics in this study) and the limited sample size. Therefore, further investigations with larger patient cohorts are warranted to clarify this issue and validate the aforementioned findings.

Not all subgroups benefited equally from MT. Cytogenetic low-risk patients showed no significant improvement with maintenance, consistent with their favorable prognosis following standard consolidation (Shimony et al., 2025). This suggests that low-risk patients may be overtreated with maintenance, and resources could be redirected to higher-risk groups. Likewise, FLT3-ITD-mutated patients derived no benefit from either of the maintenance strategies evaluated here. FLT3-ITD mutations drive leukemogenesis and confer resistance to conventional therapy (Zalpoor et al., 2022; Tang et al., 2024). The ineffectiveness of decitabine or chemotherapy in this subgroup highlights the need for FLT3 inhibitors (e.g., midostaurin, gilteritinib) as maintenance agents in FLT3-ITD-positive AML, a strategy supported by clinical trials showing reduced relapse risk with FLT3 inhibitor maintenance (Stone et al., 2017). Unfortunately, this study did not include these targeted agents, reflecting the limitations in accessibility to novel small-molecule drugs in real-world settings.

This study has several limitations. First, its retrospective design, small sample size, and certain variations in chemotherapy maintenance regimens may introduce selection bias, particularly in the non-random assignment of maintenance regimens. Second, the cohort lacks data on recently approved agents, such as FLT3 inhibitors and BCL-2 inhibitors (venetoclax), which have transformed AML therapy (Garcia et al., 2024). Integrating these agents into maintenance strategies, either alone or in combination with HMAs, warrants investigation in future prospective studies. Third, the homogeneous nature of a single-center cohort may limit generalizability, especially given regional disparities in AML management across China. Multi-center, prospective trials are needed to validate these findings in diverse populations. Finally, long-term follow-up beyond 5 years is required to assess the durability of maintenance benefits, particularly in certain subgroups.

In conclusion, this real-world study reinforces the value of MT in AML, with particular benefits in intermediate-risk and MRD-positive patients. Decitabine emerges as a superior option for patients who have completed adequate HiDAC consolidation, offering better tolerability and survival gains. For low-risk patients, maintenance may be unnecessary, while FLT3-ITD-mutated patients require alternative strategies, such as FLT3 inhibitors. These findings provide actionable insights to personalize MT, addressing unmet needs in resource-constrained settings and emphasizing the need for broader access to targeted agents in future practice.