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Analysis of Updates in Multiple Myeloma Treatment and Management 多发性骨髓瘤治疗与管理的最新进展分析
Pub Date : 2023-10-04 DOI: 10.33696/haematology.4.055
Maria Jacqueline Nieto, Aryles Hedjar, Margaret Locke, Jessica Caro, Muhammad Wasif Saif
Introduction: During the past two decades, new therapeutic agents have greatly improved the treatment landscape in multiple myeloma (MM). Treatments such as proteasome inhibitors, immunomodulatory agents, targeted monoclonal antibody therapy, and chimeric antigen receptor (CAR) T-cell therapy have improved outcomes with less toxicity. Advances in laboratory testing have accompanied this change, performing faster and more accurate assessments of treatment response. Despite these advances, however, disparities in MM outcomes persist. Objective: The purpose of this study was to review epidemiological trends in MM over the past two decades and to identify disparities that may impact MM identification and survival. Methods: Retrospective analysis was conducted on adult patients diagnosed with MM between the years 2000-2019 using the November 2021 Surveillance, Epidemiology, and End Results (SEER) program database. Joinpoint models were used to calculate annual percent changes (APCs) and average annual percent change (AAPC). Results: There were a total of 111,328 diagnoses of MM extracted from the SEER database. Most patients were male (55.17%) and white (76.7%). Age-adjusted rate analysis found a significantly higher incidence among black patients compared to white patients. The APC between 2000-2015 was 1.46, and the APC between 2015-2019 was -1.34. Relative survival also increased from 2000 to 2014. The 5-year cancer survival in MM also increased at an average of 1.8% for every year after diagnosis. The annual probability of MM-related mortality at the 1-year mark also decreased from 28.5% in 2000 to 16.7% in 2018. Conclusion: Novel advances in MM therapeutic agents and diagnostic testing have paved the way for significant improvements in patient survival outcomes. Disparities persist along racial lines. Further research is needed to evaluate responses to specific MM treatment in the age of newly developed targeted therapies to overcome these disparities.
在过去的二十年中,新的治疗药物极大地改善了多发性骨髓瘤(MM)的治疗前景。诸如蛋白酶体抑制剂、免疫调节剂、靶向单克隆抗体治疗和嵌合抗原受体(CAR) t细胞治疗等治疗方法改善了结果,毒性更小。实验室检测的进步伴随着这一变化,对治疗反应进行更快和更准确的评估。然而,尽管取得了这些进展,MM结果的差异仍然存在。目的:本研究的目的是回顾过去二十年来MM的流行病学趋势,并确定可能影响MM识别和生存的差异。方法:使用2021年11月监测、流行病学和最终结果(SEER)项目数据库,对2000-2019年间诊断为MM的成年患者进行回顾性分析。采用连接点模型计算年变化百分比(APCs)和平均年变化百分比(AAPC)。结果:从SEER数据库中提取的MM诊断共111328例。以男性(55.17%)和白人(76.7%)居多。年龄调整率分析发现,黑人患者的发病率明显高于白人患者。2000-2015年APC为1.46,2015-2019年APC为-1.34。从2000年到2014年,相对存活率也有所增加。MM的5年生存率在诊断后平均每年增加1.8%。1年内mm相关死亡率的年概率也从2000年的28.5%下降到2018年的16.7%。结论:MM治疗药物和诊断测试的新进展为显著改善患者生存结果铺平了道路。种族差异依然存在。在新开发的靶向治疗时代,需要进一步的研究来评估对特异性MM治疗的反应,以克服这些差异。
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引用次数: 0
Molecular Features Associated with Response to Enasidenib Plus Azacitidine in Newly Diagnosed IDH2-Mutated Acute Myeloid Leukemia 新诊断的IDH2突变急性髓细胞白血病对依那西替尼加阿扎胞苷反应的分子特征
Pub Date : 2023-08-28 DOI: 10.33696/haematology.4.054
A. Risueño, W. See, T. Prebet, C. Dinardo, H. Döhner, E. Stein, A. Fathi, P. Vyas, L. Quek, A. Gandhi, Maroof Hasan
IDH2 gene mutations, typically at residues R140 and R172, occur in 8–19% of patients with acute myeloid leukemia (AML). These mutations induce production of 2-hydroxyglutarate (2-HG), an oncometabolite that causes DNA and histone hypermethylation, and subsequent blockade of hematopoietic cell differentiation. In a phase 1b/2 trial (NCT02677922), combination therapy with azacitidine + enasidenib significantly improved overall response rate compared with azacitidine only therapy (74% vs 36%; P<0.001) in patients with newly diagnosed IDH2-mutated AML not eligible for intensive chemotherapy. We investigated the association between molecular features and clinical outcomes from that trial. In all, 101 patients were randomized to enasidenib + azacitidine (n=68) or azacitidine only (n=33); 74% of patients had IDH2-R140. Baseline 2-HG levels and IDH2 variant allele frequency (VAF) were similar between treatment arms and IDH2 variants and were not significantly different between clinical response categories. Significant 2-HG and IDH2 VAF reductions from baseline were observed with combination therapy compared with azacitidine only. Molecular profiling revealed SRSF2 preferentially co-mutated with IDH2-R140, and DNMT3A co-mutated with IDH2-R172. IDH2 VAF was reduced to <1% in 50% of patients who achieved CR with combination therapy (18/36) and azacitidine only (2/4). VAFs of genes in the DNA methylation, receptor-tyrosine-kinase, and RAS canonical pathways were reduced in patients achieving CR. Of note, combination therapy improved event-free survival in patients with RAS-pathway mutations, which have been associated with resistance to enasidenib monotherapy.
IDH2基因突变,通常发生在R140和R172残基,发生在8-19%的急性髓细胞白血病(AML)患者中。这些突变诱导2-羟基戊二酸(2-HG)的产生,这是一种引起DNA和组蛋白超甲基化的肿瘤代谢产物,随后阻断造血细胞分化。在一项1b/2期试验(NCT02677922)中,在不符合强化化疗条件的新诊断IDH2突变AML患者中,与仅使用阿扎胞苷的治疗相比,阿扎胞苷+依那西尼的联合治疗显著提高了总有效率(74%对36%;P<0.001)。我们研究了该试验的分子特征与临床结果之间的关系。总共有101名患者被随机分配给恩那西尼+阿扎胞苷(n=68)或仅阿扎胞苷治疗(n=33);74%的患者有IDH2-R140。治疗组和IDH2变体之间的基线2-HG水平和IDH2变异等位基因频率(VAF)相似,临床反应类别之间没有显著差异。与仅阿扎胞苷相比,联合治疗观察到2-HG和IDH2 VAF较基线显著降低。分子图谱显示SRSF2优先与IDH2-R140共突变,DNMT3A与IDH2-R172共突变。在联合治疗(18/36)和仅使用阿扎胞苷(2/4)获得CR的50%患者中,IDH2 VAF降低至<1%。在达到CR的患者中,DNA甲基化、受体酪氨酸激酶和RAS经典途径中基因的VAF减少。值得注意的是,联合治疗提高了RAS途径突变患者的无事件生存率,这与埃纳西尼单药治疗的耐药性有关。
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引用次数: 0
A Rare Blood Malignancy in a Genetic Hematological Disorder: Polycythemia Vera (PV) in Sickle Cell Disease (SCD) 遗传性血液病中一种罕见的血液恶性肿瘤:镰状细胞病(SCD)中的真性红细胞增多症(PV)
Pub Date : 2023-08-12 DOI: 10.33696/haematology.4.053
C. L. Edwards, Sharena Scott, M. Boggan, J. Meek, W. J. Bryson, Alexandria McDougald, Milo Broadnax, C. Barker, Jessica Miller, J. Sollers, Tanisha I. Burford, J. Livingston, E. Whitworth, G. Byrd, Kelvin Williams, Sherry C. Eaton, Malik Muhammad, George Cliette, Dana Jones, Brianna Downey, Hilary T. Dietahin, Merrell Turner, Roland Thorpe, Keith Whitfield, Debra O. Parker, E. Robinson, M. Wood, Kenyon Railey, Shiv Sudhakar, Wandy Morel Cubilete, N. Shah
Objective: To delineate the etiology, symptomatology, and treatment of Polycythemia Vera in adults with Sickle Cell Disease. The current review contains a review of the 4 case reports that we found on the topic. To our knowledge, no other case reports exist. Methods: We reviewed the scientific literature to discover case reports that included the topic of PV. We noted consistencies in presentation, evaluation, treatment, and clinical outcomes.Results: We reviewed 4 case reports and a limited number of clinical papers on PV in SCD. We found and reported on consistencies in clinical presentation and the diversity of treatments. We reported hematological, bone marrow, and radiographic findings.Conclusions: There is great variability in the evaluation and treatment of cases of PV in SCD. We advocate for more research and deconstructing the complicated relationship between these two comorbid disorders.
目的:探讨成人镰状细胞病真性红细胞增多症的病因、症状及治疗。当前的综述包括对我们发现的关于该主题的4个病例报告的综述。据我们所知,没有其他病例报告存在。方法:我们回顾科学文献,发现包括PV主题的病例报告。我们注意到在表现、评估、治疗和临床结果方面的一致性。结果:我们回顾了4例病例报告和有限数量的关于SCD PV的临床论文。我们发现并报告了临床表现的一致性和治疗的多样性。我们报告了血液学、骨髓学和放射学的发现。结论:在SCD的PV病例的评估和治疗方面存在很大的差异。我们提倡对这两种共病之间的复杂关系进行更多的研究和解构。
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引用次数: 0
Thrombotic Events and Risk Factors for Thrombosis in Polycythemia in Senegal, West Africa 西非塞内加尔红细胞增多症的血栓事件和血栓形成的危险因素
Pub Date : 2023-06-05 DOI: 10.33696/haematology.4.052
M. Seck, E. S. Bousso, S. A. Touré, A. Sall, Maryama Ndao, S. Guèye, B. Faye, A. Diallo, Mohamed Keita, A. Touré, S. Diop
Objectives: We aim to identify thrombotic events and risk factors for thrombosis (RFT) comparing polycythemia vera (PV) and secondary polycythemia (SP) patients.Methods: We carried out a retrospective study of a cohort of 59 patients with PV (n=34) and SP (n=25) followed for a period of 14 years. Variables studied were the frequency and type of thrombosis, sociodemographic, clinical, and biological RFT. Statistical analysis was performed using SPSS software version 18. Multivariate analysis was performed to identify RFT.Results: Mean age in PV was 53 years (33 - 79) and 44.5 years (5 - 78) in SP (p=0.74). The sex ratio in PV was 1.12 and 2.57 in PS (p=0.52). Sixteen patients had thrombotic events (27.1%) including 12 PV (35.3%) versus 4 SP (16%) (p=0.09). Twenty-two thrombotic events were identified; 14 (63.7%) of arterial thrombosis and 8 (36.3%) of venous thrombosis. There were 18 thrombotic events (81.8%) in PV versus 4 (18.2%) in SP (p=0.02). Arterial thrombosis was more frequent in PV (55.6%). Thrombosis events were more frequent in female patients (59.1%). RFT in PV were age (40-59 years), hematocrit >45% and thrombocytosis ≥ 600 G/L and in SP, RFT were hematocrit >45% and hypercholesterolemia. After multivariate analysis, hematocrit >45% was the only RFT independently associated with thrombosis occurrence.Conclusion: We show through this study, a frequent occurrence of arterial thrombosis in polycythemia. Main RFT is the high hematocrit level (>45%). We insist on the interest of therapeutic bloodletting, sometimes associated with cytoreductive treatment in order to maintain a hematocrit level <45%.
目的:我们旨在通过比较真性红细胞增多症(PV)和继发性红细胞增多病(SP)患者,确定血栓形成事件和血栓形成(RFT)的危险因素。方法:我们对59名PV(n=34)和SP(n=25)患者进行了一项为期14年的回顾性研究。研究的变量包括血栓形成的频率和类型、社会人口统计学、临床和生物RFT。使用SPSS软件版本18进行统计分析。进行多变量分析以确定RFT。结果:PV患者的平均年龄为53岁(33-79),SP患者为44.5岁(5-78)(p=0.74)。PV患者的性别比为1.12,PS患者为2.57(p=0.52)。16名患者发生血栓事件(27.1%),包括12名PV患者(35.3%)和4名SP患者(16%)(p=0.09)。共发现22起血栓事件;动脉血栓形成14例(63.7%),静脉血栓形成8例(36.3%)。PV中有18个血栓事件(81.8%),而SP中有4个(18.2%)(p=0.02)。PV中动脉血栓形成更常见(55.6%)。女性患者血栓形成事件更常见(59.1%)。PV的RFT为年龄(40-59岁)、红细胞压积>45%和血小板增多≥600g/L,SP中的RFT是红细胞压容>45%和高胆固醇血症。经过多变量分析,红细胞压积>45%是唯一与血栓形成发生独立相关的RFT。结论:本研究表明,红细胞增多症是动脉血栓形成的常见病。主要RFT是高血细胞比容水平(>45%)。我们坚持对治疗性放血的兴趣,有时与细胞还原治疗相关,以保持红细胞压积水平<45%。
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引用次数: 0
Targeting ANP32A Is a Novel Strategy Against Leukemia 靶向ANP32A是治疗白血病的新策略
Pub Date : 2022-12-13 DOI: 10.33696/haematology.3.047
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引用次数: 1
Safety and Tolerability of Nilotinib in Patients with Chronic Myeloid Leukemia during Routine Clinical Practice: Results from the ERASER Study from Greece 尼洛替尼在慢性髓系白血病患者常规临床实践中的安全性和耐受性:来自希腊ERASER研究的结果
Pub Date : 2022-12-13 DOI: 10.33696/haematology.3.051
A. Symeonidis, A. Anagnostopoulos, M. Ximeri, G. Kaiafa, E. Kapsali, N. Viniou, T. Marinakis, D. Karakasis, V. Pappa, G. Vassilopoulos, D. Margaritis, Maria Tabitsika, M. Dimou
Regional real-world evidence on the safety and efficacy of tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML) is limited. This multicenter, observational, prospective study, ERASER, evaluated the safety and tolerability of nilotinib in routine clinical practice in Greece.Adult patients with newly diagnosed BCR/ABL+ chronic phase (CP) CML and those with CP CML, resistant/intolerant to prior therapy were included in this study and followed up for 36 months. Nilotinib 300 mg/400 mg twice daily was prescribed, with appropriate dose adjustment by the investigator.The analysis population (57 patients; median age, 55 years) remained in the study for a median of 34 months. Overall, 44 (77.2%) and 13 (22.8%) patients received nilotinib as first-line treatment and owing to resistance/intolerance to prior therapy, respectively. The most common adverse events (AEs) were thrombocytopenia in 8 (14%), neutropenia in 6 (10.5%), and blood bilirubin increased/hyperbilirubinemia in 10 (17.5%) patients. Permanent treatment discontinuation, including deaths and progression, occurred in 13 (22.8%) patients. Of 52 patients with available molecular response (MR), 30 achieved MR4.5 by end of the study.The study affirms the long-term safety of nilotinib in real-world setting in Greece, in patients with newly diagnosed CML, and in those with resistance/intolerance to prior therapy.
酪氨酸激酶抑制剂在慢性粒细胞白血病(CML)患者中的安全性和有效性的区域现实证据有限。这项名为ERASER的多中心、观察性、前瞻性研究评估了尼洛替尼在希腊常规临床实践中的安全性和耐受性。本研究纳入了新诊断为BCR/ABL+慢性期(CP)CML的成年患者和对既往治疗有耐药性/不耐受性的CP CML患者,并随访了36个月。尼洛替尼300mg/400mg,每日两次,由研究者进行适当的剂量调整。分析人群(57名患者;中位年龄55岁)在研究中的平均停留时间为34个月。总体而言,44名(77.2%)和13名(22.8%)患者分别因对先前治疗的耐药性/不耐受性而接受了尼洛替尼一线治疗。最常见的不良事件(AE)为8例(14%)血小板减少症,6例(10.5%)中性粒细胞减少症,10例(17.5%)患者血胆红素升高/高胆红素血症。13名(22.8%)患者出现永久性停药,包括死亡和进展。在52名有可用分子反应(MR)的患者中,有30名在研究结束时达到了MR4.5。该研究证实了尼洛替尼在希腊现实世界中的长期安全性,对新诊断的慢性粒细胞白血病患者和对先前治疗有耐药性/不耐受的患者都是如此。
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引用次数: 0
Making a Rationale Decision About -Uses of FFP: A Study at the Blood Bank of Tertiary Care Hospital of Southern Rajasthan 对FFP的使用做出合理决策:在拉贾斯坦邦南部三级护理医院血库进行的研究
Pub Date : 2022-12-13 DOI: 10.33696/haematology.3.046
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引用次数: 0
Concomitant Langerhans Cell Histiocytosis and Chronic Myelomonocytic Leukaemia Responding to 5-azacitidine 5-氮杂胞苷引起的Langerhans细胞组织细胞增多症和慢性粒细胞白血病
Pub Date : 2022-12-13 DOI: 10.33696/haematology.3.050
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引用次数: 0
B-cell Acute Lymphoblastic Leukemia with a Normal Platelet Count, Presenting as a Limp in a 2-year-old Child 2岁儿童b细胞急性淋巴细胞白血病伴正常血小板计数,表现为跛行
Pub Date : 2022-12-13 DOI: 10.33696/haematology.3.048
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引用次数: 0
Multiple Myeloma with Neutrophilia: Two Etiologic Pathways for a Rare Presentation of a Common Diagnosis 多发性骨髓瘤伴中性粒细胞增多症:罕见常见诊断的两种病因途径
Pub Date : 2022-12-13 DOI: 10.33696/haematology.3.049
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引用次数: 0
期刊
Journal of clinical haematology
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