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Transdifferentiation From Multiple Myeloma to Myeloid Sarcoma in the Setting of CAR T-Cell Therapy CAR - t细胞治疗下多发性骨髓瘤向髓系肉瘤的转分化。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.09.013
Diana Cirstea , Kathleen Gallagher , Maxx King , Paola Dal Cin , Mark J Sloan , Marcela V Maus , Noopur Raje , Matthew Frigault , Valentina Nardi
  • The introduction of anti-BCMA CAR T-cell therapies has improved the prognosis for patients with multiple myeloma. However, long-term remission remains elusive for many patients due to various resistance mechanisms. Here we discuss a unique case of a 56-year-old woman whose multiple myeloma transdifferentiated into myeloid sarcoma shortly after receiving BCMA-targeted CAR T-cell therapy (ciltacabtagene autoleucel).
  • Our report presents the first documented case of multiple myeloma transdifferentiating into myeloid sarcoma following BCMA-targeted CAR T-cell therapy, specifically with ciltacabtagene autoleucel, making a novel observation in the field of oncology.
  • Myeloid sarcoma cells retaining the same genetic abnormalities as the original myeloma cells, including the IgH/FGFR3 translocation, suggest a clonal relationship, highlighting potential lineage plasticity in myeloma and its role in therapy resistance.
  • Clinicians should be vigilant for signs of lineage switch in patients undergoing CAR T-cell therapy, particularly in those with high-risk genetic features.
  • In cases of suspected transdifferentiation, a multidisciplinary approach involving hematology, oncology, and pathology is essential for diagnosis and management.
  • This case underscores the need for further research into the mechanisms of lineage plasticity in multiple myeloma and the potential role of CAR T-cell therapy in driving such changes.
•抗bcma CAR - t细胞疗法的引入改善了多发性骨髓瘤患者的预后。然而,由于各种耐药机制,许多患者的长期缓解仍然难以捉摸。在这里,我们讨论一个56岁的女性,她的多发性骨髓瘤在接受bcma靶向CAR -t细胞治疗后不久就转分化为髓系肉瘤。•我们的报告提出了第一个记录的多发性骨髓瘤在bcma靶向CAR -t细胞治疗后转分化为髓系肉瘤的病例,特别是西他卡他烯自体甲醇,在肿瘤学领域进行了新的观察。•髓系肉瘤细胞保留与原始骨髓瘤细胞相同的遗传异常,包括IgH/FGFR3易位,表明存在克隆关系,突出了骨髓瘤中潜在的谱系可塑性及其在治疗耐药性中的作用。•临床医生应警惕接受CAR - t细胞治疗的患者谱系转换的迹象,特别是那些具有高风险遗传特征的患者。•在疑似转分化的病例中,包括血液学、肿瘤学和病理学在内的多学科方法对诊断和治疗至关重要。•该病例强调需要进一步研究多发性骨髓瘤谱系可塑性的机制以及CAR - t细胞治疗在推动这种变化中的潜在作用。
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引用次数: 0
Real-World Comparison of Treatment Outcomes for Multiple Myeloma in Elderly Transplant Ineligible Patients Receiving First-Line VRd, Rd and VCd: Results From the Australian and New Zealand Myeloma and Related Diseases Registry 接受一线VRd、Rd和VCd的老年移植不合格患者多发性骨髓瘤治疗结果的现实世界比较:来自澳大利亚和新西兰骨髓瘤及相关疾病登记处的结果
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.08.004
Sarah Zhao , Cameron Wellard , Elizabeth M Moore , Andrew Spencer , Hang Quach , P. Joy Ho , Emma-Jane McDonald , Peter Mollee , Simon J Harrison , Bradley Augustson , Erica M Wood , Zoe K McQuilten , Rajeev Rajagopal

Background

Real-world data on treatment outcomes for elderly transplant-ineligible patients with newly diagnosed multiple myeloma are limited. The difference in treatment subsidization in Australia compared with New Zealand enables comparison of bortezomib-cyclophosphamide-dexamethasone (VCd), lenalidomide-bortezomib-dexamethasone (VRd) with Rd maintenance, and continuous Rd.

Methods

Using data from the ANZ Myeloma and Related Diseases Registry, we evaluated 1092 patients over 70 years of age between February 2013 and February 2024. Those who received Rd, VRd or VCd induction, and did not undergo an autologous stem cell transplant were included.

Results

Overall response rates were 85.6%, 73.7%, and 91.5% for VCd, Rd, and VRd, respectively (P < 0.001). At a median follow-up of 37 months, VRd showed the longest median progression-free survival (PFS) of 27.5 months, compared to 23.7 months for Rd and 20.5 months for VCd (P = 0.01). After adjustment, PFS for VRd and Rd remained superior compared to VCd. Rd patients had the longest median time to next treatment (35.1 months), compared to 28.7 months for VRd and 20.1 months for VCd. Overall survival (OS) was superior with VRd (P = 0.039), with 3-year survival rates of 80% for VRd, 67% for Rd, and 67% for VCd. However, multivariate analysis did not show a significant difference in OS.

Conclusion

Our study confirms VRd demonstrates superior PFS compared to Rd and VCd, but was underpowered to detect a significant difference in OS. More prospective real-world studies are needed to establish the optimal choice of induction therapy balancing efficacy and toxicity for this cohort in resource limited settings.
背景:新诊断的老年不适合移植的多发性骨髓瘤患者的治疗结果的真实数据是有限的。与新西兰相比,澳大利亚在治疗补贴方面的差异使得硼替佐米-环磷酰胺-地塞米松(VCd)、来那度胺-硼替佐米-地塞米松(VRd)与Rd维持和持续Rd进行比较。方法:使用来自ANZ骨髓瘤和相关疾病登记处的数据,我们评估了2013年2月至2024年2月期间1092名70岁以上的患者。接受Rd、VRd或VCd诱导且未接受自体干细胞移植的患者也包括在内。结果:VCd、Rd和VRd的总有效率分别为85.6%、73.7%和91.5% (P < 0.001)。在中位随访37个月时,VRd显示最长的中位无进展生存期(PFS)为27.5个月,而Rd为23.7个月,VCd为20.5个月(P = 0.01)。调整后,VRd和Rd的PFS仍优于VCd。Rd患者到下一次治疗的中位时间最长(35.1个月),而VRd患者为28.7个月,VCd患者为20.1个月。VRd组的总生存率(OS)优于VRd组(P = 0.039), VRd组的3年生存率为80%,Rd组为67%,VCd组为67%。然而,多变量分析未显示OS有显著差异。结论:我们的研究证实VRd与Rd和VCd相比具有更好的PFS,但不足以检测OS的显着差异。在资源有限的情况下,需要更多的前瞻性现实世界研究来确定诱导治疗平衡疗效和毒性的最佳选择。
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引用次数: 0
Intravascular Complications of Central Venous Catheterization in Chronic Hematological Diseases: Low Risk with Peripherally Inserted Catheters in a Single-Center Retrospective Large Study 慢性血液病中心静脉置管的血管内并发症:在一项单中心回顾性大型研究中,外周置管的低风险
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.09.011
Claudia Giordano, Marco Picardi, Annamaria Vincenzi, Alessia Scarpa, Fabrizio Pane

Introduction

To evaluate the impact of long-term peripherally inserted central catheters (PICC) on symptomatic venous thrombosis (s-VT), we reviewed clinical charts of patients suffering from chronic hematological diseases with in-situ PICC placement for at least 90 days after catheterization at the Hematology Unit of the Federico II University Medical School of Naples (Italy). The period of observation was between January 2014 and December 2023.

Methods

A total of 1150 PICCs were inserted into 1150 patients at the hematologic diagnosis. Underlying chronic diseases were the following: non-Hodgkin lymphoma (n = 760, 66.1%), Hodgkin lymphoma (n = 200, 17.4%), multiple myeloma (n = 100, 8.7%), chronic lymphocytic leukemia (n = 50, 4.3%), severe aplastic anemia (n = 15, 1.3%), sickle cell disease (n = 10, 0.9%), thalassemia (n = 10, 0.9%), and hemophilia (n = 5, 0.4%). PICCs were successfully inserted in all cases. The median duration of in-situ PICC placement was 300 days (range, 120-400 days).

Results

A s-VT occurred in 30 cases (2.6%), with a rate of 0.13 (95% CI, 0.04-0.30) per 1000 implantation days. The median period time between PICC insertion and thrombotic episode was 30 days (range, 4-95 days). No serious complication was associated with these events. Hodgkin lymphoma (compared to the other diseases) resulted in a numerically higher incidence of PICC-related s-VT.

Conclusion

PICCs represent a useful and safe frontline central vascular approach for patients with chronic hematologic diseases, with a thrombotic risk profile comparable to that reported with centrally inserted totally implantable venous access devices (TIVADs).
简介:为了评估长期外周插入中心导管(PICC)对症状性静脉血栓形成(s-VT)的影响,我们回顾了那不勒斯(意大利)费德里克二世大学医学院血液科原位放置PICC的慢性血液病患者在置管后至少90天的临床图表。观察期为2014年1月至2023年12月。方法:对1150例血液学诊断患者共置入1150个picc。潜在的慢性疾病如下:非霍奇金淋巴瘤(n = 760, 66.1%)、霍奇金淋巴瘤(n = 200, 17.4%)、多发性骨髓瘤(n = 100, 8.7%)、慢性淋巴细胞白血病(n = 50, 4.3%)、严重再生障碍性贫血(n = 15, 1.3%)、镰状细胞病(n = 10, 0.9%)、地中海贫血(n = 10, 0.9%)和血友病(n = 5, 0.4%)。所有病例均成功插入picc。PICC原位放置的中位持续时间为300天(范围为120-400天)。结果:30例(2.6%)发生s-VT,发生率为0.13 (95% CI, 0.04 ~ 0.30) / 1000天。PICC置入至血栓发作的中位时间为30天(范围4-95天)。这些事件均无严重并发症。霍奇金淋巴瘤(与其他疾病相比)导致picc相关s-VT的发生率更高。结论:PICCs为慢性血液病患者提供了一种有效且安全的一线中心血管途径,其血栓形成风险与中心插入式全植入式静脉通路装置(TIVADs)相当。
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引用次数: 0
SOHO State of the Art Updates and Next Questions | Current and Emerging Novel Treatments for Marginal Zone Lymphoma SOHO最新进展和下一个问题|边缘区淋巴瘤当前和新兴的新治疗方法。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.05.021
Izidore S. Lossos
Marginal zone lymphoma (MZL) is a heterogeneous disease representing 7% to 10% of non-Hodgkin lymphomas (NHL). There are no clear guidelines defining the need for treatment initiation and no standardized therapeutic approach for patients with MZL. Previously, many treatments were extrapolated from clinical trials that mainly enrolled patients with follicular lymphoma and did not have statistical power to show treatment efficacy specifically in MZL patients. Currently, the field is moving toward conducting specific trials in MZL patients with specific inclusion criteria for each MZL subtype, assessing response distinctively in FDG avid and nonavid MZL tumors and using MZL-relevant primary endpoints. Herein I briefly describe these changes, summarize previous therapeutic studies in MZL and present preliminary publicly available data on novel emerging treatments, including bispecific antibodies, antibody drug conjugates and novel targeted therapies.
边缘带淋巴瘤(MZL)是一种异质性疾病,占非霍奇金淋巴瘤(NHL)的7%至10%。目前还没有明确的指南来定义MZL患者开始治疗的必要性,也没有标准化的治疗方法。以前,许多治疗方法都是从临床试验中推断出来的,这些临床试验主要招募滤泡性淋巴瘤患者,并且没有统计学上的力量来显示治疗效果,特别是在MZL患者中。目前,该领域正朝着在MZL患者中开展特定试验的方向发展,针对每种MZL亚型制定特定的纳入标准,评估FDG依赖型和非依赖型MZL肿瘤的独特反应,并使用MZL相关的主要终点。在此,我简要地描述了这些变化,总结了MZL先前的治疗研究,并介绍了新的新兴治疗方法的初步公开数据,包括双特异性抗体,抗体药物偶联物和新的靶向治疗。
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引用次数: 0
Curability Potential of Low-Grade Follicular Lymphoma 低级别滤泡性淋巴瘤的治愈潜力。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.09.009
F. Cabanillas , J.G. Conde , T. Gutierrez , A. Torres , J. Abreu , F.B. Hagemeister

Background

Classic follicular lymphoma is generally considered incurable. Standard management includes a “watch and wait” strategy for patients with low tumor burden, while those with high tumor burden typically receive chemotherapy.

Objectives

We aimed to evaluate the potential for curability in a cohort of patients managed with systemic therapy, without the use of a watch-and-wait approach.

Methods

This study is a retrospective, real-world analysis of patients treated in routine clinical practice. We analyzed 183 previously untreated patients with low-grade follicular lymphoma (LGFL) treated at Auxilio Mutuo Cancer Center in Puerto Rico between June 2002 and July 2023. All patients began therapy shortly after diagnosis, without observation. We stratified treatment based on the presence or absence of “clinically discordant indolent histology” (CDIH), defined by aggressive clinical features such as B symptoms, high lactic dehydrogenase (LDH), SUV >14 on PET, Ki-67 > 30%, or involvement of atypical sites including lung, pleura, soft-tissue, CNS and bones. Patients with CDIH typically received R-CHOP x6 followed by FND (fludarabine, Novantrone [mitoxantrone] and dexamethasone). Non-CDIH patients mostly received FND-R. All patients received 2 years of rituximab maintenance. The primary endpoint was failure-free survival (FFS).

Results

Among 183 patients, the median follow-up for censored cases was 8.5 years (range: 6 to 261 months). At 10 years, the FFS was 80%; at 15 years, 75%. Of 61 patients followed for more than 10 years, 57 (93%) remain relapse-free, suggesting a potential for cure in those who remain failure-free beyond a decade.

Conclusion

Our findings support the hypothesis that early initiation of chemotherapy may potentially result in cure for patients with classic follicular NHL. These results warrant confirmation in future prospective studies.
背景:典型滤泡性淋巴瘤通常被认为是无法治愈的。标准管理包括对肿瘤负担低的患者采取“观察和等待”策略,而肿瘤负担高的患者通常接受化疗。目的:我们旨在评估在不使用观察和等待方法的情况下,接受全身治疗的患者队列的治愈潜力。方法:本研究对在常规临床实践中接受治疗的患者进行回顾性分析。我们分析了2002年6月至2023年7月期间在波多黎各Auxilio Mutuo癌症中心治疗的183例未经治疗的低级别滤泡性淋巴瘤(LGFL)患者。所有患者在诊断后不久开始治疗,未进行观察。我们根据是否存在“临床不一致的惰性组织学”(CDIH)对治疗进行分层,CDIH的定义是侵略性的临床特征,如B症状、高乳酸脱氢酶(LDH)、PET上的SUV >4、Ki-67 > 30%,或累及非典型部位,包括肺、胸膜、软组织、中枢神经系统和骨骼。CDIH患者通常接受R-CHOP x6,随后接受FND(氟达拉滨、诺vantrone[米托蒽醌]和地塞米松)。非cdih患者大多接受FND-R治疗。所有患者均接受2年美罗华维持治疗。主要终点为无故障生存期(FFS)。结果:在183例患者中,审查病例的中位随访时间为8.5年(范围:6至261个月)。十年后,FFS占80%;15年,75%。在61例随访超过10年的患者中,57例(93%)仍然没有复发,这表明那些在10年以上没有复发的患者有治愈的潜力。结论:我们的研究结果支持了早期化疗可能导致经典滤泡性NHL患者治愈的假设。这些结果值得在未来的前瞻性研究中得到证实。
{"title":"Curability Potential of Low-Grade Follicular Lymphoma","authors":"F. Cabanillas ,&nbsp;J.G. Conde ,&nbsp;T. Gutierrez ,&nbsp;A. Torres ,&nbsp;J. Abreu ,&nbsp;F.B. Hagemeister","doi":"10.1016/j.clml.2025.09.009","DOIUrl":"10.1016/j.clml.2025.09.009","url":null,"abstract":"<div><h3>Background</h3><div>Classic follicular lymphoma is generally considered incurable. Standard management includes a “watch and wait” strategy for patients with low tumor burden, while those with high tumor burden typically receive chemotherapy.</div></div><div><h3>Objectives</h3><div>We aimed to evaluate the potential for curability in a cohort of patients managed with systemic therapy, without the use of a watch-and-wait approach.</div></div><div><h3>Methods</h3><div>This study is a retrospective, real-world analysis of patients treated in routine clinical practice. We analyzed 183 previously untreated patients with low-grade follicular lymphoma (LGFL) treated at Auxilio Mutuo Cancer Center in Puerto Rico between June 2002 and July 2023. All patients began therapy shortly after diagnosis, without observation. We stratified treatment based on the presence or absence of “clinically discordant indolent histology” (CDIH), defined by aggressive clinical features such as B symptoms, high lactic dehydrogenase (LDH), SUV &gt;14 on PET, Ki-67 &gt; 30%, or involvement of atypical sites including lung, pleura, soft-tissue, CNS and bones. Patients with CDIH typically received R-CHOP x6 followed by FND (fludarabine, Novantrone [mitoxantrone] and dexamethasone). Non-CDIH patients mostly received FND-R. All patients received 2 years of rituximab maintenance. The primary endpoint was failure-free survival (FFS).</div></div><div><h3>Results</h3><div>Among 183 patients, the median follow-up for censored cases was 8.5 years (range: 6 to 261 months). At 10 years, the FFS was 80%; at 15 years, 75%. Of 61 patients followed for more than 10 years, 57 (93%) remain relapse-free, suggesting a potential for cure in those who remain failure-free beyond a decade.</div></div><div><h3>Conclusion</h3><div>Our findings support the hypothesis that early initiation of chemotherapy may potentially result in cure for patients with classic follicular NHL. These results warrant confirmation in future prospective studies.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 1","pages":"Pages e103-e109"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279111","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}
引用次数: 0
SOHO State of the Art Updates and Next Questions | The Optimal Management of Waldenström Macroglobulinemia SOHO国家的艺术更新和下一个问题| Waldenström巨球蛋白血症的最佳管理。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.06.017
Alberto Guijosa , Alicia de las Heras , Shayna Sarosiek , Jorge J. Castillo
Waldenström macroglobulinemia (WM) is a rare IgM-secreting lymphoplasmacytic lymphoma with recurrent somatic mutations in MYD88 and CXCR4 observed in the malignant cells of >90% and 30% to 40% of the patients. Given its rarity, WM poses specific diagnostic and management challenges. The diagnosis of WM is clinicopathological and no pathognomonic findings exist. The combination of a monoclonal IgM paraproteinemia, lymphoplasmacytic lymphoma in the bone marrow or other organs, and the MYD88 L265P mutation makes a diagnosis of WM with a high specificity. Approximately, a third of the patients will be asymptomatic at diagnosis and the best approach is to observe, as these patients have similar survival rates than age, sex and year of diagnosis-matched individuals of the general population. Eighty percent of patients diagnosed with asymptomatic WM will need treatment within 10 years. Treatment is indicated in symptomatic patients in whom the symptoms affect the patients’ activities and are likely to be caused by the disease process. Multiple standard treatment options are safe and effective in symptomatic patients, including rituximab in combination with alkylating agents or proteasome inhibitors, covalent BTK inhibitors, and BCL2 antagonists. Noncovalent BTK inhibitors have emerged as a novel treatment option. Second-generation BCL2 antagonists, BTK degraders, antibody-drug conjugates and bispecific T-cell engagers are being evaluated in clinical trials. Multinational collaborative consortia to accelerate clinical trial design and execution in WM have emerged in Europe and the United States.
Waldenström巨球蛋白血症(macroglobulinemia, WM)是一种罕见的igm分泌性淋巴浆细胞性淋巴瘤,MYD88和CXCR4的体细胞突变在bbb90 %和30% ~ 40%的患者的恶性细胞中反复出现。鉴于其罕见性,WM提出了具体的诊断和管理挑战。WM的诊断是临床病理的,没有病理表现。结合单克隆IgM副蛋白血症、骨髓或其他器官淋巴浆细胞性淋巴瘤和MYD88 L265P突变,诊断WM具有高特异性。大约三分之一的患者在诊断时无症状,最好的方法是观察,因为这些患者的生存率与一般人群中年龄、性别和年份的诊断相匹配的个体相似。80%被诊断为无症状WM的患者将在10年内需要治疗。治疗适用于有症状的患者,这些患者的症状影响患者的活动,并且很可能是由疾病过程引起的。对于有症状的患者,多种标准治疗方案是安全有效的,包括利妥昔单抗联合烷基化剂或蛋白酶体抑制剂、共价BTK抑制剂和BCL2拮抗剂。非共价BTK抑制剂已成为一种新的治疗选择。第二代BCL2拮抗剂、BTK降解剂、抗体-药物偶联物和双特异性t细胞接合物正在临床试验中进行评估。加速WM临床试验设计和执行的跨国合作联盟已经在欧洲和美国出现。
{"title":"SOHO State of the Art Updates and Next Questions | The Optimal Management of Waldenström Macroglobulinemia","authors":"Alberto Guijosa ,&nbsp;Alicia de las Heras ,&nbsp;Shayna Sarosiek ,&nbsp;Jorge J. Castillo","doi":"10.1016/j.clml.2025.06.017","DOIUrl":"10.1016/j.clml.2025.06.017","url":null,"abstract":"<div><div>Waldenström macroglobulinemia (WM) is a rare IgM-secreting lymphoplasmacytic lymphoma with recurrent somatic mutations in <em>MYD88</em> and <em>CXCR4</em> observed in the malignant cells of &gt;90% and 30% to 40% of the patients. Given its rarity, WM poses specific diagnostic and management challenges. The diagnosis of WM is clinicopathological and no pathognomonic findings exist. The combination of a monoclonal IgM paraproteinemia, lymphoplasmacytic lymphoma in the bone marrow or other organs, and the MYD88 L265P mutation makes a diagnosis of WM with a high specificity. Approximately, a third of the patients will be asymptomatic at diagnosis and the best approach is to observe, as these patients have similar survival rates than age, sex and year of diagnosis-matched individuals of the general population. Eighty percent of patients diagnosed with asymptomatic WM will need treatment within 10 years. Treatment is indicated in symptomatic patients in whom the symptoms affect the patients’ activities and are likely to be caused by the disease process. Multiple standard treatment options are safe and effective in symptomatic patients, including rituximab in combination with alkylating agents or proteasome inhibitors, covalent BTK inhibitors, and BCL2 antagonists. Noncovalent BTK inhibitors have emerged as a novel treatment option. Second-generation BCL2 antagonists, BTK degraders, antibody-drug conjugates and bispecific T-cell engagers are being evaluated in clinical trials. Multinational collaborative consortia to accelerate clinical trial design and execution in WM have emerged in Europe and the United States.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 1","pages":"Pages 8-17"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667321","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}
引用次数: 0
When ICAN(S) Becomes ICAN’T: Clinician and Staff Perspectives on In-Hospital Neurotoxicity Grading 当ICAN(S)变成ICAN’t:临床医生和工作人员对院内神经毒性分级的看法。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.08.021
Grace M. Ferri , Allison Frank , Daniel Li , Pria Anand , Maya Abdallah , Vanessa Avalone , J. Mark Sloan , Vaishali Sanchorawala , Adam Lerner , Raphael E. Szalat , Fabio Petrocca , Camille V. Edwards , Britney N. Bell

Purpose

Guidelines from the American Society for Transplantation and Cellular Therapy (ASTCT) propose use of the Immune Effector Cell-Associated Encephalopathy (ICE) score as a means by which to grade Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). However, ICE scoring may not appropriately capture ICANS among patients with limited English proficiency or diverse educational or cultural backgrounds. With the development of protocols for early ICANS treatment and the advent of CAR-T repurposing for solid tumors, creation of an accessible neurotoxicity grading framework (and an accurate clinical correlate) for all patients is paramount.

Methods

Using a quantitative and qualitative descriptive study design, we surveyed staff members at a United States safety-net hospital experienced in grading the ICE score. We then performed an iterative thematic analysis of data embedded within free-text responses and used a modified version of the theoretical framework of acceptability (TFA) to guide evaluation of the anticipated intervention.

Results

Of the 36 survey respondents, most (27/36, 75%) agreed that lack of language concordance could lead to inaccurate ICE scores. While translation services were thought to be used appropriately (33/36, 92%), logistical barriers including availability of interpreter services (in-person, phone, tablet) were thought to impact quality of care for non-native English-speaking patients. Additional barriers to accurate ICE scoring included patient literacy, numeracy (eg, cultural differences in measuring time), education level, or disability status (eg, hearing or vision loss, memory or cognitive impairment).

Conclusion

This needs assessment demonstrated stakeholder perspectives on the standard ICE score; associated challenges among patients with limited English proficiency and illiteracy; and the utility of an alternative language-concordant and culturally humble grading system for neurotoxicity among non-native English speakers.
目的:美国移植和细胞治疗学会(ASTCT)的指南建议使用免疫效应细胞相关脑病(ICE)评分作为对免疫效应细胞相关神经毒性综合征(ICANS)进行分级的一种手段。然而,ICE评分可能不能恰当地反映英语水平有限或教育或文化背景不同的患者的ICANS。随着早期ICANS治疗方案的发展和CAR-T重新用于实体瘤的出现,为所有患者创建一个可访问的神经毒性分级框架(以及准确的临床相关性)是至关重要的。方法:采用定量和定性描述性研究设计,我们调查了美国一家安全网医院的工作人员,他们对ICE评分有经验。然后,我们对自由文本回复中嵌入的数据进行了迭代主题分析,并使用可接受性理论框架(TFA)的修改版本来指导预期干预的评估。结果:在36个调查对象中,大多数(27/ 36,75%)认为缺乏语言一致性可能导致ICE评分不准确。虽然翻译服务被认为得到了适当的使用(33/ 36,92%),但后勤障碍,包括口译服务(面对面、电话、平板电脑)的可用性,被认为会影响非英语母语患者的护理质量。影响准确ICE评分的其他障碍包括患者读写能力、计算能力(如测量时间的文化差异)、教育水平或残疾状况(如听力或视力丧失、记忆或认知障碍)。结论:该需求评估展示了利益相关者对标准ICE评分的看法;英语水平有限和文盲患者的相关挑战;以及在非英语母语者中使用另一种语言一致和文化谦逊的神经毒性评分系统的效用。
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引用次数: 0
Impact of Measurable Residual Disease Status on Outcomes After HLA-Matched Donor Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia 可测量的残留疾病状态对hla匹配供体异体造血细胞移植后急性髓系白血病预后的影响。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.08.011
Moazzam Shahzad , Muhammad Kashif Amin , Sohaib Irfan , Abhinav Vyas , Rania Ahsan , Sibgha Gull Chaudhary , Iqra Anwar , Matthew McGuirk , Raheel Iftikhar , Haitham Abdelhakim , Anurag K. Singh , Mehdi Hamadani , Joseph P. Mcguirk , Muhammad Umair Mushtaq

Background

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a key treatment for acute myeloid leukemia (AML). Measurable residual disease (MRD) predicts post-transplant outcomes. This study evaluates the impact of pretransplant MRD status on outcomes in AML patients undergoing allo-HCT.

Methods

We retrospectively analyzed AML patients who underwent allo-HCT from matched related or unrelated donors (2013–2018) using the CIBMTR P-5646 dataset. Patients were stratified by pretransplant MRD status. Outcomes included overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), acute graft-versus-host disease (aGVHD), GVHD-free relapse-free survival (GRFS), and engraftment. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using multivariate Cox regression, adjusted for significant univariate variables (P < .05).

Results

Of 2404 AML patients (354 MRD-positive, 2050 MRD-negative), MRD-positive patients had a lower Karnofsky performance status (≥90%: 46.1% vs. 55.1%, P = .004) and were more likely to undergo myeloablative conditioning (66.6% vs. 52.7%, P < .001). MRD positivity predicted worse OS (HR 1.91, 95% CI 1.62-2.23, P < .001), DFS (HR 2.05, 95% CI 1.77–2.36, P < .001), relapse (HR 2.25, 95% CI 1.91-2.64, P < .001), aGVHD grade II to IV (HR 1.24, 95% CI 1.03-1.50, P = .024), GRFS (HR 1.59, 95% CI 1.41-1.81, P < .001), and slower platelet engraftment (HR 0.71, 95% CI 0.63-0.81, P < .001). NRM (P = .387) and neutrophil engraftment (P = .159) were similar.

Conclusion

Pretransplant MRD status predicts post-allo-HCT outcomes, with MRD positivity associated with reduced overall and disease-free survival and increased relapse risk. Personalized MRD-directed strategies are needed to optimize outcomes in AML patients undergoing allogeneic transplantation.
背景:同种异体造血干细胞移植是急性髓系白血病(AML)的关键治疗手段。可测量的残留疾病(MRD)预测移植后的预后。本研究评估移植前MRD状态对接受同种异体hct治疗的AML患者预后的影响。方法:我们使用CIBMTR P-5646数据集回顾性分析了2013-2018年从匹配的相关或非相关供体接受同种异体hct治疗的AML患者。根据移植前MRD状态对患者进行分层。结果包括总生存期(OS)、无病生存期(DFS)、复发、非复发死亡率(NRM)、急性移植物抗宿主病(aGVHD)、无移植物抗宿主病无复发生存期(GRFS)和移植物。采用多变量Cox回归计算风险比(HR)和95%置信区间(CI),并对显著单变量进行校正(P < 0.05)。结果:2404例AML患者(354例mrd阳性,2050例mrd阴性)中,mrd阳性患者的Karnofsky表现状态较低(≥90%:46.1%对55.1%,P = 0.004),更有可能接受清髓调节(66.6%对52.7%,P < 0.001)。MRD阳性预测较差的OS (HR 1.91, 95% CI 1.62-2.23, P < 0.001)、DFS (HR 2.05, 95% CI 1.77-2.36, P < 0.001)、复发(HR 2.25, 95% CI 1.91-2.64, P < 0.001)、aGVHD II至IV级(HR 1.24, 95% CI 1.03-1.50, P = 0.024)、GRFS (HR 1.59, 95% CI 1.41-1.81, P < 0.001)和血小板植入较慢(HR 0.71, 95% CI 0.63-0.81, P < 0.001)。NRM (P = .387)和中性粒细胞移植(P = .159)相似。结论:移植前MRD状态预测同种异体移植后的预后,MRD阳性与总生存率和无病生存率降低以及复发风险增加相关。需要个性化的mrd导向策略来优化接受同种异体移植的AML患者的预后。
{"title":"Impact of Measurable Residual Disease Status on Outcomes After HLA-Matched Donor Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia","authors":"Moazzam Shahzad ,&nbsp;Muhammad Kashif Amin ,&nbsp;Sohaib Irfan ,&nbsp;Abhinav Vyas ,&nbsp;Rania Ahsan ,&nbsp;Sibgha Gull Chaudhary ,&nbsp;Iqra Anwar ,&nbsp;Matthew McGuirk ,&nbsp;Raheel Iftikhar ,&nbsp;Haitham Abdelhakim ,&nbsp;Anurag K. Singh ,&nbsp;Mehdi Hamadani ,&nbsp;Joseph P. Mcguirk ,&nbsp;Muhammad Umair Mushtaq","doi":"10.1016/j.clml.2025.08.011","DOIUrl":"10.1016/j.clml.2025.08.011","url":null,"abstract":"<div><h3>Background</h3><div>Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a key treatment for acute myeloid leukemia (AML). Measurable residual disease (MRD) predicts post-transplant outcomes. This study evaluates the impact of pretransplant MRD status on outcomes in AML patients undergoing allo-HCT.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed AML patients who underwent allo-HCT from matched related or unrelated donors (2013–2018) using the CIBMTR P-5646 dataset. Patients were stratified by pretransplant MRD status. Outcomes included overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), acute graft-versus-host disease (aGVHD), GVHD-free relapse-free survival (GRFS), and engraftment. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using multivariate Cox regression, adjusted for significant univariate variables (<em>P</em> &lt; .05).</div></div><div><h3>Results</h3><div>Of 2404 AML patients (354 MRD-positive, 2050 MRD-negative), MRD-positive patients had a lower Karnofsky performance status (≥90%: 46.1% vs. 55.1%, <em>P</em> = .004) and were more likely to undergo myeloablative conditioning (66.6% vs. 52.7%, <em>P</em> &lt; .001). MRD positivity predicted worse OS (HR 1.91, 95% CI 1.62-2.23, <em>P</em> &lt; .001), DFS (HR 2.05, 95% CI 1.77–2.36, <em>P</em> &lt; .001), relapse (HR 2.25, 95% CI 1.91-2.64, <em>P</em> &lt; .001), aGVHD grade II to IV (HR 1.24, 95% CI 1.03-1.50, <em>P</em> = .024), GRFS (HR 1.59, 95% CI 1.41-1.81, <em>P</em> &lt; .001), and slower platelet engraftment (HR 0.71, 95% CI 0.63-0.81, <em>P</em> &lt; .001). NRM (<em>P</em> = .387) and neutrophil engraftment (<em>P</em> = .159) were similar.</div></div><div><h3>Conclusion</h3><div>Pretransplant MRD status predicts post-allo-HCT outcomes, with MRD positivity associated with reduced overall and disease-free survival and increased relapse risk. Personalized MRD-directed strategies are needed to optimize outcomes in AML patients undergoing allogeneic transplantation.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 1","pages":"Pages e23-e31"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032634","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}
引用次数: 0
Molecular Milestones and Survival Outcomes of Ponatinib Treatment in Patients With Chronic Myeloid Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: A Real-World Analysis 波纳替尼治疗慢性髓性白血病和费城染色体阳性急性淋巴细胞白血病患者的分子里程碑和生存结果:现实世界分析。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.09.003
Tai-Chung Tseng MD , Yu-Sung Chang MD , Xavier Cheng-Hong Tsai PhD , Ming-En Lin PhD , Feng-Ming Tien MMS , Huai-Hsuan Huang MD , Yun-Chu Lin MD , Jia-Hau Liu MD , Ming-Chih Liu BS , Chien-Chin Lin PhD , Chieh-Lung Cheng PhD , Szu-Chun Hsu MD , Ming Yao MD , Mei-Hsuan Tseng MS , Yen-Ling Peng MS , Bor-Sheng Ko PhD , Yung-Li Yang PhD , Shiann-Tarng Jou PhD , Hsin-An Hou PhD , Wen-Chien Chou PhD

Background

Ponatinib, a third-generation tyrosine kinase inhibitor, has demonstrated its activity against chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, real-world data, particularly in Asian populations, remain limited.

Methods

Patients with CML or Ph+ ALL treated with ponatinib in Taiwan between March 2013 and November 2024 were retrospectively collected. Molecular and cytogenetic data, efficacy outcomes (complete hematologic response [CHR], molecular response [MR], progression-free survival [PFS], overall survival [OS]), and adverse events were analyzed.

Results

Among 52 patients (27 CML and 25 Ph+ ALL; median follow-up: 50.7 months), 94% received ponatinib due to relapsed or refractory disease. Among patients without prior CHR, 89% reached CHR at 12 months. Among patients without prior MR, 57% had MR2.0, 53% MR3.0, and 26% MR5.0 at 12 months. MR2.0 at 6 months and MR3.0 at 12 months correlated with improved outcome in patients with CML. Additional chromosomal abnormalities (ACAs) were identified in 36% of patients and were associated with inferior survival, whereas kinase domain mutations in 78% of studied patients, including T315I (57%), did not affect the outcome. MR3.0 at any time predicted superior OS and PFS in patients with CML, and MR5.0 with superior PFS in patients with Ph+ ALL. One patient (1.9%) had an arterial occlusive event.

Conclusion

Ponatinib demonstrated substantial real-world efficacy in pretreated patients with CML and Ph+ ALL, with MR3.0 in CML and MR5.0 in Ph+ ALL emerging as favorable prognostic markers. In contrast, the presence of ACAs was associated with shorter survival.
背景:第三代酪氨酸激酶抑制剂Ponatinib已被证明具有抗慢性髓性白血病(CML)和费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)的活性。然而,真实世界的数据,特别是亚洲人口的数据仍然有限。方法:回顾性收集2013年3月至2024年11月台湾地区接受波纳替尼治疗的CML或Ph+ ALL患者。分子和细胞遗传学数据、疗效结局(完全血液学反应[CHR]、分子反应[MR]、无进展生存期[PFS]、总生存期[OS])和不良事件进行了分析。结果:52例患者(27例CML, 25例Ph+ ALL,中位随访:50.7个月)中,94%的患者因复发或难治性疾病接受了波纳替尼治疗。在既往无CHR的患者中,89%在12个月时达到CHR。在没有既往MR的患者中,57%的患者在12个月时MR2.0, 53%的患者MR3.0, 26%的患者MR5.0。6个月时MR2.0和12个月时MR3.0与CML患者预后改善相关。36%的患者发现了额外的染色体异常(ACAs),并与较差的生存率相关,而78%的研究患者(包括T315I(57%))的激酶结构域突变没有影响结果。MR3.0在任何时候预测CML患者有更好的OS和PFS, MR5.0在Ph+ ALL患者有更好的PFS。1例(1.9%)发生动脉闭塞事件。结论:Ponatinib在预处理CML和Ph+ ALL患者中显示出实质性的实际疗效,CML的MR3.0和Ph+ ALL的MR5.0成为有利的预后指标。相反,ACAs的存在与较短的生存期相关。
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引用次数: 0
A Multistakeholder Qualitative Analysis of Barriers to Autologous Stem Cell Transplantation for Multiple Myeloma 多发性骨髓瘤自体干细胞移植障碍的多利益相关者定性分析。
IF 2.7 4区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.07.002
James Fan Wu , Idayat M. Akinola , Anita D’Souza , Rachel Cusatis

Purpose

We investigated autologous stem cell transplantation (ASCT) barriers in a single-center qualitative study by interviewing patients with multiple myeloma (MM), transplant physicians (TPs), and referring physicians (RPs).

Methods

Patients with MM and referred for ASCT evaluation between January 01, 2021 and December 31, 2022, TPs from 2 Wisconsin transplant centers, and RPs from rural and urban Wisconsin were recruited. Interviews were conducted using a semi-structured interview guide focused on ASCT barriers. Transcripts were double-coded and reviewed. An initial codebook with prespecified themes based on the interview guide was developed and iteratively revised.

Results

Eighteen patients, 5 TPs, and 4 RPs were interviewed. Four major ASCT barriers themes were identified across all stakeholders: caregiver support, patient concerns and knowledge, financial toxicity, and logistics. Unique themes included social support by patients and ASCT referral by physicians. Lacking caregiver support was more common among single, childless, and socially/geographically isolated patients. Patients were most concerned about side effects, long hospital stays, and quality of life. Patients used online websites and support groups to gain knowledge and support. While most patients experienced financial toxicity, care costs were rarely discussed. Distance from transplant center, transportation, and care coordination were barriers. Referrals from community oncologists are a major barrier. Patients never seen at a transplant center may have the most barriers.

Conclusion

This qualitative study of both patients and physicians investigating barriers to access to ASCT in MM, provides a much-needed multistakeholder perspective. Interventional strategies targeting key barriers will be critical in improving ASCT utilization in MM.
目的:我们通过采访多发性骨髓瘤(MM)患者、移植医生(tp)和转诊医生(rp),在一项单中心定性研究中调查了自体干细胞移植(ASCT)障碍。方法:招募2021年1月1日至2022年12月31日期间接受ASCT评估的MM患者,来自威斯康星州2个移植中心的TPs,以及威斯康星州农村和城市的RPs。访谈采用半结构化访谈指南,重点关注ASCT障碍。记录被双重编码和审查。根据采访指南编写了一份带有预先指定主题的初始代码本,并进行了反复修订。结果:访谈18例患者,5例TPs, 4例RPs。在所有利益相关者中确定了四个主要的ASCT障碍主题:护理人员支持、患者关注和知识、财务毒性和物流。独特的主题包括患者的社会支持和医生的ASCT转诊。缺乏照顾者支持在单身、无子女和社会/地理隔离的患者中更为常见。患者最关心的是副作用、住院时间和生活质量。患者利用在线网站和支持小组获得知识和支持。虽然大多数患者都经历了经济损失,但很少讨论护理费用。与移植中心的距离、交通和护理协调是障碍。来自社区肿瘤学家的转诊是一个主要障碍。从未在移植中心见过的患者可能面临最大的障碍。结论:这项定性研究调查了MM患者和医生获得ASCT的障碍,提供了急需的多利益相关者视角。针对关键障碍的干预策略对于提高急性粒细胞白血病患者ASCT的利用至关重要。
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引用次数: 0
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Clinical Lymphoma, Myeloma & Leukemia
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