Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.
急性髓性白血病(AML)是造血系统相关疾病中常见的血癌,预后较差。研究表明,长非编码 RNA(lncRNA)与包括 AML 在内的多种疾病的发病机制密切相关。然而,具体的分子机制仍不清楚。因此,本研究旨在探讨lncRNA X非活性特异性转录本(lncRNA XIST)对AML的影响及其机制。为了实现我们的目标,我们进行了一些测试。研究利用实时定量聚合酶链反应(qRT-PCR)检测了lncRNA XIST、miR-142-5p和血小板磷酸果糖激酶(PFKP)同工酶的表达。miR-142-5p与lncRNA XIST和PFKP之间的靶向关系通过皮尔逊相关分析、双荧光素酶报告实验和牵引实验得到了验证。功能实验分析了敲除lncRNA XIST对THP-1和U937细胞的影响和作用机制。与骨髓细胞相比,在AML中,lncRNA XIST和PFKP表达水平上调,miR-142-5p表达水平下调。进一步分析发现,lncRNA XIST与miR-142-5p靶向结合,而PFKP是miR-142-5p的靶基因。敲除lncRNA XIST能显著促进miR-142-5p的表达,从而下调PFKP在THP-1和U937细胞中的表达,同时抑制细胞增殖、细胞活力和细胞周期停滞,增加细胞凋亡。敲除 miR-142-5p 逆转了敲除 lncRNA XIST 对 AML 细胞的功能影响。总之,lncRNA XIST的下调可以通过调控miR-142-5p来影响AML的进展。
{"title":"Effect of lncRNA XIST on acute myeloid leukemia cells via miR-142-5p-PFKP axis.","authors":"Zhaozhi Jiang, Tingting Liu, Youhong Wang, Jiao Li, Lusheng Guo","doi":"10.1080/16078454.2024.2306444","DOIUrl":"10.1080/16078454.2024.2306444","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2306444"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2023-12-14DOI: 10.1080/16078454.2023.2293498
Li Wang, Hui Duan, Hongmei Zuo, Zhongyu Wang, Shuili Jiao, Yanli Liu, Huihui Li, Jie Chen
Objectives: Cognitive-behavioral stress management (CBSM) is an effective psychological intervention to relieve psychological and symptomatic distress. This study aimed to investigate the effect of CBSM in anxiety, depression, and post-traumatic stress disorder (PTSD) in parents of pediatric acute myeloid leukemia (AML) patients.
Methods: Totally, 56 pediatric AML patients and 100 parents were randomized into the CBSM group (28 patients and 49 parents) and the normal control (NC) group (28 patients and 51 parents) to receive corresponding interventions for 10 weeks. The questionnaire scores were assessed at month M0, M1, M3, and M6.
Results: In parents of pediatric AML patients, self-rating anxiety scale score at M1 (p = 0.034), M3 (p = 0.010), and M6 (p = 0.003), as well as anxiety at M3 (p = 0.036) and M6 (p = 0.012) were decreased in the CBSM group versus the NC group. Self-rating depression scale score at M3 (p = 0.022) and M6 (p = 0.002), as well as depression at M6 (p = 0.019) were declined in the CBSM group versus the NC group. Symptom checklist-90 (a psychotic status questionnaire) score at M3 (p = 0.031) and M6 (p = 0.019) were declined in the CBSM group versus the NC group. Regarding PTSD, the impact of the events scale-revised score at M3 (p = 0.044) and M6 (p = 0.010) were decreased in the CBSM group versus the NC group. By subgroup analyses CBSM (versus NC) improved all outcomes in parents with anxiety at M0 and depression at M0 (all p < 0.050), but could not affect the outcomes in parents without anxiety or depression at M0 (all p > 0.050).
Conclusion: CBSM reduces anxiety, depression, and PTSD in parents of pediatric AML patients.
{"title":"Cognitive-behavioral stress management relieves anxiety, depression, and post-traumatic stress disorder in parents of pediatric acute myeloid leukemia patients: a randomized, controlled study.","authors":"Li Wang, Hui Duan, Hongmei Zuo, Zhongyu Wang, Shuili Jiao, Yanli Liu, Huihui Li, Jie Chen","doi":"10.1080/16078454.2023.2293498","DOIUrl":"https://doi.org/10.1080/16078454.2023.2293498","url":null,"abstract":"<p><strong>Objectives: </strong>Cognitive-behavioral stress management (CBSM) is an effective psychological intervention to relieve psychological and symptomatic distress. This study aimed to investigate the effect of CBSM in anxiety, depression, and post-traumatic stress disorder (PTSD) in parents of pediatric acute myeloid leukemia (AML) patients.</p><p><strong>Methods: </strong>Totally, 56 pediatric AML patients and 100 parents were randomized into the CBSM group (28 patients and 49 parents) and the normal control (NC) group (28 patients and 51 parents) to receive corresponding interventions for 10 weeks. The questionnaire scores were assessed at month M0, M1, M3, and M6.</p><p><strong>Results: </strong>In parents of pediatric AML patients, self-rating anxiety scale score at M1 (<i>p </i>= 0.034), M3 (<i>p </i>= 0.010), and M6 (<i>p </i>= 0.003), as well as anxiety at M3 (<i>p </i>= 0.036) and M6 (<i>p </i>= 0.012) were decreased in the CBSM group versus the NC group. Self-rating depression scale score at M3 (<i>p </i>= 0.022) and M6 (<i>p </i>= 0.002), as well as depression at M6 (<i>p </i>= 0.019) were declined in the CBSM group versus the NC group. Symptom checklist-90 (a psychotic status questionnaire) score at M3 (<i>p </i>= 0.031) and M6 (<i>p </i>= 0.019) were declined in the CBSM group versus the NC group. Regarding PTSD, the impact of the events scale-revised score at M3 (<i>p </i>= 0.044) and M6 (<i>p </i>= 0.010) were decreased in the CBSM group versus the NC group. By subgroup analyses CBSM (versus NC) improved all outcomes in parents with anxiety at M0 and depression at M0 (all <i>p </i>< 0.050), but could not affect the outcomes in parents without anxiety or depression at M0 (all <i>p </i>> 0.050).</p><p><strong>Conclusion: </strong>CBSM reduces anxiety, depression, and PTSD in parents of pediatric AML patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2293498"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2023-12-27DOI: 10.1080/16078454.2023.2296809
Abdullah AlZahrani, Nada Alsuhebany, Imran K Tailor, Abdullah M Alrajhi
Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), as a targeted therapy for multiple myeloma (MM) patients. It was initially approved by the United States Food and Drug Administration for the treatment of chronic lymphocytic leukemia in April 2016 and later for acute myeloid leukemia in October 2020. However, venetoclax is used as an off-label in a subset group of relapsed and refractory multiple myeloma (RRMM) patients with the presence of translocation t(11;14). Preclinical and clinical studies have highlighted the potential of venetoclax in the management of MM patients, with a specific focus on t(11;14) as a predictive biomarker for initiating venetoclax-based treatment. Later, several studies in RRMM patients that used venetoclax in combination with dexamethasone or/and proteasome inhibitors have shown promising results, in which management guidelines have included venetoclax as one of the options to treat MM patients. Hence, this review focuses on the use of venetoclax in RRMM, clinical efficacy, safety, dosing strategies, and predictive biomarkers for initiating venetoclax. Additionally, we discuss ongoing studies that are investigating different combination of venetoclax regimens in MM patients.
Venetoclax 是一种抗凋亡蛋白 B 细胞淋巴瘤 2(BCL2)的选择性抑制剂,是多发性骨髓瘤(MM)患者的靶向治疗药物。美国食品和药物管理局最初于2016年4月批准该药用于治疗慢性淋巴细胞白血病,随后于2020年10月批准该药用于治疗急性髓性白血病。然而,venetoclax作为一种标签外药物,被用于存在t(11;14)易位的复发性和难治性多发性骨髓瘤(RRMM)亚组患者。临床前和临床研究强调了 Venetoclax 在治疗 MM 患者方面的潜力,并特别关注 t(11;14)作为启动基于 Venetoclax 治疗的预测性生物标志物的作用。后来,几项针对 RRMM 患者的研究显示,venetoclax 与地塞米松或/和蛋白酶体抑制剂联合使用可取得良好疗效,管理指南已将 venetoclax 作为治疗 MM 患者的备选方案之一。因此,本综述重点探讨了venetoclax在RRMM中的应用、临床疗效、安全性、剂量策略以及启动venetoclax的预测性生物标志物。此外,我们还讨论了正在进行的研究,这些研究正在对 MM 患者进行不同的 venetoclax 方案组合研究。
{"title":"Advancing the understanding of venetoclax in t(11;14)-positive multiple myeloma: a comprehensive review of clinical evidence and future prospects.","authors":"Abdullah AlZahrani, Nada Alsuhebany, Imran K Tailor, Abdullah M Alrajhi","doi":"10.1080/16078454.2023.2296809","DOIUrl":"10.1080/16078454.2023.2296809","url":null,"abstract":"<p><p>Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL2), as a targeted therapy for multiple myeloma (MM) patients. It was initially approved by the United States Food and Drug Administration for the treatment of chronic lymphocytic leukemia in April 2016 and later for acute myeloid leukemia in October 2020. However, venetoclax is used as an off-label in a subset group of relapsed and refractory multiple myeloma (RRMM) patients with the presence of translocation t(11;14). Preclinical and clinical studies have highlighted the potential of venetoclax in the management of MM patients, with a specific focus on t(11;14) as a predictive biomarker for initiating venetoclax-based treatment. Later, several studies in RRMM patients that used venetoclax in combination with dexamethasone or/and proteasome inhibitors have shown promising results, in which management guidelines have included venetoclax as one of the options to treat MM patients. Hence, this review focuses on the use of venetoclax in RRMM, clinical efficacy, safety, dosing strategies, and predictive biomarkers for initiating venetoclax. Additionally, we discuss ongoing studies that are investigating different combination of venetoclax regimens in MM patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2296809"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-12DOI: 10.1080/16078454.2024.2329378
Ying Chen, Zhe Chen, Junjie Cao, Li Lin, Jipeng Li
Objective: Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited.
Methods: In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis.
Results: Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses.
Conclusion: The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.
目的:多发性骨髓瘤(MM由于疾病的异质性,多发性骨髓瘤(MM)的临床表现、对治疗的反应和预后各不相同。有关非移植 MM 患者治疗期间免疫排斥状态与预后之间关系的数据十分有限:我们对 142 名 MM 患者进行了回顾性分析,研究了治疗期间免疫排斥状态与预后之间的关系。所有患者均接受了新型制剂治疗,未进行自体干细胞移植。一种、两种或三种未参与的免疫球蛋白(Igs)低于正常的最低阈值被用来识别免疫反应:结果:治疗期间免疫反应程度越严重的患者,无进展生存期(PFS)和总生存期(OS)越短。46.5%的患者存在严重和持续的免疫抑制(治疗期间至少有两种未涉及的 Igs 持续受到抑制),与治疗期间 Igs 完全或部分恢复正常的患者相比,预后更差。在至少获得完全缓解的患者中,重度和持续免疫反应低下患者的预后较差。此外,根据多变量分析,治疗期间严重和持续的免疫反应是PFS和OS的不良预后因素:结论:治疗期间的免疫排斥程度是非移植骨髓瘤患者生存率的随访指标,非移植骨髓瘤患者严重和持续的免疫排斥可能是预后不良的标志。
{"title":"Severe and continuous immunoparesis during induction or maintenance therapy in nontransplant patients with multiple myeloma is a sign of poor prognosis.","authors":"Ying Chen, Zhe Chen, Junjie Cao, Li Lin, Jipeng Li","doi":"10.1080/16078454.2024.2329378","DOIUrl":"10.1080/16078454.2024.2329378","url":null,"abstract":"<p><strong>Objective: </strong>Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited.</p><p><strong>Methods: </strong>In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis.</p><p><strong>Results: </strong>Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses.</p><p><strong>Conclusion: </strong>The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2329378"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-25DOI: 10.1080/16078454.2024.2331940
Elio Haroun, Seah H Lim, Dibyendu Dutta
Background: Endari (L-glutamine) is a conditional amino acid that reduces the frequency of vaso-occlusive crisis (VOC) in sickle cell disease (SCD).
Aim: To investigate whether Endari could ameliorate intestinal barrier function and improve survival outcomes in SCD.
Methods: We treated female Townes SCD mice with Endari and evaluated their intestinal barrier functions by measuring the recovery of orally administered fluorescein isothiocyanate (FITC)-conjugated dextran 4 kDa in serum, and serum intestinal fatty acid binding proteins (iFABP) and lipopolysaccharide (LPS) concentrations by ELISA. We also explored the impact the Endari has on the survival of the SCD mice that underwent repeated experimentally-induced VOC.
Results: Compared to SCD mice treated with water only, Endari-treated mice showed improved intestinal barrier functions, with decrease in the barrier permeability and reduction in the translocation of lipopolysaccharides from the intestinal lumen into the circulation. These changes occurred after only 4 weeks of Endari treatment. Improved intestinal barrier function was also associated with prolonged survival in Endari-treated SCD mice after repeated experimentally-induced VOC.
Conclusion: Our findings provide the evidence supporting the beneficial effects of Enadri in improving intestinal barrier function and associated survival outcomes in SCD.
{"title":"Endari treatment ameliorates sickle cell-related disruption in intestinal barrier functions and is associated with prolonged survival in sickle cell mice.","authors":"Elio Haroun, Seah H Lim, Dibyendu Dutta","doi":"10.1080/16078454.2024.2331940","DOIUrl":"10.1080/16078454.2024.2331940","url":null,"abstract":"<p><strong>Background: </strong>Endari (L-glutamine) is a conditional amino acid that reduces the frequency of vaso-occlusive crisis (VOC) in sickle cell disease (SCD).</p><p><strong>Aim: </strong>To investigate whether Endari could ameliorate intestinal barrier function and improve survival outcomes in SCD.</p><p><strong>Methods: </strong>We treated female Townes SCD mice with Endari and evaluated their intestinal barrier functions by measuring the recovery of orally administered fluorescein isothiocyanate (FITC)-conjugated dextran 4 kDa in serum, and serum intestinal fatty acid binding proteins (iFABP) and lipopolysaccharide (LPS) concentrations by ELISA. We also explored the impact the Endari has on the survival of the SCD mice that underwent repeated experimentally-induced VOC.</p><p><strong>Results: </strong>Compared to SCD mice treated with water only, Endari-treated mice showed improved intestinal barrier functions, with decrease in the barrier permeability and reduction in the translocation of lipopolysaccharides from the intestinal lumen into the circulation. These changes occurred after only 4 weeks of Endari treatment. Improved intestinal barrier function was also associated with prolonged survival in Endari-treated SCD mice after repeated experimentally-induced VOC.</p><p><strong>Conclusion: </strong>Our findings provide the evidence supporting the beneficial effects of Enadri in improving intestinal barrier function and associated survival outcomes in SCD.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2331940"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-25DOI: 10.1080/16078454.2024.2329027
Maria Agustina Perusini, Claire Andrews, Eshetu G Atenafu, Vikas Gupta, Dawn Maze, Andre C Schuh, Karen Wl Yee, Aniket Bankar, Marta B Davidson, Guillaume Richard-Carpentier, Steven M Chan, Jad Sibai, Aaron D Schimmer, Mark D Minden, Hassan Sibai
This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.
这份回顾性报告介绍了对73名年龄在60岁或以上的费城染色体阴性急性淋巴细胞白血病(Ph阴性ALL)患者进行治疗后观察到的结果和不良事件(AEs),这些患者均接受了结合了聚乙二醇天冬酰胺酶(PEG-ASP)或原生天冬酰胺酶(EC-ASP)的儿科启发方案治疗。值得注意的是,61%的患者出现了严重程度为III-IV级的AEs。最常见的不良反应包括血栓形成(35.6%)、发热性中性粒细胞减少(38.4%)和转氨酶炎(34.2%)。在总生存率、无白血病生存率或早期死亡率方面,AEs 并未转化为显著差异。此外,与之前的数据相比,我们观察到早期死亡率有所下降(11% 对 20%),中位总生存期有所延长(54 个月对 48 个月)。这些研究结果表明,对于年龄较大的噬菌体阴性 ALL 患者来说,使用儿科启发化疗方案 ASP 是一种有效且耐受性良好的治疗选择。不过,这也强调了在整个治疗过程中勤于监测和密切随访的重要性。
{"title":"Outcomes and adverse events in older acute lymphoblastic Leukemia patients treated with a pediatric-inspired protocol with Pegylated or native Asparaginase.","authors":"Maria Agustina Perusini, Claire Andrews, Eshetu G Atenafu, Vikas Gupta, Dawn Maze, Andre C Schuh, Karen Wl Yee, Aniket Bankar, Marta B Davidson, Guillaume Richard-Carpentier, Steven M Chan, Jad Sibai, Aaron D Schimmer, Mark D Minden, Hassan Sibai","doi":"10.1080/16078454.2024.2329027","DOIUrl":"10.1080/16078454.2024.2329027","url":null,"abstract":"<p><p>This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2329027"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To investigate the relationship between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma.
Methods: A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014-2021. All patients underwent PET/CT before treatment and were divided into a training cohort (n = 75) and a validation cohort (n = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve.
Results: Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility.
Conclusion: The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.
{"title":"Construction and validation of an <sup>18</sup>F-FDG-PET/CT-based prognostic model to predict progression-free survival in newly diagnosed multiple myeloma patients.","authors":"Xiaoqing Dong, Ruoyi Wang, Xiuhua Ying, Jiaxuan Xu, Jie Yan, Peipei Xu, Yue Peng, Bing Chen","doi":"10.1080/16078454.2024.2329029","DOIUrl":"10.1080/16078454.2024.2329029","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the relationship between <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma.</p><p><strong>Methods: </strong>A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014-2021. All patients underwent PET/CT before treatment and were divided into a training cohort (<i>n</i> = 75) and a validation cohort (<i>n</i> = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve.</p><p><strong>Results: </strong>Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility.</p><p><strong>Conclusion: </strong>The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2329029"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen.
Methods: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively.
Results: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P < 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, P = 0.003).In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (P > 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290).
Conclusions: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.
研究目的本研究旨在比较venetoclax和低甲基化药物联合疗法与HAG疗法的有效性:我们研究了52例新诊断的急性髓细胞性白血病患者和26例复发难治性急性髓细胞性白血病患者(包括与治疗相关的急性髓细胞性白血病患者和ELN不良风险疾病患者(n = 50))。这些患者分别接受了 Venetoclax 和低甲基化药物及 HAG 方案治疗:29名新确诊的急性髓性白血病患者接受了VEN-HMA(venetoclax-低甲基化药物)治疗,23名患者接受了HAG治疗。VEN-HMA 组的中位年龄为 70 岁,而 HAG 组的中位年龄为 69 岁。在复发和难治性急性髓性白血病患者中,VEN-HMA治疗组有43.8%的患者获得完全缓解(82.7%),与HAG治疗组的50%相近(P > 0.99)。VEN-HMA组和HAG组的中位总生存期相似,分别为4个月和3.67个月(P = 0.290):总之,我们的分析表明,对于新诊断的急性髓细胞性白血病患者,与HAG相比,VEN-HMA的治疗效果更好,完全缓解率和总生存率更高。在复发/难治性急性髓细胞白血病患者中,两种治疗方法的疗效没有显著差异,因此有必要进行样本量更大的进一步研究。
{"title":"The efficacy of the combination of venetoclax and hypomethylating agents versus HAG agents in patients with acute myeloid leukemia: a retrospective study.","authors":"Fei Xin, Yan-Hui Yu, Xu-Liang Shen, Guo-Xiang Zhang","doi":"10.1080/16078454.2024.2350319","DOIUrl":"10.1080/16078454.2024.2350319","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen.</p><p><strong>Methods: </strong>We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively.</p><p><strong>Results: </strong>Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (<i>P </i>< 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, <i>P </i>= 0.003).In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (<i>P </i>> 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (<i>P </i>= 0.290).</p><p><strong>Conclusions: </strong>In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2350319"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aims to investigate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.
Methods: This retrospective analysis included 16 patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation between 2016 and 2022. Among them, 8 patients received HBOT in addition to conventional treatment, while the other 8 received only conventional treatment. The clinical efficacy and safety of HBOT were evaluated by comparing the Numeric Rating Scale pain scores and clinical grades of hematuria before and after treatment, reflecting the patients' urinary pain and hematuria status.
Results: The patients were divided into two groups based on whether they received HBOT. The group that received HBOT (n = 8) had a shorter duration of illness compared to the non-HBOT group (n = 8) (p < 0.05). The time for the NRS to decrease to below 2 was also shorter in the HBOT group. Furthermore, the patients who received HBOT did not experience any significant adverse reactions.
Conclusion: The combination of conventional treatment and hyperbaric oxygen therapy (HBOT) has been shown to improve symptoms such as urinary pain, frequency, urgency, and hematuria in patients with late-onset hemorrhagic cystitis after transplantation. This approach has been proven to be safe and effective.
{"title":"Hyperbaric oxygen therapy improves the efficacy of conventional supportive treatment for late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.","authors":"Yiwen Qu, Peng Zhao, Xiaojie Ding, Xiansen Qiao, Ling Wang, Ying Li","doi":"10.1080/16078454.2024.2356307","DOIUrl":"https://doi.org/10.1080/16078454.2024.2356307","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.</p><p><strong>Methods: </strong>This retrospective analysis included 16 patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation between 2016 and 2022. Among them, 8 patients received HBOT in addition to conventional treatment, while the other 8 received only conventional treatment. The clinical efficacy and safety of HBOT were evaluated by comparing the Numeric Rating Scale pain scores and clinical grades of hematuria before and after treatment, reflecting the patients' urinary pain and hematuria status.</p><p><strong>Results: </strong>The patients were divided into two groups based on whether they received HBOT. The group that received HBOT (<i>n</i> = 8) had a shorter duration of illness compared to the non-HBOT group (<i>n</i> = 8) (<i>p</i> < 0.05). The time for the NRS to decrease to below 2 was also shorter in the HBOT group. Furthermore, the patients who received HBOT did not experience any significant adverse reactions.</p><p><strong>Conclusion: </strong>The combination of conventional treatment and hyperbaric oxygen therapy (HBOT) has been shown to improve symptoms such as urinary pain, frequency, urgency, and hematuria in patients with late-onset hemorrhagic cystitis after transplantation. This approach has been proven to be safe and effective.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2356307"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}