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Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2655-2663页

作者： Zhi-Min Fan Dao-Lei Wu Neng-Wen Xu Li Ye Li-Ping Yan Lin-Jie Li Jun-Yu Zhang Department of Hematology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina Department of Ophthalmology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina Department of General Practice Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina Department of Pathology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina

BACKGROUND High-grade B-cell lymphoma(HGBL)is an unusual malignancy that includes myelocytomatosis viral oncogene(MYC),B-cell lymphoma-2(BCL-2),and/or BCL-6 rearrangements,termed double-hit or triple-hit lymphomas,and HGBL-not otherwise specific(HGBL-NOS),which are morphologically characteristic of HGBL but lack MYC,BCL-2,or BCL-6 rearrangements.HGBL is partially transformed by follicular lymphoma and other indolent lymphoma,with few cases of marginal zone lymphoma(MZL)transformation.HGBL often has a poor prognosis and intensive therapy is currently mainly advocated,but there is no good treatment for these patients who cannot tolerate chemotherapy.CASE SUMMARY We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression.Gene analysis revealed the gene expression profile was identical in the pre-and post-transformed tissues,suggesting that the two diseases are homologous,not secondary tumors.The chemotherapy was ineffective and the side effect was severe,so we tried combination therapy including venetoclax and obinutuzumab.The patient tolerated treatment well,and reached partial response.The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure.He survived for 12 months after diagnosis.CONCLUSION venetoclax combined with obinutuzumab might improve the survival in some HGBL patients,who are unsuitable for chemotherapy.

关键词： Marginal zone lymphoma High-grade B-cell lymphoma Terminal deoxynucleotidyl transferase venetoclax TP53 mutation Case report

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Clinical Effects of venetoclax in the Treatment of Acute Myeloid Leukemia in the Elderly

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Proceedings of Anticancer Research 2024年第3期8卷 80-83页

作者： Ben Niu Limin Hou Department of Hematology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from January 2022 to January 2024 were selected, including 38 cases of patients whose primary treatment was not suitable for intensive chemotherapy and 12 cases of relapsed/refractory AML patients, to observe the therapeutic efficacy and safety of venetoclax. Results: Among the 38 patients whose primary treatment was not suitable for intensive chemotherapy, 5 cases were treated with venetoclax monotherapy, 33 cases were treated with venetoclax + azacitidine, and 25 patients (65.79%) achieved complete remission (CR) with incomplete hematologic recovery (CRi) after 28 days of treatment;10 patients with relapsed/refractory AML were treated with venetoclax + azacitidine, and 2 patients were treated with venetoclax + azacitidine + chemotherapy, and 2 patients achieved optimal therapeutic response after 28 days of treatment and CR/CRi was achieved in 7 patients (58.33%). There were 47 (94.0%) patients with grade 3 or higher granulocytopenia, 46 (92.0%) patients with hemoglobin reduction, and 43 (86.0%) patients with thrombocytopenia, developed after 28 days of treatment. 11 patients developed infections after treatment and there was one case of tumor lysis syndrome. Conclusion: The response rate of venetoclax monotherapy and combination in elderly AML induction therapy is high, and the overall tolerability of elderly patients is good, so it can be popularized and applied.

关键词： venetoclax Elderly Acute myeloid leukemia Efficacy

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Observation on the Clinical Effect of Applying venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

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Journal of Clinical and Nursing Research 2024年第4期8卷 248-252页

作者： Ben Niu Limin Hou Department of Hematology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

关键词： Acute myeloid leukemia venetoclax Demethylating drugs Combination therapy Efficacy

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高三尖杉酯碱联合venetoclax及阿扎胞苷治疗老年急性髓系白血病的临床研究

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中国处方药 2024年第2期22卷 129-132页

作者：张湘兰李孔扬李志诚阳江市人民医院广东阳江529500

目的评估高三尖杉酯碱联合venetoclax(维奈托克)及阿扎胞苷治疗老年急性髓系白血病(AML)的临床效果。方法选择2021年7月~2023年3月期间收治的不接受强化化疗的老年(≥65岁)AML患者40例为研究对象,随机将其分为试验组(给予高三尖杉酯... 详细信息

目的评估高三尖杉酯碱联合venetoclax(维奈托克)及阿扎胞苷治疗老年急性髓系白血病(AML)的临床效果。方法选择2021年7月~2023年3月期间收治的不接受强化化疗的老年(≥65岁)AML患者40例为研究对象,随机将其分为试验组(给予高三尖杉酯碱联合venetoclax及阿扎胞苷化疗)、对照组(给予venetoclax联合阿扎胞苷化疗),各20例。记录两组老年AML患者临床疗效、化疗第7天肝肾功能、总生存期(OS)、无复发生存期(RFS)、无事件生存期(EFS)及药物毒副作用并进行分析。结果试验组综合完全缓解率以及总有效率均明显高于对照组(P 0.05)。试验组OS、RFS、EFS均明显长于对照组(P 0.05)。结论对老年AML患者给予高三尖杉酯碱联合venetoclax及阿扎胞苷化疗疗效较好,可能会对患者的肝肾功造成一定损害,但可明显延长患者生存时间,安全性较高。

关键词：急性髓系白血病高三尖杉酯碱 venetoclax 阿扎胞苷生存期

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venetoclax resistance:mechanistic insights and future strategies

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Cancer Drug Resistance 2022年第2期5卷 380-400页

作者： Faustine Ong Kunhwa Kim Marina Y.Konopleva Department of Leukemia The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA.

Acute myeloid leukemia(AML)is historically associated with poor prognosis,especially in older AML patients unfit for intensive chemotherapy.The development of venetoclax,a potent oral BH3(BCL-2 homology domain 3)mimetic,has transformed the AML treatment.However,the short duration of response and development of resistance remain major concerns.Understanding mechanisms of resistance is pivotal to devising new strategies and designing rational drug combination regimens.In this review,we will provide a comprehensive summary of the known mechanisms of resistance to venetoclax and discuss venetoclax-based combination therapies.Key contributing factors to venetoclax resistance include dependencies on alternative anti-apoptotic BCL-2 family proteins and selection of the activating kinase mutations.Mutational landscape governing response to venetoclax and strategic approaches developed considering current knowledge of mechanisms of resistance will be addressed.

关键词： venetoclax acute myeloid leukemia hypomethylating agents Azacitidine Decitabine resistance BCL2 protein human

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HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第8期23卷 666-681页

作者： Cancan LUO Tiantian YU Ken H.YOUNG Li Yu Department of Hematology the Second Affiliated Hospital of Nanchang University Nanchang 330006China Jiangxi ProvinceKey Laboratory of Hematology Nanchang 330006 China Department of Hematopathology Duke University School of MedicineDuke University Medical CenterDurhamNC 27710USA

Diffuse large B-cell lymphoma(DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%-15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2(BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL;however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase(HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.

关键词： Diffuse large B-cell lymphoma(DLBCL) Histone deacetylase(HDAC)inhibitor venetoclax MYC BCL2 TP53

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T/myeloid mixed-phenotype acute leukemia treated with venetoclax and decitabine:A case report

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世界临床病例杂志 2023年第26期11卷 6200-6205页

作者： Sungwoo Park Eun Jeong Jeong Jung Hun Kang Gyeong-Won Lee Se-Il Go Dong-Hyun Lee Eun-Ha Koh Division of Hematology and Oncology Department of Internal MedicineGyeongsang National University HospitalGyeongsang National University School of MedicineGyeongsang National UniversityJinju 52727South Korea Department of Internal Medicine Institute of Health SciencesGyeongsang National University Changwon HospitalGyeongsang National University School of MedicineChangwon 52828South Korea Department of Laboratory Medicine Gyeongsang National University HospitalGyeongsang National University School of MedicineGyeongsang National UniversityJinju 52828South Korea

BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.

关键词： Mixed-phenotype acute leukemia venetoclax Decitabine Case report

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venetoclax and low-dose cytarabine induced complete remissionin a patient with high-risk acute myeloid leukemia： a case report

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Frontiers of Medicine 2018年第5期12卷 593-599页

作者： Bingshan Liu Roshni Narurkar Madhura Hanmantgad Wahib Zafar Yongping Song Delong Liu The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital Zhengzhou 450003 China Department of Medicine New York Medical College and Westchester Medical Center Valhalla NY 10595 USA

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.

关键词： venetoclax cytarabine AML leukemia

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venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14):A case report

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World Journal of Clinical Cases 2021年第5期9卷 1175-1183页

作者： Yang Yang Li-Juan Fu Chun-Mei Chen Mei-Wei Hu Department of Hematology The Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310014Zhejiang ProvinceChina

BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

关键词： Relapsed/refractory Primary plasma cell leukemia venetoclax Chidamide Very good partial response Case report

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化疗联合venetoclax桥接异基因造血干细胞移植治疗母细胞性浆细胞样树突细胞肿瘤

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中国实验血液学杂志 2023年第5期31卷 1531-1536页

作者：程平王兰兰王秋香关军周英胡彬冯燕邹亮程辉武汉市第一医院血液科湖北武汉430022 武汉市第一医院皮肤科湖北武汉430022 武汉市第一医院病理科湖北武汉430022

目的:探讨化疗联合venetoclax桥接异基因造血干细胞移植(allo-HSCT)治疗母细胞性浆细胞样树突细胞肿瘤的疗效及安全性。方法:回顾性分析2017年7月至2021年12月在武汉市第一医院血液科行allo-HSCT治疗的3例母细胞性浆细胞样树突细胞肿瘤... 详细信息

目的:探讨化疗联合venetoclax桥接异基因造血干细胞移植(allo-HSCT)治疗母细胞性浆细胞样树突细胞肿瘤的疗效及安全性。方法:回顾性分析2017年7月至2021年12月在武汉市第一医院血液科行allo-HSCT治疗的3例母细胞性浆细胞样树突细胞肿瘤患者的资料。结果:3例患者中男性1例,女性2例,年龄27-52岁。首诊时有典型的皮肤病变,也有以急性白血病为主要特征累及全身。肿瘤细胞特征性的分子标记物CD4、CD56、CD123及CD303均为阳性,均表达Bcl-2。3例患者在初始诱导化疗(1例)或复发、进展(2例)后的化疗中联用venetoclax。2例行allo-HSCT前获得完全缓解,1例部分缓解。预处理均采用不含全身放射治疗的清髓性预处理方案。移植物抗宿主病的预防方案为抗胸腺细胞球蛋白^(+)酶酚酸酯^(+)环孢素/他克莫司±甲氨蝶呤。回输单个核细胞数为(16.73-18.35)×10~8/kg,CD34^(+)细胞数(3.57-4.65)×10~6/kg。Allo-HSCT后(^(+)21至^(+)28 d)3例患者均获得完全缓解,供受者嵌合率100%,无Ⅲ-Ⅳ度移植物抗宿主病。1例于移植后^(+)50 d死亡,2例随访时间分别为28和15个月,仍无病生存。结论:母细胞性浆细胞样树突细胞肿瘤为高度侵袭性恶性肿瘤,总体预后差。化疗联合venetoclax桥接allo-HSCT可能使患者获得长期无病生存甚至治愈。移植后的维持治疗目前仍不清楚。

关键词：母细胞性浆细胞样树状突细胞肿瘤化疗 venetoclax 异基因造血干细胞移植

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