Abstract: Objective To investigate the clinical and genetic factors influencing hematologic recovery in newly diagnosed, elderly, and unfit patients with acute myeloid leukemia(AML)who have achieved bone marrow remission following treatment with the Venetoclax and Azacitidine combination regimen(VA regimen), thereby providing a basis for individualized clinical treatment. Methods This retrospective analysis examined 61 elderly patients with newly diagnosed AML who presented to the Department of Hematology at Qilu Hospital of Shandong University between April 2020 and October 2025. The cohort consisted of 33 males and 28 females. All patients were treated using the VA regimen; based on the 2022 European leukemia net(ELN)response criteria for AML, those who achieved marrow remission were categorized into either the complete remission(CR)group(n=29)or the complete remission with incomplete hematologic recovery(CRi)group(n=32). Clinical and genetic characteristics of the two groups were compared, and logistic regression was used to screen for independent risk factors for incomplete hematologic remission. Persistent incomplete hematologic recovery was defined as CRi after the first treatment cycle with continued CRi after the second treatment cycle. Among the 32 CRi patients, they were divided into a CR conversion group(n=13)and a persistent hematologic non-remission group(n=16)based on the efficacy of the second cycle. The differences in the distribution of risk factors between the two groups were further compared. Results Multivariate logistic regression analysis showed that myelofibrosis≥2, high-risk stratification of ELN, and TP53 mutation were independent risk factors for CRi(OR=5.75, 95%CI:1.24-41.57, P=0.041; OR=8.57, 95%CI:1.92-61.25, P=0.011; OR=9.33, 95%CI:1.55-179.60, P=0.042, respctively). A total of 13 CRi patients(40.63%)converted to CR in the second cycle, and 11 of them(84.6%)maintained CR in the third cycle; 16(50.00%)of the CRi patients remained in hematologic non-remission. Furthermore, the proportion of patients with myelofibrosis≥ 2 and TP53 mutations was significantly higher in the group with persistent hematologic non-remission. Conclusion In newly diagnosed elderly AML patients receiving VA regimens, hematological recovery is significantly influenced by the degree of myelofibrosis, ELN stratification, and TP53 mutation. Among these, myelofibrosis≥2 and TP53 mutation are the core independent risk factors for incomplete hematological recovery. Some CRi patients can achieve remission by extending the treatment cycle, but patients with moderate to severe fibrosis are more likely to experience persistent non-remission, requiring individualized clinical monitoring and intervention.

Key words: Acute myeloid leukemia, Venetoclax, Azacitidine, Poor hematologic recovery, Risk factors