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":null,"pages":null},"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}
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":null,"pages":null},"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":null,"pages":null},"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}
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":null,"pages":null},"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":null,"pages":null},"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}
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":null,"pages":null},"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}
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":null,"pages":null},"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}
Pub Date : 2024-12-01Epub Date: 2024-05-31DOI: 10.1080/16078454.2024.2352686
Anping Xu, Tong Guo, Shuping Zhang, Houlong Luo, Mengxue Shen, Yinghui Ye, Ling Ji
Background: Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population.
Methods: This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein.
Results: A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08-1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04-2.50). The prevalence of MGUS was significantly higher in males than in females (P < 0.05). The median concentration of M-protein was 3.1 g/L, ranging from 0.5 g/L to 25.1 g/L. The M-protein type was IgG in 55.4% of MGUS patients, followed by IgA (31.1%), IgM (9.5%), IgD (0.5%), biclonal (2.3%), and light chain (1.2%). Abnormalities in SPE, FLC ratios, and immunoglobulin levels were observed in 78.3%, 31.1%, and 38.4% of MGUS patients, respectively.
Conclusions: The prevalence of MGUS is substantially lower in southern China than in whites and blacks.
{"title":"Prevalence of monoclonal gammopathy of undetermined significance in Shenzhen, China.","authors":"Anping Xu, Tong Guo, Shuping Zhang, Houlong Luo, Mengxue Shen, Yinghui Ye, Ling Ji","doi":"10.1080/16078454.2024.2352686","DOIUrl":"https://doi.org/10.1080/16078454.2024.2352686","url":null,"abstract":"<p><strong>Background: </strong>Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population.</p><p><strong>Methods: </strong>This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein.</p><p><strong>Results: </strong>A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08-1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04-2.50). The prevalence of MGUS was significantly higher in males than in females (<i>P</i> < 0.05). The median concentration of M-protein was 3.1 g/L, ranging from 0.5 g/L to 25.1 g/L. The M-protein type was IgG in 55.4% of MGUS patients, followed by IgA (31.1%), IgM (9.5%), IgD (0.5%), biclonal (2.3%), and light chain (1.2%). Abnormalities in SPE, FLC ratios, and immunoglobulin levels were observed in 78.3%, 31.1%, and 38.4% of MGUS patients, respectively.</p><p><strong>Conclusions: </strong>The prevalence of MGUS is substantially lower in southern China than in whites and blacks.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178608","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: 2024-07-12DOI: 10.1080/16078454.2024.2377849
Miao Hu, Yanfen Ma, Keli Jia, SaSa Liu, Huarong Jing, Ruicheng Li
Objectives: To explore the changes in the coagulation function of patients newly diagnosed with multiple myeloma (MM) at different stages and with different M protein types, and to analyze the correlation between coagulation indexes and β2-microglobulin (β2-MG).
Methods: A total of 371 Patients with newly diagnosed MM (n = 371) and healthy controls (n = 48) were selected from January 2016 to December 2022. Baseline data, β2-MG and coagulation index values were collected. Indexes included prothrombin time (PT), activated partial thromboplastin time (APPT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer(D-D). Patients were divided into different groups according to the Durie-Salmon staging system (DS), the International Staging System (ISS) and disease classification (M protein type). The levels of these six indexes were compared among the groups and the correlation between each index and β2-MG was analyzed.
Results: Compared to the normal control group, the levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all P < 0.001). As DS and ISS staging increased, the levels of PT, TT, FDP and D-D also increased significantly (all P < 0.001). β2-MG was positively correlated with PT, TT, and FDP levels (Spearman r = 0.157, 0.270, 0.108, respectively; all P < 0.05), and negatively correlated with FIB (r = -0.220, P < 0.001). Significant differences existed in the levels of these six indexes among different M protein types (all P < 0.001). Among them, PT and APTT increased significantly in the IgA-κ group, FIB increased in the λ light chain group, TT increased in the IgG-κ group, FDP increased in the κ light chain group, and D-D increased in the IgG-λ group.
Conclusions: The degree of coagulation dysfunction in MM patients increases with disease stage and abnormal increases of various coagulation indicators occur in different M protein types and are closely related to β2-MG.
研究目的探讨新诊断的多发性骨髓瘤(MM)患者在不同阶段、不同M蛋白类型的凝血功能变化,分析凝血指标与β2-微球蛋白(β2-MG)的相关性:方法:选取2016年1月至2022年12月期间新确诊的371例MM患者(n = 371)和健康对照组(n = 48)。收集基线数据、β2-MG 和凝血指标值。指标包括凝血酶原时间(PT)、活化部分凝血活酶时间(APPT)、纤维蛋白原(FIB)、凝血酶时间(TT)、纤维蛋白原降解产物(FDP)和D-二聚体(D-D)。根据杜里-萨尔蒙分期系统(DS)、国际分期系统(ISS)和疾病分类(M 蛋白类型)将患者分为不同的组别。比较了各组的这六项指标水平,并分析了各项指标与β2-MG之间的相关性:结果:与正常对照组相比,MM 组的 PT、FIB、TT、FDP、D-D 水平明显升高(均 P P r = 0.157、0.270、0.108;均 P r = -0.220,P P 结论:MM 组的凝血功能障碍程度明显高于正常对照组:MM患者的凝血功能障碍程度随疾病分期而加重,不同M蛋白类型的患者各种凝血指标均出现异常升高,且与β2-MG密切相关。
{"title":"Analysis of coagulation alteration and its correlation with β2-microglobulin in 371 patients with newly diagnosed multiple myeloma.","authors":"Miao Hu, Yanfen Ma, Keli Jia, SaSa Liu, Huarong Jing, Ruicheng Li","doi":"10.1080/16078454.2024.2377849","DOIUrl":"https://doi.org/10.1080/16078454.2024.2377849","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the changes in the coagulation function of patients newly diagnosed with multiple myeloma (MM) at different stages and with different M protein types, and to analyze the correlation between coagulation indexes and β2-microglobulin (β2-MG).</p><p><strong>Methods: </strong>A total of 371 Patients with newly diagnosed MM (<i>n </i>= 371) and healthy controls (<i>n </i>= 48) were selected from January 2016 to December 2022. Baseline data, β2-MG and coagulation index values were collected. Indexes included prothrombin time (PT), activated partial thromboplastin time (APPT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer(D-D). Patients were divided into different groups according to the Durie-Salmon staging system (DS), the International Staging System (ISS) and disease classification (M protein type). The levels of these six indexes were compared among the groups and the correlation between each index and β2-MG was analyzed.</p><p><strong>Results: </strong>Compared to the normal control group, the levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all <i>P </i>< 0.001). As DS and ISS staging increased, the levels of PT, TT, FDP and D-D also increased significantly (all <i>P </i>< 0.001). β2-MG was positively correlated with PT, TT, and FDP levels (Spearman <i>r </i>= 0.157, 0.270, 0.108, respectively; all <i>P </i>< 0.05), and negatively correlated with FIB (<i>r</i> = -0.220, <i>P </i>< 0.001). Significant differences existed in the levels of these six indexes among different M protein types (all <i>P </i>< 0.001). Among them, PT and APTT increased significantly in the IgA-κ group, FIB increased in the λ light chain group, TT increased in the IgG-κ group, FDP increased in the κ light chain group, and D-D increased in the IgG-λ group.</p><p><strong>Conclusions: </strong>The degree of coagulation dysfunction in MM patients increases with disease stage and abnormal increases of various coagulation indicators occur in different M protein types and are closely related to β2-MG.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590196","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: 2024-07-15DOI: 10.1080/16078454.2024.2377860
Fang Hua, Yue Hu, Guang-Cui He, Si-Han Lai, Ying He, Shan Zhang, Yan Deng, Ying Han, Xiao-Dong Liu, Kun Yang, Hui-Xiu Zhong, Jian Xiao, Zhong-Zheng Zheng, Hai Yi
Backgroud: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear.
Case presentation: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free.
Conclusion: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.
背景介绍Li-Fraumeni综合征是一种遗传性肿瘤综合征,其特点是发生恶性肿瘤,尤其是急性淋巴细胞白血病(ALL)的风险较高,可由杂合种系突变引起。TP53基因种系突变被认为是急性白血病发生和诊断的潜在危险因素和重要预后参数,但很少发生在成人中,其在急性白血病中的具体致病意义尚不清楚:我们描述了一例被诊断为 ALL 的 45 岁女性病例。全外显子组测序方法从她的骨髓样本中发现了一个可能具有致病意义的TP53种系突变,即位于第8外显子上的c.848G>A(p.Arg283His)杂合错义突变,并在她的头发、口腔粘膜和指甲样本中得到了进一步验证。家族血统筛查显示,患者的父亲和非捐献者的儿子存在相同的 TP53 基因变异,而捐献者则没有。数字聚合酶链式反应(Digital PCR)观察到,移植后该点突变频率下降,但在维持治疗期间,当患者无白血病时,该点突变频率仍然很低:结论:这例疑似李-弗劳米尼综合征病例报告中可能存在致病性杂合子 TP53 变异,从而扩大了癌症基因谱。对她的家庭成员进行基因突变筛查,有助于确定最佳亲属捐赠者,并通过监测造血干细胞移植后最小残留病的TP53种系突变,避免不必要的治疗。其在血液恶性肿瘤发展中的潜在作用和临床致病影响还需要进一步探究。
{"title":"Case report: TP53 c.848G>A germline mutation as a possible screening target at initial diagnosis for acute lymphoblastic leukemia.","authors":"Fang Hua, Yue Hu, Guang-Cui He, Si-Han Lai, Ying He, Shan Zhang, Yan Deng, Ying Han, Xiao-Dong Liu, Kun Yang, Hui-Xiu Zhong, Jian Xiao, Zhong-Zheng Zheng, Hai Yi","doi":"10.1080/16078454.2024.2377860","DOIUrl":"10.1080/16078454.2024.2377860","url":null,"abstract":"<p><strong>Backgroud: </strong>Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear.</p><p><strong>Case presentation: </strong>We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free.</p><p><strong>Conclusion: </strong>This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616196","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}