维奈克拉联合去甲基化药物治疗髓系肉瘤5例临床疗效及安全性分析

宋宝全; 宗李红; 孔金玉; 孔欣; 张剑; 陈君; 仇惠英

doi:10.13201/j.issn.1004-2806.2024.01.005

维奈克拉联合去甲基化药物治疗髓系肉瘤5例临床疗效及安全性分析

- 1.
  苏州大学附属第一医院血液内科，江苏省血液研究所，国家血液系统疾病临床医学研究中心(江苏苏州，215000)
- 2.
  苏州市永鼎医院
基金项目:
江苏省老年健康科研项目(No：LKM2023015)；苏州市科技发展计划(医学创新应用研究)(No：SKY2022134)

详细信息

通讯作者: 仇惠英，E-mail：qiuhuiying@aliyun.com

中图分类号: R733

收稿日期: 2023-01-04

刊出日期: 2024-01-01

Efficacy and safety of venetoclax and hypomethylating agents in myeloid sarcoma

- 1.
  Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Suzhou, 215000, China
- 2.
  Yongding Hospital of Soochow

More Information

Corresponding author: QIU Huiying, E-mail: qiuhuiying@aliyun.com

Received Date: 04 January 2023

Publish Date: 01 January 2024

摘要

摘要: 目的探讨维奈克拉联合去甲基化药物治疗髓系肉瘤的有效性及安全性。方法纳入5例髓系肉瘤患者，其中初诊患者2例，复发难治患者2例，造血干细胞移植后1例。3例给予维奈克拉联合地西他滨，2例给予维奈克拉联合阿扎胞苷，分析临床疗效及安全性。结果 5例患者治疗后病灶超声影像学消失，4例伴有骨髓侵犯均获得完全缓解，不良反应主要为骨髓抑制。截至随访终止日期，4例患者存活，1例患者后因本病复发死亡。结论维奈克拉联合去甲基化药物治疗髓系肉瘤可取得较好的临床疗效，且无明显不良反应。
- 髓系肉瘤 /
- 维奈克拉 /
- 去甲基化药物 /
- 造血干细胞移植
Abstract: Objective To evaluate the efficacy and safety of venetoclax and hypomethylating agents in the treatment of myeloid sarcoma.Methods The clinical data of 5 patients with myeloid sarcoma treated with venetoclax and hypomethylating agents were retrospectively analyzed, among them one patient was isolated myeloid sarcoma after allogeneic hematopoietic cell transplantation, the others were accompanied by bone marrow involvement.Results All the patients got lesions disappeared, 4 cases with bone marrow invasion achieved complete remission, and the main adverse events were bone marrow suppression. By the end of follow-up, four patients were alive and one patient died of subsequent recurrence.Conclusion The combination of venetoclax and hypomethylating agents can achieve good clinical efficacy in the treatment of myeloid sarcoma, without significant adverse events.
- myeloid sarcoma /
- venetoclax /
- hypomethylating agents /
- hematopoietic stem cell transplantation

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表 1 5例髓系肉瘤患者的基本临床特征

序号	性别	年龄/岁	AML分层(ELN)	突变或融合基因	WBC/(×10⁹/L)	治疗方案	复发难治AML	是否移植	侵犯部位	骨髓侵犯	免疫组织化学结果
1	女	39	高危(M4)	复杂核型	6.83	IA、HAG	是	否	颈部淋巴结	原幼47%	MPO⁺、CD34⁺、C117⁺、BCL2⁺、CD3^-、CD20^-、Ki-67(60%)
2	男	43	低危(M2)	CEBPA双突变	104.00	IAC、中剂量Ara-c、中剂量Ara-c	是	否	肺部	原幼10%	MPO⁺、CD34⁺、CD117⁺、CD3^-、CD20^-、Ki-67(40%~60%)
3	女	40	高危(M5)	FLT3-ITD (AR=0.67)	19.57	IA、索拉非尼+HAA、FA、HSCT	否	是	眼眶内直肌	未累及	MPO⁺、CD34⁺、CD1a^-、CD3^-、CD19^-、CD15^dim、Ki-67(53%)
4	男	45	中危(M5)	阴性	2.20	初诊	否	否	颈部淋巴结	原幼93%	CD45⁺、MPO⁺、CD117⁺、CD34⁺、CD3^-、Ki-67(>70%)
5	女	52	中危(M4)	DNMT3A、IDH2	3.94	初诊	否	否	皮肤	原幼58%	MPO⁺、CD34⁺、BCL2⁺、CD3^-、CD22^-、Ki-67(70%)
IA：去甲氧柔红霉素+阿糖胞苷；HAG：高三尖杉酯碱+阿糖胞苷+粒细胞集落刺激因子；IAC：去甲氧柔红霉素+阿糖胞苷+克拉屈滨；Ara-c：阿糖胞苷；HAA：高三尖杉酯碱+阿克拉霉素+阿糖胞苷；FA：氟达拉滨+阿糖胞苷。

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表 2 5例髓系肉瘤患者的治疗及转归

序号	治疗方案	骨髓评估	髓外表现	后续治疗	随访时间/月	转归(死亡原因)
1	VEN+AZA	MRD阴性	CR	中剂量Ara-c、Haplo-HSCT	10	死亡(复发、感染)
2	VEN+AZA	MRD阴性	CR	VEN+AZA、Haplo-HSCT	12	存活
3	VEN+DAC	未评估	PR	DLI、VEN+DAC、放疗、VEN+DAC、DLI	15	存活
4	VEN+DAC	MRD阴性	CR	DAC+中剂量Ara-c、中剂量Ara-c、DAC	15	存活
5	VEN+DAC	MRD阴性	CR	DAC+中剂量Ara-c、中剂量Ara-c+ 去甲氧柔红霉素、Haplo-HSCT	18	存活

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参考文献(22)

[1]	Solh M, Solomon S, Morris L, et al. Extramedullary acute myelogenous leukemia[J]. Blood Rev, 2016, 30(5): 333-339. doi: 10.1016/j.blre.2016.04.001
[2]	Begna KH, Kittur J, Yui J, et al. De novo isolated myeloid sarcoma: comparative analysis of survival in 19 consecutive cases[J]. Br J Haematol, 2021, 195(3): 413-416. doi: 10.1111/bjh.17742
[3]	Bakst R, Powers A, Yahalom J. Diagnostic and Therapeutic Considerations for Extramedullary Leukemia[J]. Am J Hematol, 2020, 22(7): 75.
[4]	Magdy M, Abdel Karim N, Eldessouki I, et al. Myeloid Sarcoma[J]. Oncol Res Treat, 2019, 42(4): 224-229.
[5]	Cunningham I, Hamele-Bena D, Guo Y, et al. Extramedullary leukemia behaving as solid cancer: clinical, histologic, and genetic clues to chemoresistance in organ sites[J]. Am J Hematol, 2019, 94(11): 1200-1207. doi: 10.1002/ajh.25594
[6]	DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia[J]. N Engl J Med, 2020, 383(7): 617-629. doi: 10.1056/NEJMoa2012971
[7]	杨莉莉, 王淑君, 胡婉贞, 等. 阿扎胞苷联合维奈克拉治疗老年急性髓系白血病患者临床疗效分析[J]. 临床血液学杂志, 2022, 35(7): 512-516, 521. https://lcxy.whuhzzs.com/article/doi/10.13201/j.issn.1004-2806.2022.07.012
[8]	Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial[J]. Blood, 2020, 135(24): 2137-2145. doi: 10.1182/blood.2020004856
[9]	Bakst RL, Tallman MS, Douer D, et al. How I treat extramedullary acute myeloid leukemia[J]. Blood, 2011, 118(14): 3785-3793. doi: 10.1182/blood-2011-04-347229
[10]	Shallis RM, Gale RP, Lazarus HM, et al. Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved[J]. Blood Rev, 2021, 47: 100773. doi: 10.1016/j.blre.2020.100773
[11]	Eckardt JN, Stölzel F, Kunadt D, et al. Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations[J]. J Hematol Oncol, 2022, 15(1): 60. doi: 10.1186/s13045-022-01267-7
[12]	Ramia de Cap M, Wu LP, Pihan GA, et al. NPM1 mutations may be associated with adverse outcome in the setting of myeloid neoplasms with complex karyotype[J]. Leuk Res, 2022, 123: 106965. doi: 10.1016/j.leukres.2022.106965
[13]	Almond LM, Charalampakis M, Ford SJ, et al. Myeloid Sarcoma: Presentation, Diagnosis, and Treatment[J]. Clin Lymphoma Myeloma Leuk, 2017, 17(5): 263-267. doi: 10.1016/j.clml.2017.02.027
[14]	Ye F, Zhang H, Zhang W, et al. Clinical characteristics, pathology features and outcomes of pediatric myeloid sarcoma: A retrospective case series[J]. Front Pediatr, 2022, 10: 927894. doi: 10.3389/fped.2022.927894
[15]	Ball S, Knepper TC, Deutsch YE, et al. Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations[J]. Cancer, 2022, 128(21): 3880-3887. doi: 10.1002/cncr.34459
[16]	Lazzarotto D, Candoni A, Filì C, et al. Clinical outcome of myeloid sarcoma in adult patients and effect of allogeneic stem cell transplantation. Results from a multicenter survey[J]. Leuk Res, 2017, 53: 74-81. doi: 10.1016/j.leukres.2016.12.003
[17]	Zhao H, Dong Z, Wan D, et al. Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma[J]. Sci Rep, 2022, 12(1): 6752. doi: 10.1038/s41598-022-10831-7
[18]	龚敏, 吴迪, 李秋柏, 等. 维奈克拉治疗急性髓系白血病的疗效与安全性的单中心真实世界研究[J]. 临床血液学杂志, 2022, 35(5): 359-363. https://lcxy.whuhzzs.com/article/doi/10.13201/j.issn.1004-2806.2022.05.012
[19]	Stevens B, Pollyea DA. Venetoclax response prediction in acute myeloid leukemia: are we Finnish-ed with uncertainty?[J]. Haematologica, 2023, 108(7): 1715-1717. doi: 10.3324/haematol.2022.282440
[20]	Kuusanmaki H, Kytola S, Vanttinen I, et al. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia[J]. Haematologica, 2023, 108(7): 1768-1781.
[21]	Otoukesh S, Zhang J, Nakamura R, et al. The efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia with extramedullary involvement[J]. Leuk Lymphoma, 2020, 61(8): 2020-2023. doi: 10.1080/10428194.2020.1742908
[22]	Li Y, Dai H, Yao D, et al. Central nervous system relapse of acute promyelocytic leukemia treated by oral Venetoclax with Azacitidine achieved complete remission[J]. Ann Hematol, 2022, 101(8): 1865-1867. doi: 10.1007/s00277-022-04823-w