初诊老年不适合强化疗急性髓系白血病维奈克拉联合阿扎胞苷治疗后血液学恢复不良的危险因素

doi:10.6040/j.issn.1671-7554.0.2026.0349

摘要/Abstract

摘要： 目的探讨维奈克拉联合阿扎胞苷方案(简称VA方案)治疗初诊老年不适合强化疗急性髓系白血病(acute myeloid leukemia, AML)患者获得骨髓缓解后,影响其血液学恢复的临床及遗传学因素,为临床个体化治疗提供依据。方法回顾性分析2020年4月至2025年10月山东大学齐鲁医院血液科初诊老年AML患者 61 例,其中男33例,女28例,60~81(67.9)岁;均采用 VA 方案治疗,根据2022版欧洲白血病网(European leukemia net, ELN)AML疗效评估标准将治疗后达骨髓缓解患者,分为完全缓解(complete remission, CR)组(n=29)和骨髓缓解伴血液学不完全恢复(complete remission with incomplete hematologic recovery, CRi)组(n=32);比较两组临床及基因特征,采用logistic回归分析CRi的独立危险因素。将1周期CRi且2周期仍为CRi定义为持续血液学不缓解,CRi组根据第2周期疗效分为转为CR组(n=13)和持续血液学不缓解组(n=16),进一步比较两组危险因素分布差异。结果多因素logistic回归分析显示,骨髓纤维化≥2级、ELN中高危分层、TP53突变是发生 CRi 的独立危险因素(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)。13例(40.63%)CRi 患者在第2周期转为CR且其中11例(84.6%)可维持,16例(50.00%)CRi 患者持续血液学不缓解,且持续血液学不缓解组中骨髓纤维化≥2级、TP53突变占比增高。结论接受VA方案治疗的初诊老年AML患者,其血液学恢复受骨髓纤维化程度、ELN分层和TP53突变影响。其中骨髓纤维化≥2级和TP53突变是导致血液学不完全恢复的核心独立危险因素。部分 CRi 患者可通过延长治疗周期实现缓解,但中重度纤维化患者更易出现持续不缓解,临床需个体化监测与干预。

关键词: 急性髓系白血病, 维奈克拉, 阿扎胞苷, 血液学恢复不良, 危险因素

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

中图分类号:

R733.71

吕高钰,薛美娟,徐俊杰,刘亚楠,张晴阳,侯明,石艳. 初诊老年不适合强化疗急性髓系白血病维奈克拉联合阿扎胞苷治疗后血液学恢复不良的危险因素[J]. 山东大学学报 (医学版), 2026, 64(8): 56-63.

LYU Gaoyu, XUE Meijuan, XU Junjie, LIU Yanan, ZHANG Qingyang, HOU Ming, SHI Yan. Risk factors for poor hematological recovery after treatment with Venetoclax plus Azacitidine in newly diagnosed elderly patients with unfit-AML[J]. Journal of Shandong University (Health Sciences), 2026, 64(8): 56-63.

参考文献

[1] Kantarjian H M, DiNardo C D, Kadia T M, et al. Acute myeloid leukemia management and research in 2025[J]. CA Cancer J Clin, 2025, 75(1): 46-67.
[2] Döhner H, Wei A H, Appelbaum F R, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN[J]. Blood, 2022, 140(12): 1345-1377.
[3] Löwenberg B, Ossenkoppele G J, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia[J]. N Engl J Med, 2009, 361(13): 1235-1248.
[4] Fernandez H F, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia[J]. N Engl J Med, 2009, 361(13): 1249-1259.
[5] Sasaki K, Ravandi F, Kadia T M, et al. De novo acute myeloid leukemia: a population-based study of outcome in the United States based on the Surveillance, Epidemio-logy, and End Results(SEER)database, 1980 to 2017[J]. Cancer, 2021, 127(12): 2049-2061.
[6] Kantarjian H, Kadia T, DiNardo C, et al. Acute myeloid leukemia: current progress and future directions[J]. Blood Cancer J, 2021, 11(2): 41. DOI:10.1038/s41408-021-00425-3
[7] DiNardo C D, Jonas B A, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia[J]. N Engl J Med, 2020, 383(7): 617-629.
[8] Chua C C, Loo S, Fong C Y, et al. Final analysis of the phase 1b chemotherapy and venetoclax in elderly acute myeloid leukemia trial(CAVEAT)[J]. Blood Adv, 2025, 9(8): 1827-1835.
[9] Çiftçiler R, Haznedaro glu(·overI)C, Sayınalp N, et al. The impact of early versus late platelet and neutrophil recovery after induction chemotherapy on survival outcomes of patients with acute myeloid leukemia[J]. Turk J Haematol, 2020, 37(2): 116-120.
[10] 中华医学会血液学分会白血病淋巴瘤学组. 成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2023年版)[J]. 中华血液学杂志, 2023, 44(9): 705-712. Leukemia & Lymphoma Group, Chinese Society of Hematology, Chinese Medical Association. Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia(non-acute promyelocytic leukemia)(2023 edition)[J]. Chinese Journal of Hematology, 2023, 44(9): 705-712.
[11] Agarwal S K, DiNardo C D, Potluri J, et al. Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments[J]. Clin Ther, 2017, 39(2): 359-367.
[12] Arber D A, Orazi A, Hasserjian R P, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data[J]. Blood, 2022, 140(11): 1200-1228.
[13] Urrutia S, Kantarjian H M, Ravandi-Kashani F, et al. Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis[J]. J Hematol Oncol, 2024, 17(1): 112. DOI: 10.1186/s13045-024-01627-7
[14] Jain A G, Volpe V O, Wang C, et al. Outcomes by best response with hypomethylating agent plus venetoclax in adults with previously untreated acute myeloid leukemia[J]. Ann Hematol, 2025, 104(1): 307-315.
[15] Abou Zahr A, Salama M E, Carreau N, et al. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies[J]. Haematologica, 2016, 101(6): 660-671.
[16] Yao J C, Oetjen K A, Wang T J, et al. TGF-β signaling in myeloproliferative neoplasms contributes to myelofibrosis without disrupting the hematopoietic niche[J]. J Clin Invest, 2022, 132(11): e154092. DOI: 10.1172/JCI154092
[17] Hwang J, Kim H N, Kwon J A, et al. Impact of TP53 mutation on genetic and cellular hierarchy profile in complex karyotype AML/MDS with increased blasts[J]. Blood Cancer J, 2024, 14(1): 201. DOI: 10.1038/s41408-024-01188-3
[18] Liu Y, Elf S E, Miyata Y, et al. p53 regulates hematopoietic stem cell quiescence[J]. Cell Stem Cell, 2009, 4(1): 37-48.
[19] Asai T, Liu Y, Bae N, et al. The p53 tumor suppressor protein regulates hematopoietic stem cell fate[J]. J Cell Physiol, 2011, 226(9): 2215-2221.
[20] Cho H J, Lee J, Yoon S R, et al. Regulation of hematopoietic stem cell fate and malignancy[J]. Int J Mol Sci, 2020, 21(13): 4780. DOI: 10.3390/ijms21134780
[21] Kirschner K, Chandra T, Kiselev V, et al. Proliferation drives aging-related functional decline in a subpopulation of the hematopoietic stem cell compartment[J]. Cell Rep, 2017, 19(8): 1503-1511.
[22] Menendez-Gonzalez J B, Vukovic M, Abdelfattah A, et al. Gata2 as a crucial regulator of stem cells in adult hematopoiesis and acute myeloid leukemia[J]. Stem Cell Reports, 2019, 13(2): 291-306.
[23] Peters I J A, de Pater E, Zhang W. The role of GATA2 in adult hematopoiesis and cell fate determination[J]. Front Cell Dev Biol, 2023, 11:1250827. DOI: 10.3389/fcell.2023.1250827
[24] Sportoletti P, Sorcini D, Falini B. BCOR gene alterations in hematologic diseases[J]. Blood, 2021, 138(24): 2455-2468.
[25] 陈家祺, 耿英华. 以维奈克拉为基础的联合治疗在急性髓系白血病中的研究进展[J]. 中国实验血液学杂志, 2026, 34(2): 600-604. Chen Jiaqi, Geng Yinghua. Research progress of venetoclax-based combination therapy in acute myeloid leukemia[J]. Journal of Experimental Hematology, 2026, 34(2): 600-604.
[26] 战榕. Bcl-2抑制剂在急性髓系白血病中的研究进展:第62届美国血液学年会报道[J]. 临床血液学杂志, 2021, 34(5): 298-301. Zhan Rong. Research progress of Bcl-2 inhibitors in acute myeloid leukemia: report from the 62nd American Society of Hematology annual meeting[J]. Journal of Clinical Hematology, 2021, 34(5): 298-301.
[27] Wang H, Wang X, Shi T, et al. Granulocyte colony-stimulating factor plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia: a multicenter phase 2 trial[J]. Blood Cancer J, 2025, 15(1): 184. DOI: 10.1038/s41408-025-01389-4
[28] Goto T, Numata H, Katsuoka Y, et al. Real-world experience with venetoclax treatment for newly-diagnosed acute myeloid leukemia in Japan(VENUS study): an interim analysis focusing on neutropenia management[J]. Oncol Ther, 2025, 13(2): 519-527.

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