Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20230913-00115
Y Y Shen, D L Yang, Y He, A M Pang, X Chen, Q L Ma, R L Zhang, J L Wei, W H Zhai, M Z Han, E L Jiang, S Z Feng
Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.
{"title":"[Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia].","authors":"Y Y Shen, D L Yang, Y He, A M Pang, X Chen, Q L Ma, R L Zhang, J L Wei, W H Zhai, M Z Han, E L Jiang, S Z Feng","doi":"10.3760/cma.j.cn121090-20230913-00115","DOIUrl":"10.3760/cma.j.cn121090-20230913-00115","url":null,"abstract":"<p><p>Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20231127-00283
Y Pu, X Y Zhou, Y Liu, X Kong, J J Han, J Zhang, Z H Lin, J Chen, H Y Qiu, D P Wu
Objective: Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Methods: Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. Results: In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion: BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.
研究目的探索桥接blinatumomab(BiTE)联合嵌合抗原受体T(CAR-T)细胞疗法治疗急性B细胞淋巴细胞白血病(B-ALL)成人患者的有效性和安全性。方法:回顾性分析2018年8月至2023年5月在苏州大学附属第一医院接受治疗的36例成人B-ALL患者的临床数据。共纳入 36 例患者:男性 18 例,女性 18 例。中位年龄为43.5岁(21-72岁)。此外,还报告了21例费城染色体阳性急性淋巴细胞白血病病例,其中16例为复发或难治性病例。18例患者接受了blinatumomab桥接疗法,随后接受了CAR-T细胞疗法,18例患者接受了CAR-T细胞疗法。本研究分析了两组患者的疗效和安全性。研究结果在BiTE桥接至CAR-T组中,16名患者在接受BiTE免疫疗法后获得了完全缓解(CR),CR率为88.9%。桥接 CAR-T 治疗一个月后,骨髓检查显示 CR 率为 100.0%,最小残留病(MRD)阴性率高于非桥接治疗组(94.4% vs. 61.1%,Fisher,P=0.041)。BiTE桥接至CAR-T组细胞因子释放综合征和其他不良反应的发生率低于非桥接疗法组(11.1% vs. 50.0%,Fisher,P=0.027)。随访显示,13 名患者继续保持 MRD 阴性,5 名患者在治疗后 8.40 个月(2.57-10.20 个月)复发。5名复发患者中有2名在接受第二次CAR-T细胞治疗后达到了CR。在非桥接疗法组中,10 名患者保持持续 MRD 阴性,7 名患者复发,6 名患者死亡。BiTE桥接至CAR-T组的1年总生存率高于非桥接治疗组,在0.1水平上差异有统计学意义(88.9%±10.5% vs. 66.7%±10.9%,P=0.091)。结论BiTE桥接CAR-T细胞疗法在成人B-ALL治疗中表现出卓越的疗效,近期复发率较低,并且在随访过程中还将对长期疗效进行评估。
{"title":"[Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia].","authors":"Y Pu, X Y Zhou, Y Liu, X Kong, J J Han, J Zhang, Z H Lin, J Chen, H Y Qiu, D P Wu","doi":"10.3760/cma.j.cn121090-20231127-00283","DOIUrl":"https://doi.org/10.3760/cma.j.cn121090-20231127-00283","url":null,"abstract":"<p><p><b>Objective:</b> Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . <b>Methods:</b> Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. <b>Results:</b> In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% <i>vs</i>. 61.1%, Fisher, <i>P</i>=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% <i>vs</i>. 50.0%, Fisher, <i>P</i>=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% <i>vs</i>. 66.7%±10.9%, <i>P</i>=0.091) . <b>Conclusion:</b> BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-2023915-00121
X W Peng, M Xian, N P Ban, Q Sun
Bone marrow biopsy is one of the important means of hematopathological diagnosis, which has decisive diagnostic significance for various benign and malignant lymphohematopoietic system diseases. Its diagnostic value includes morphological observation, immunohistochemistry, genetics, and molecular biology testing. Owing to the unique nature of bone marrow biopsy, decalcification is an essential step in the pre-treatment process. Its purpose is to remove calcium from bone tissue, preserve intact collagen fiber components, facilitate tissue sectioning, and prevent tissue detachment during staining. If bone marrow biopsy lacks sufficient decalcification, preparing a section is difficult. Conversely, if decalcification is excessive, it can seriously disrupt tissue antigen activity. Therefore, a decalcification method with high decalcification efficiency and mild antigen damage is essential for bone marrow biopsy. This article introduces a bone marrow biopsy tissue decalcification method with high efficiency and less antigen loss: decalcification is performed at room temperature with 12% formic acid and 8% hydrochloric acid decalcification solution on a shaker.
{"title":"[Introduction of a decalcification method for bone marrow biopsy tissue].","authors":"X W Peng, M Xian, N P Ban, Q Sun","doi":"10.3760/cma.j.cn121090-2023915-00121","DOIUrl":"https://doi.org/10.3760/cma.j.cn121090-2023915-00121","url":null,"abstract":"<p><p>Bone marrow biopsy is one of the important means of hematopathological diagnosis, which has decisive diagnostic significance for various benign and malignant lymphohematopoietic system diseases. Its diagnostic value includes morphological observation, immunohistochemistry, genetics, and molecular biology testing. Owing to the unique nature of bone marrow biopsy, decalcification is an essential step in the pre-treatment process. Its purpose is to remove calcium from bone tissue, preserve intact collagen fiber components, facilitate tissue sectioning, and prevent tissue detachment during staining. If bone marrow biopsy lacks sufficient decalcification, preparing a section is difficult. Conversely, if decalcification is excessive, it can seriously disrupt tissue antigen activity. Therefore, a decalcification method with high decalcification efficiency and mild antigen damage is essential for bone marrow biopsy. This article introduces a bone marrow biopsy tissue decalcification method with high efficiency and less antigen loss: decalcification is performed at room temperature with 12% formic acid and 8% hydrochloric acid decalcification solution on a shaker.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20230816-00070
X M Lu, D Y Fu, Y F Zhang, L D Zhao, L Wang, J Yang, J Liu, J W Zheng, L H Yang, G Wang
Objective: The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. Methods: The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot. Results: Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level. Conclusion: The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.
{"title":"[Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene].","authors":"X M Lu, D Y Fu, Y F Zhang, L D Zhao, L Wang, J Yang, J Liu, J W Zheng, L H Yang, G Wang","doi":"10.3760/cma.j.cn121090-20230816-00070","DOIUrl":"10.3760/cma.j.cn121090-20230816-00070","url":null,"abstract":"<p><p><b>Objective:</b> The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. <b>Methods:</b> The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot. <b>Results:</b> Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level. <b>Conclusion:</b> The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20230831-00099
Y Q Sun, Y Fu, O X Ji, L J Wang
The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells (P<0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 µmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines (P<0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level (P<0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells (P<0.05) and a decrease in G2/M-phase cells (P<0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression (P<0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.
{"title":"[Effects of polyphyllin Ⅶ on proliferation, apoptosis and cell cycle of diffuse large B-cell lymphoma cells].","authors":"Y Q Sun, Y Fu, O X Ji, L J Wang","doi":"10.3760/cma.j.cn121090-20230831-00099","DOIUrl":"https://doi.org/10.3760/cma.j.cn121090-20230831-00099","url":null,"abstract":"<p><p>The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells (<i>P</i><0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 µmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines (<i>P</i><0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level (<i>P</i><0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells (<i>P</i><0.05) and a decrease in G2/M-phase cells (<i>P</i><0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression (<i>P</i><0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20231207-00297
Y Xu, J Zhang, S L Xue, M Miao, Y Wang, S N Chen, H Y Qiu, D P Wu
Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, th
研究目的本研究旨在评估吉特替尼(Gilt)为基础的联合疗法对FLT3-ITD(+)R/R急性髓细胞白血病患者进行allo-HSCT桥接治疗的安全性和有效性。此外,研究还旨在评估吉尔特维持治疗对allo-HSCT后患者预后的影响。研究方法回顾性分析2019年8月至2023年1月在苏州大学附属第一医院接受治疗的26例FLT3-ITD(+)R/R AML患者的临床数据。分析包括评估所有入组患者的综合完全缓解率(CRc)、总生存期(OS)时间、无病生存期(DFS)时间和不良事件。研究结果共纳入26例FLT3-ITD(+)R/R急性髓细胞白血病患者,其中男性14例,女性12例,中位年龄为38(18-65)岁。其中18例为难治性,8例为复发。14至21天的疗效评估显示,完全缓解(CR)率为26.9%(7/26),CR伴血液学不完全恢复率为57.7%(15/26),部分反应(PR)率为7.7%(2/26)。CRc为84.6%(22/26),最小残留病(MRD)阴性率为65.4%。所有患者的12个月累积OS率为79.0%,24个月累积OS率为72.0%。中位 OS 时间尚未确定。中位随访时间为 16.0 个月。在对治疗有反应的患者中,12 个月累计 DFS 率为 78.0%,24 个月累计 DFS 率为 71.0%。中位 DFS 时间尚未确定。接受allo-HSCT的患者的中位OS时间明显长于未接受allo-HSCT的患者(3.3个月,95%CI 2.2-4.3个月,P=0.005)。allo-HSCT后接受或未接受吉尔特维持治疗的患者的中位OS时间未确定,但allo-HSCT治疗后接受吉尔特维持治疗的患者的OS时间长于allo-HSCT治疗后未接受吉尔特维持治疗的患者(P=0.019)。本研究中FLT3-ITD突变清除率为38.5%,FLT3-ITD突变清除患者的中位OS时间未确定,但明显长于未清除FLT3-ITD突变患者的中位OS时间(15.0个月;P=0.018)。基于吉尔特的联合疗法最常见的3级及以上血液不良事件包括白细胞减少(76.9%)、中性粒细胞减少(76.9%)、发热性中性粒细胞减少(61.5%)、血小板减少(69.2%)和贫血(57.7%)。一名患者在异体 HSCT 治疗后口服吉尔特维持治疗期间出现了分化综合征,但治疗后病情有所好转。结论基于 Gilt 的联合疗法对治疗 FLT3-ITD(+) R/R AML 非常有效。它具有高CRc、MRD阴性率和快速起效的特点,能显著提高患者的生存率。此外,FLT3-ITD 突变的清除率也很高。此外,在allo-HSCT治疗后实施桥接allo-HSCT和Gilt维持治疗也大大提高了患者的生存率。密切监测和处理治疗过程中可能出现的任何不良事件至关重要。
{"title":"[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation].","authors":"Y Xu, J Zhang, S L Xue, M Miao, Y Wang, S N Chen, H Y Qiu, D P Wu","doi":"10.3760/cma.j.cn121090-20231207-00297","DOIUrl":"10.3760/cma.j.cn121090-20231207-00297","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. <b>Methods:</b> The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. <b>Results:</b> A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%<i>CI</i> 2.2-4.3 months, <i>P</i>=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (<i>P</i>=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; <i>P</i>=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. <b>Conclusion:</b> The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, th","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.121090-20231012-00195
Y Sun, J Jiang, L R Sun, F Y Yan, L Z Wang
{"title":"[PICALM-MLLT10 fusion gene positive with multiple gene mutations in a child with T-lymphoblastic lymphoma/leukemia: a case report].","authors":"Y Sun, J Jiang, L R Sun, F Y Yan, L Z Wang","doi":"10.3760/cma.j.121090-20231012-00195","DOIUrl":"10.3760/cma.j.121090-20231012-00195","url":null,"abstract":"","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20231024-00227
Y F Deng, X L Qian, Y Xu, X Yang, H J Yuan
{"title":"[Bendamustine and tofacitinib treatment of T-cell prolymphocytic leukemia: a case report].","authors":"Y F Deng, X L Qian, Y Xu, X Yang, H J Yuan","doi":"10.3760/cma.j.cn121090-20231024-00227","DOIUrl":"10.3760/cma.j.cn121090-20231024-00227","url":null,"abstract":"","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20231013-00199
Y F Zhao, J M Shi, H R Fu, Y Q Zhao, H Zhou, Y M Zhao
A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.
{"title":"[Allogeneic hematopoietic stem cell transplantation in a patient with MonoMAC syndrome and hematopoietic dysplasia which was induced by GATA2 deficiency: a case report and literature review].","authors":"Y F Zhao, J M Shi, H R Fu, Y Q Zhao, H Zhou, Y M Zhao","doi":"10.3760/cma.j.cn121090-20231013-00199","DOIUrl":"10.3760/cma.j.cn121090-20231013-00199","url":null,"abstract":"<p><p>A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.3760/cma.j.cn121090-20231101-00243
S L Chen, Y Y Shi, L N Zhang, M Gong, X Y Zhang, X L Zhao, M Z Hao, J L Wei, Y He, S Z Feng, M Z Han, E L Jiang
Objective: The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. Methods: A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. Results: Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS (P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS (P=0.001, HR=6.981, 95%CI 2.186-22.300; P=0.010, HR=6.719, 95%CI 1.572-28.711; P=0.026, HR=3.386, 95%CI 1.158-9.901; P=0.006, HR=0.151, 95%CI 0.039-0.581) . Conclusion: For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.
{"title":"[Clinical efficacy of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome-evolved acute myeloid leukemia].","authors":"S L Chen, Y Y Shi, L N Zhang, M Gong, X Y Zhang, X L Zhao, M Z Hao, J L Wei, Y He, S Z Feng, M Z Han, E L Jiang","doi":"10.3760/cma.j.cn121090-20231101-00243","DOIUrl":"https://doi.org/10.3760/cma.j.cn121090-20231101-00243","url":null,"abstract":"<p><p><b>Objective:</b> The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. <b>Methods:</b> A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. <b>Results:</b> Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS (<i>P</i><0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS (<i>P</i>=0.001, <i>HR</i>=6.981, 95%<i>CI</i> 2.186-22.300; <i>P</i>=0.010, <i>HR</i>=6.719, 95%<i>CI</i> 1.572-28.711; <i>P</i>=0.026, <i>HR</i>=3.386, 95%<i>CI</i> 1.158-9.901; <i>P</i>=0.006, <i>HR</i>=0.151, 95%<i>CI</i> 0.039-0.581) . <b>Conclusion:</b> For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.</p>","PeriodicalId":24016,"journal":{"name":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}