A. Deshane, J. Yahalom, N. A. Wijetunga, A. Kumar, B. Fregonese, A. Zelenetz, G. Salles, B. S. Imber
<p><b>Introduction:</b> The role for radiotherapy (RT) in mantle cell lymphoma (MCL) is limited as MCL often presents in advanced stages. A broader role may be rational given MCL’s propensity for profound but inconsistent radiosensitivity. Common molecular alterations in MCL impact prognosis, namely TP53 mutations (TP53mut). TP53mut can influence systemic therapy choices but its impact on radiosensitivity, or RT decision making is unclear. Better understanding could guide precision radiotherapy.</p><p><b>Methods:</b> We analyzed patients (pts) treated with RT for MCL from 2010 to 2024, focusing on a cohort with next generation sequencing (NGS) for somatic genetic alterations (<i>n</i> = 66). Age and stage at RT, treatment intent, relapsed status, site of RT, and prior systemic therapy were collected. Sites treated in pts with TP53mut versus without TP53mut (TP53wt) were compared. Lesion SUV and diameter, extranodal (EN) status of the treated site, blastoid histology, RT dose, and metabolic response at first assessment were compared. Additionally, sites receiving very low dose radiotherapy (VLDRT, 4 Gy) and sites of local failure (LF) were analyzed.</p><p><b>Results:</b> 66 patients were identified, treated to 97 sites. 84 sites (87%) were treated in the relapsed setting. 54 sites (56%) were localized relapsed or early-stage disease. By site, median follow up after RT was 1.5 years. 61 sites (64%) treated were EN. Median RT dose was 30 Gy (4–40 Gy), median lesion diameter was 3.5 cm (0.9–22 cm), and median SUV max was 7.5 (0–61.6). 80% (<i>n</i> = 77) of sites had available PET response assessment at a median of 1.7 months (0.1–7.1) post-RT. Overall response rate (ORR) was 98.7%, and complete response (CR) rate (CRR) was 81% (<i>n</i> = 62). 32% of pts (<i>n</i> = 21) treated to 33 sites (34%) harbored TP53mut. ORR and CRR were 100% and 83% in TP53wt and 96% and 80% in TP53mut. RT dose (<i>p</i> = 0.817) and CR% (<i>p</i> = 0.491) did not differ by TP53 status. When analyzed by site, TP53mut had significantly worse 1-year FFLP than TP53wt (100 % vs. 85%; <i>p</i> = 0.002). 6 sites overall (6.2%) had LF; of note, 4 of 6 sites received only 4 Gy. TP53mut status was associated with higher risk of LF (<i>p</i> = 0.024). Analysis of sites treated to 4 Gy (<i>n</i> = 14; 14.4%) revealed that TP53mut remained associated with increased risk of LF (<i>p</i> = 0.002). For sites receiving > 4 Gy (<i>n</i> = 83; Median dose 30 Gy, Range 10–40 Gy), presence of TP53mut (<i>n</i> = 30) suggested association with FFLP, though not signficant (<i>p</i> = 0.069). ORR and CRR was 100% and 82% for sites receiving > 4 gy and 89% and 79% for sites receiving VLDRT.</p><p><b>Conclusions:</b> In this cohort of MCL treated with RT, response was excellent, and LF was rare. Most sites of LF received VLDRT. TP53mut was significantly associated with higher risk of LF in sites treated with 4 Gy. Despite excellent responses to RT at higher, definitive doses, sites of pts wi
导言：放射治疗在套细胞淋巴瘤（MCL）中的作用有限，因为MCL通常出现在晚期。鉴于MCL具有深刻但不一致的放射敏感性，更广泛的作用可能是合理的。MCL中常见的影响预后的分子改变，即TP53突变（TP53mut）。TP53mut可以影响全身治疗的选择，但其对放射敏感性或放疗决策的影响尚不清楚。更好的理解可以指导精准放疗。方法：我们分析了2010年至2024年期间接受RT治疗的MCL患者（pts），重点分析了采用下一代测序（NGS）检测体细胞遗传改变的队列（n = 66）。收集年龄和放疗分期、治疗意图、复发状态、放疗部位和既往全身治疗。比较携带TP53mut和不携带TP53mut的患者的治疗部位（TP53wt）。比较病变的SUV和直径、治疗部位的结外（EN）状态、囊胚组织学、RT剂量和首次评估时的代谢反应。此外，还分析了极低剂量放疗（VLDRT, 4 Gy）和局部失败（LF）的部位。结果：确诊66例，治疗97个部位。84个部位（87%）接受了治疗。54个部位（56%）为局部复发或早期疾病。按部位划分，放疗后的中位随访时间为1.5年。61处（64%）为EN。中位放疗剂量为30 Gy (4 ~ 40 Gy)，中位病灶直径为3.5 cm (0.9 ~ 22 cm)，中位SUV max为7.5（0 ~ 61.6）。80% （n = 77）的地点在rt后中位时间为1.7个月（0.1-7.1个月）时进行了PET反应评估。总缓解率（ORR）为98.7%，完全缓解率（CRR）为81% （n = 62）。33个部位（34%）携带TP53mut的患者占32% （n = 21）。TP53wt的ORR和CRR分别为100%和83%，TP53mut的ORR和CRR分别为96%和80%。放疗剂量（p = 0.817）和CR% （p = 0.491）无TP53状态差异。通过位点分析，TP53mut的1年FFLP显著低于TP53wt (100% vs 85%；P = 0.002)。6个站点（6.2%）有LF；值得注意的是，6个地点中有4个只收到4戈瑞。TP53mut状态与LF的高风险相关（p = 0.024）。4 Gy处理部位分析(n = 14；14.4%)显示TP53mut仍与LF风险增加相关（p = 0.002）。对于接收>；4 Gy (n = 83；中位剂量30 Gy，范围10-40 Gy)， TP53mut的存在（n = 30）提示与FFLP相关，但不显著（p = 0.069）。接收>；接受VLDRT的部位分别为89%和79%。结论：在这组接受RT治疗的MCL患者中，疗效非常好，LF罕见。大部分LF部位接受VLDRT。在接受4gy治疗的部位，TP53mut与较高的LF风险显著相关。尽管在更高的确定剂量下对放射治疗有良好的反应，但TP53mut患者的部位对VLDRT的反应可能不太好，这表明相对放射耐药和需要考虑剂量增加或联合治疗策略。关键词：非霍奇金利益冲突潜在来源；顾问或顾问角色：Convergent R. N. R. LtdA。顾问或顾问角色：AstraZeneca， Genentech, Janssen Oncology， Kite pharmaceuticals股权：BridgeBio IncA。顾问或顾问角色：Abbvie， Arvinas Inc, Astrazeneca, BeiGene USA, bright Network LLC, Curio Science, Dava Oncology, Eli Lilly, Genentech, Kite pharmaceuticals。顾问或顾问角色：Abbvie, Aptitude Health, BeiGene USA Inc, Bristol-Myers Squibb, Celgene, Curio Science LLC, Debiopharm， Everest临床研究公司，Fondazione Ferrata Storti, GenMab, Incyte, Innate Pharma, Ipsen Pharma，杨森全球服务有限公司，杨森韩国有限公司，Kite制药，Medscape，默克，MJH生命科学，ModeX Therapeutics，诺华，Nurix, Orna, Practice Point Communications LLC, Research to Practice，罗氏，Scientific Education Support, Treeline biosciences。顾问或顾问角色：GT Medical Technologies Inc， Ono Pharma, Telix Pharmaceuticals Limited
{"title":"THE EFFECT OF TP53 MUTATIONS ON THE LOCAL RESPONSE OF MANTLE CELL LYMPHOMA TO RADIATION THERAPY","authors":"A. Deshane, J. Yahalom, N. A. Wijetunga, A. Kumar, B. Fregonese, A. Zelenetz, G. Salles, B. S. Imber","doi":"10.1002/hon.70094_268","DOIUrl":"https://doi.org/10.1002/hon.70094_268","url":null,"abstract":"<p><b>Introduction:</b> The role for radiotherapy (RT) in mantle cell lymphoma (MCL) is limited as MCL often presents in advanced stages. A broader role may be rational given MCL’s propensity for profound but inconsistent radiosensitivity. Common molecular alterations in MCL impact prognosis, namely TP53 mutations (TP53mut). TP53mut can influence systemic therapy choices but its impact on radiosensitivity, or RT decision making is unclear. Better understanding could guide precision radiotherapy.</p><p><b>Methods:</b> We analyzed patients (pts) treated with RT for MCL from 2010 to 2024, focusing on a cohort with next generation sequencing (NGS) for somatic genetic alterations (<i>n</i> = 66). Age and stage at RT, treatment intent, relapsed status, site of RT, and prior systemic therapy were collected. Sites treated in pts with TP53mut versus without TP53mut (TP53wt) were compared. Lesion SUV and diameter, extranodal (EN) status of the treated site, blastoid histology, RT dose, and metabolic response at first assessment were compared. Additionally, sites receiving very low dose radiotherapy (VLDRT, 4 Gy) and sites of local failure (LF) were analyzed.</p><p><b>Results:</b> 66 patients were identified, treated to 97 sites. 84 sites (87%) were treated in the relapsed setting. 54 sites (56%) were localized relapsed or early-stage disease. By site, median follow up after RT was 1.5 years. 61 sites (64%) treated were EN. Median RT dose was 30 Gy (4–40 Gy), median lesion diameter was 3.5 cm (0.9–22 cm), and median SUV max was 7.5 (0–61.6). 80% (<i>n</i> = 77) of sites had available PET response assessment at a median of 1.7 months (0.1–7.1) post-RT. Overall response rate (ORR) was 98.7%, and complete response (CR) rate (CRR) was 81% (<i>n</i> = 62). 32% of pts (<i>n</i> = 21) treated to 33 sites (34%) harbored TP53mut. ORR and CRR were 100% and 83% in TP53wt and 96% and 80% in TP53mut. RT dose (<i>p</i> = 0.817) and CR% (<i>p</i> = 0.491) did not differ by TP53 status. When analyzed by site, TP53mut had significantly worse 1-year FFLP than TP53wt (100 % vs. 85%; <i>p</i> = 0.002). 6 sites overall (6.2%) had LF; of note, 4 of 6 sites received only 4 Gy. TP53mut status was associated with higher risk of LF (<i>p</i> = 0.024). Analysis of sites treated to 4 Gy (<i>n</i> = 14; 14.4%) revealed that TP53mut remained associated with increased risk of LF (<i>p</i> = 0.002). For sites receiving > 4 Gy (<i>n</i> = 83; Median dose 30 Gy, Range 10–40 Gy), presence of TP53mut (<i>n</i> = 30) suggested association with FFLP, though not signficant (<i>p</i> = 0.069). ORR and CRR was 100% and 82% for sites receiving > 4 gy and 89% and 79% for sites receiving VLDRT.</p><p><b>Conclusions:</b> In this cohort of MCL treated with RT, response was excellent, and LF was rare. Most sites of LF received VLDRT. TP53mut was significantly associated with higher risk of LF in sites treated with 4 Gy. Despite excellent responses to RT at higher, definitive doses, sites of pts wi","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Cramer, O. Al-Sawaf, E. Görgen, L. Mazot, S. Robrecht, M. Schüler-Aparicio, C. Paulitschek, A. Zey, A. Albrecht, J. Blau, L. Jung, S. Reidel, F. Bosch, C. da Cuna Bang, M. Doubek, E. Feyzi, A. Fink, P. Ghia, M. Gregor, R. Guieze, K. Jamroziak, A. Janssens, A. P. Kater, S. Kersting, P. Langerbeins, M. Levin, V. Lindström, M. Mattsson, C. Niemann, A. Quinquenel, M. Ritgen, L. Scarfò, P. Staber, S. Stilgenbauer, T. Tadmor, P. Thornton, E. Tausch, L. Ysebaert, K. Fischer, B. F. Eichhorst, M. Hallek
<p><b>Background:</b> The two major options for the first-line therapy of chronic lymphocytic leukemia (CLL) are a continuous BTK inhibitor treatment given as long as possible for disease control, or a venetoclax-based fixed-duration treatment, which usually leads to deep responses and a treatment-free interval of several years. There is an increased use of fixed-duration venetoclax-based regimens, such as venetoclax plus obinutuzumab (12 cycles) or venetoclax plus ibrutinib or acalabrutinib with/without obinutuzumab. While these combination therapies are more intense compared to monotherapies, the treatment-free interval carries advantages in terms of quality of life, safety and costs. The goal of this phase-III trial is to evaluate if a more individualized, but time-limited treatment duration is beneficial.</p><p><b>Methods:</b> Two treatment arms have a fixed-duration and one arm evaluates a treatment duration based on measurable residual disease (MRD):</p><p>— the standard arm A is the established combination of venetoclax and obinutuzumab (Ven-Obi, 12 cycles with a duration of 28 days, Obi only during cycles 1–6),</p><p>— arm B evaluates venetoclax plus pirtobrutinib (Ven-Pirto) for 15 cycles (3 cycles pirtobrutinib alone, then 12 cycles combined with venetoclax), and</p><p>— in arm C, Ven-Pirto will be administered for at least 15 and up to 36 cycles (as long as there is a deepening of response) until achievement of undetectable MRD (uMRD). To facilitate the transfer to clinical routine, MRD is measured in peripheral blood, by multi-colour flow cytometry and with a cut-off of 10<sup>−4</sup>. Two MRD assessments with an interval of 12 weeks both documenting uMRD are needed to allow for a treatment discontinuation and treatment will be continued for an additional 12 weeks after the second uMRD result as a consolidation.</p><p>813 patients with previously untreated CLL/SLL irrespective of age, comorbidities or CLL risk-factors will be recruited 1:1:1 to the three arms (271 each) with a stratification according to TP53 deletion and/or mutation, IGHV mutational status, disease type (CLL vs. SLL), and age. The primary endpoint is the investigator-assessed progression-free survival (PFS). The trial is designed to show both superiority of MRD-guided Ven-Pirto over Ven-Obi and over fixed duration Ven-Pirto. Secondary endpoints include iwCLL response, MRD, overall survival and safety parameters.</p><p><b>Results:</b> Recruitment is expected to start at the time of the ICML meeting. The estimated recruitment time of the 813 patients in approximately 160 sites in 16 countries is 20 months. Approximately 41 months after start of recruitment, a sufficient number of PFS events shall be reached for the primary endpoint analysis.</p><p><b>Summary/Conclusion:</b> The CLL18/MOIRAI trial will address the question whether an individualized, MRD-guided first-line treatment with pirtobrutinib and venetoclax improves the outcome of patients with CLL/SLL compared
{"title":"CLL18/MOIRAI TRIAL AIMING TO ESTABLISH MEASUREMENT OF INDIVIDUAL RESIDUAL DISEASE FOR ADJUSTMENT OF TREATMENT DURATION TO IMPROVE OUTCOMES IN TREATMENT-NAIVE CLL/SLL","authors":"P. Cramer, O. Al-Sawaf, E. Görgen, L. Mazot, S. Robrecht, M. Schüler-Aparicio, C. Paulitschek, A. Zey, A. Albrecht, J. Blau, L. Jung, S. Reidel, F. Bosch, C. da Cuna Bang, M. Doubek, E. Feyzi, A. Fink, P. Ghia, M. Gregor, R. Guieze, K. Jamroziak, A. Janssens, A. P. Kater, S. Kersting, P. Langerbeins, M. Levin, V. Lindström, M. Mattsson, C. Niemann, A. Quinquenel, M. Ritgen, L. Scarfò, P. Staber, S. Stilgenbauer, T. Tadmor, P. Thornton, E. Tausch, L. Ysebaert, K. Fischer, B. F. Eichhorst, M. Hallek","doi":"10.1002/hon.70093_OT02","DOIUrl":"https://doi.org/10.1002/hon.70093_OT02","url":null,"abstract":"<p><b>Background:</b> The two major options for the first-line therapy of chronic lymphocytic leukemia (CLL) are a continuous BTK inhibitor treatment given as long as possible for disease control, or a venetoclax-based fixed-duration treatment, which usually leads to deep responses and a treatment-free interval of several years. There is an increased use of fixed-duration venetoclax-based regimens, such as venetoclax plus obinutuzumab (12 cycles) or venetoclax plus ibrutinib or acalabrutinib with/without obinutuzumab. While these combination therapies are more intense compared to monotherapies, the treatment-free interval carries advantages in terms of quality of life, safety and costs. The goal of this phase-III trial is to evaluate if a more individualized, but time-limited treatment duration is beneficial.</p><p><b>Methods:</b> Two treatment arms have a fixed-duration and one arm evaluates a treatment duration based on measurable residual disease (MRD):</p><p>— the standard arm A is the established combination of venetoclax and obinutuzumab (Ven-Obi, 12 cycles with a duration of 28 days, Obi only during cycles 1–6),</p><p>— arm B evaluates venetoclax plus pirtobrutinib (Ven-Pirto) for 15 cycles (3 cycles pirtobrutinib alone, then 12 cycles combined with venetoclax), and</p><p>— in arm C, Ven-Pirto will be administered for at least 15 and up to 36 cycles (as long as there is a deepening of response) until achievement of undetectable MRD (uMRD). To facilitate the transfer to clinical routine, MRD is measured in peripheral blood, by multi-colour flow cytometry and with a cut-off of 10<sup>−4</sup>. Two MRD assessments with an interval of 12 weeks both documenting uMRD are needed to allow for a treatment discontinuation and treatment will be continued for an additional 12 weeks after the second uMRD result as a consolidation.</p><p>813 patients with previously untreated CLL/SLL irrespective of age, comorbidities or CLL risk-factors will be recruited 1:1:1 to the three arms (271 each) with a stratification according to TP53 deletion and/or mutation, IGHV mutational status, disease type (CLL vs. SLL), and age. The primary endpoint is the investigator-assessed progression-free survival (PFS). The trial is designed to show both superiority of MRD-guided Ven-Pirto over Ven-Obi and over fixed duration Ven-Pirto. Secondary endpoints include iwCLL response, MRD, overall survival and safety parameters.</p><p><b>Results:</b> Recruitment is expected to start at the time of the ICML meeting. The estimated recruitment time of the 813 patients in approximately 160 sites in 16 countries is 20 months. Approximately 41 months after start of recruitment, a sufficient number of PFS events shall be reached for the primary endpoint analysis.</p><p><b>Summary/Conclusion:</b> The CLL18/MOIRAI trial will address the question whether an individualized, MRD-guided first-line treatment with pirtobrutinib and venetoclax improves the outcome of patients with CLL/SLL compared ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_OT02","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Dedieu, H. Chanvrier, J. Carr-Klappert, A. Batista Mesquita Sauvage, S. Manciana, B. Van Meenen, M. Cote, T. Corbière, H. Auner, F. Solly, M. Eicher
<p>C. Dedieu, H. Chanvrier, and F. Solly equally contributing author.</p><p><b>Introduction:</b> Patients with hematological diseases, including blood cancers such as lymphoma or myeloma, often face significant difficulties in navigating health information about their illness due to the complexity of these conditions.</p><p>One of the self-reported educational needs of patients with hematological cancer is receiving clear and comprehensive information about laboratory results. Although these patients often undergo procedures such as venipuncture, knowledge gaps regarding laboratory results and biological concepts have been highlighted.</p><p>However, repeated procedures in combination with knowledge gaps and lack of information tailoring regarding laboratory results can decrease patient adherence and increase anxiety.</p><p>Our aim is to assess hematology patients’ knowledge of laboratory results and biological concepts, and their educational needs (format and frequency). We are also investigating patients’ interest in a novel biomedical consultation.</p><p><b>Methods:</b> This cross-sectional study is based on a digital self-reported questionnaire. Inpatients and outpatients over 18 years of age with a hematological disease and their caregivers are recruited at the Lausanne University Hospital by direct approach, flyers, patient associations or mail. The sample size of 103 was determined using Cochran’s formula, referencing a similar study. The questionnaire is divided into four sections consisting of (i) demographic information, (ii) general health literacy and disease awareness, (iii) preferences for educational interventions, and (iv) patient self-efficacy in managing laboratory results/biomedical information.</p><p><b>Results:</b> Preliminary results were obtained from 36 patients between November and December 2024. The largest group of participants were aged 60–75 years (42%), followed by those aged 75 years or older (25%). Patients with lymphoma and myeloma represented 5.6% and 22% of the participants respectively. Most participants (56%) rated their knowledge of biological concepts as average or poor. Only 19% of participants reported having a good understanding of blood counts. Understanding technical language and the meaning of laboratory results for their health was challenging according to 69%. Most participants (67%) expressed a desire to receive additional information regarding their laboratory results while 50% were interested in an individual educational biomedical consultation about laboratory analyses.</p><p><b>Conclusion:</b> These preliminary results provide valuable insights into patients' knowledge, unmet educational needs and preferences regarding educational formats. Recruitment is still ongoing, and we aim to present the final results at the conference. Our study will ultimately contribute to the development of an educational intervention to improve patients’ knowledge and self-management of laboratory results. Further st
C. Dedieu， H. Chanvrier和F. Solly都是贡献作者。导读：血液学疾病患者，包括血癌如淋巴瘤或骨髓瘤，由于这些疾病的复杂性，在浏览有关其疾病的健康信息时经常面临重大困难。血液病患者自我报告的教育需求之一是获得关于实验室结果的清晰和全面的信息。虽然这些患者经常接受诸如静脉穿刺之类的手术，但关于实验室结果和生物学概念的知识差距已经突出。然而，重复的程序加上知识差距和缺乏关于实验室结果的信息定制可能会降低患者的依从性并增加焦虑。我们的目的是评估血液病患者对实验室结果和生物学概念的知识，以及他们的教育需求（格式和频率）。我们也在调查患者对新型生物医学咨询的兴趣。方法：本横断面研究基于数字自我报告问卷。洛桑大学医院通过直接接触、传单、患者协会或邮件等方式招募18岁以上的血液病住院和门诊患者及其护理人员。103个样本的大小是根据科克伦公式确定的，参考了一个类似的研究。问卷分为四个部分，包括：(i)人口统计信息，（ii）一般卫生知识和疾病意识，（iii）对教育干预措施的偏好，以及（iv）患者在管理实验室结果/生物医学信息方面的自我效能。结果：2024年11 - 12月36例患者获得初步结果。最大的参与者群体是60-75岁（42%），其次是75岁及以上的人（25%）。淋巴瘤和骨髓瘤患者分别占参与者的5.6%和22%。大多数参与者（56%）认为他们对生物学概念的了解一般或较差。只有19%的参与者报告对血液计数有很好的了解。69%的人表示，理解技术语言和实验室结果对其健康的意义具有挑战性。大多数参与者（67%）表示希望获得有关其实验室结果的额外信息，而50%的人对有关实验室分析的个人教育生物医学咨询感兴趣。结论：这些初步结果为了解患者的知识、未满足的教育需求和对教育形式的偏好提供了有价值的见解。招聘仍在进行中，我们的目标是在会议上公布最终结果。我们的研究最终将有助于教育干预的发展，以提高患者对实验室结果的知识和自我管理。进一步的步骤将是使干预措施适应患者的特点，以提供个性化的、量身定制的教育支持。关键词：以病人和家庭为中心的护理潜在的利益冲突来源：M。顾问或顾问角色：ME所在机构因其在咨询委员会的活动而获得罗氏公司的报酬。其他报酬：ME所在机构因其在罗氏、BMS和Vifor的演讲和讲座而获得报酬
{"title":"EDUCATIONAL NEEDS OF SWISS PATIENTS WITH HEMATOLOGICAL DISEASES: FOCUS ON KNOWLEDGE REGARDING HEMATOLOGY LABORATORY RESULTS AND BIOMEDICAL CONCEPTS","authors":"C. Dedieu, H. Chanvrier, J. Carr-Klappert, A. Batista Mesquita Sauvage, S. Manciana, B. Van Meenen, M. Cote, T. Corbière, H. Auner, F. Solly, M. Eicher","doi":"10.1002/hon.70093_ON08","DOIUrl":"https://doi.org/10.1002/hon.70093_ON08","url":null,"abstract":"<p>C. Dedieu, H. Chanvrier, and F. Solly equally contributing author.</p><p><b>Introduction:</b> Patients with hematological diseases, including blood cancers such as lymphoma or myeloma, often face significant difficulties in navigating health information about their illness due to the complexity of these conditions.</p><p>One of the self-reported educational needs of patients with hematological cancer is receiving clear and comprehensive information about laboratory results. Although these patients often undergo procedures such as venipuncture, knowledge gaps regarding laboratory results and biological concepts have been highlighted.</p><p>However, repeated procedures in combination with knowledge gaps and lack of information tailoring regarding laboratory results can decrease patient adherence and increase anxiety.</p><p>Our aim is to assess hematology patients’ knowledge of laboratory results and biological concepts, and their educational needs (format and frequency). We are also investigating patients’ interest in a novel biomedical consultation.</p><p><b>Methods:</b> This cross-sectional study is based on a digital self-reported questionnaire. Inpatients and outpatients over 18 years of age with a hematological disease and their caregivers are recruited at the Lausanne University Hospital by direct approach, flyers, patient associations or mail. The sample size of 103 was determined using Cochran’s formula, referencing a similar study. The questionnaire is divided into four sections consisting of (i) demographic information, (ii) general health literacy and disease awareness, (iii) preferences for educational interventions, and (iv) patient self-efficacy in managing laboratory results/biomedical information.</p><p><b>Results:</b> Preliminary results were obtained from 36 patients between November and December 2024. The largest group of participants were aged 60–75 years (42%), followed by those aged 75 years or older (25%). Patients with lymphoma and myeloma represented 5.6% and 22% of the participants respectively. Most participants (56%) rated their knowledge of biological concepts as average or poor. Only 19% of participants reported having a good understanding of blood counts. Understanding technical language and the meaning of laboratory results for their health was challenging according to 69%. Most participants (67%) expressed a desire to receive additional information regarding their laboratory results while 50% were interested in an individual educational biomedical consultation about laboratory analyses.</p><p><b>Conclusion:</b> These preliminary results provide valuable insights into patients' knowledge, unmet educational needs and preferences regarding educational formats. Recruitment is still ongoing, and we aim to present the final results at the conference. Our study will ultimately contribute to the development of an educational intervention to improve patients’ knowledge and self-management of laboratory results. Further st","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_ON08","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Piffaretti, I. Romano, J. Marquez de Almeida, M. Salehi, H. Javanmard Khameneh, R. Moia, A. Bruscaggin, F. Jauk, S. Bocchetta, A. Condoluci, G. Forestieri, M. C. Pirosa, L. Terzi di Bergamo, S. Schär, A. Zenobi, A. Stathis, S. Monticelli, G. Gaidano, G. Guarda, D. Rossi
<p>D. Piffaretti and I. Romano equally contributing authors.</p><p><b>Introduction:</b> Clonal Hematopoiesis (CH) may promote diffuse large B-cell lymphoma (DLBCL) in two ways: by seeding mutations in the B-cells progenitors, potentially contributing to malignant transformation. Alternatively, lymphoma may be promoted by the clonal and pro-inflammatory tumor microenvironment derived from CH. In this study we aimed to determine: (i) CH prevalence in newly diagnosed DLBCL; (ii) clinical impact of CH; (iii) correlation between CH and DLBCL genetic lesions; (iv) co-occurrence frequency of DLBCL driver and CH mutations at the single cell level; (v) enrichment of CH in cells of the lymphoma microenvironment compared to blood.</p><p><b>Methods:</b> Patients (<i>n</i> = 387) from the IOSI-EMA003 and SAKK38/19 trials were analyzed. CH mutations were identified in genomic DNA using a myeloid panel, while a lymphoid panel detected DLBCL mutations, somatic copy number abnormalities, and <i>BCL6</i> fusions in plasma cfDNA. Multiomic scDNA-seq and immunophenotyping of paired peripheral blood (PB) or bone marrow (BM) and disaggregated lymph nodes of 6 patients were performed. A custom Tapestri (MissionBio) panel targeted CH mutations and barcoded the dominant DLBCL clone by covering trunk oncogene mutations, enabling simultaneous genotyping and phenotyping of B cells, T cell subtypes, and myeloid cells. To assess whether CH-bearing myeloid cells support DLBCL in vitro: (i) BM cells from <i>Tet2</i> knockout (KO) and control mice were differentiated into macrophages and co-cultured with a <i>Tp53</i> KO murine B-cell lymphoma line; (ii) biallelic <i>TET2-</i>KO human THP1 monocytic cells, were differentiated into macrophages and co-cultured with DLBCL cell lines. Additionally, lymphoma-prone <i>Klf2</i><sup><i>fl/fl</i></sup><i>/Notch2IC</i><sup><i>fl/+</i></sup><i>/Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd</i>45<i>.2</i><sup>+/+</sup> oncogenic and <i>Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd45.2</i><sup>+/−</sup> control mice were adoptively transplanted with BM cells from <i>Tet</i>2<sup>+/+</sup>, <i>Tet</i>2<sup>+/−</sup>, and <i>Tet2</i><sup>−/−</sup> C57BL/6 <i>Cd45.1</i><sup>+/−</sup> mice without conditioning.</p><p><b>Results:</b> The analysis was done including patients per the CONSORT diagram (Figure 1A). CH mutations (VAF > 1%) were found in 38% of patients, primarily in <i>DNMT3A</i> and <i>TET2</i>, and correlated with age (Figure 1B). However, CH showed no association with features of lymphoma aggressiveness (clinical stage, B-symptoms, IPI) or DLBCL subtypes (cell of origin, C1-C5). Cox analyses (univariate/multivariate, adjusted for IPI), revealed no impact of CH on progression-free survival or lymphoma-specific survival. In vitro, lymphoma cell survival was limitedly affected by <i>TET2</i> status in macrophages. Engraftment in control mice mirrored the typical load of CH in humans (∼1% PB leukocytes at 3 months), whereas <i>Tet</i>2<sup>+/−</su
{"title":"CLONAL HEMATOPOIESIS IN DIFFUSE LARGE B-CELL LYMPHOMA","authors":"D. Piffaretti, I. Romano, J. Marquez de Almeida, M. Salehi, H. Javanmard Khameneh, R. Moia, A. Bruscaggin, F. Jauk, S. Bocchetta, A. Condoluci, G. Forestieri, M. C. Pirosa, L. Terzi di Bergamo, S. Schär, A. Zenobi, A. Stathis, S. Monticelli, G. Gaidano, G. Guarda, D. Rossi","doi":"10.1002/hon.70093_60","DOIUrl":"https://doi.org/10.1002/hon.70093_60","url":null,"abstract":"<p>D. Piffaretti and I. Romano equally contributing authors.</p><p><b>Introduction:</b> Clonal Hematopoiesis (CH) may promote diffuse large B-cell lymphoma (DLBCL) in two ways: by seeding mutations in the B-cells progenitors, potentially contributing to malignant transformation. Alternatively, lymphoma may be promoted by the clonal and pro-inflammatory tumor microenvironment derived from CH. In this study we aimed to determine: (i) CH prevalence in newly diagnosed DLBCL; (ii) clinical impact of CH; (iii) correlation between CH and DLBCL genetic lesions; (iv) co-occurrence frequency of DLBCL driver and CH mutations at the single cell level; (v) enrichment of CH in cells of the lymphoma microenvironment compared to blood.</p><p><b>Methods:</b> Patients (<i>n</i> = 387) from the IOSI-EMA003 and SAKK38/19 trials were analyzed. CH mutations were identified in genomic DNA using a myeloid panel, while a lymphoid panel detected DLBCL mutations, somatic copy number abnormalities, and <i>BCL6</i> fusions in plasma cfDNA. Multiomic scDNA-seq and immunophenotyping of paired peripheral blood (PB) or bone marrow (BM) and disaggregated lymph nodes of 6 patients were performed. A custom Tapestri (MissionBio) panel targeted CH mutations and barcoded the dominant DLBCL clone by covering trunk oncogene mutations, enabling simultaneous genotyping and phenotyping of B cells, T cell subtypes, and myeloid cells. To assess whether CH-bearing myeloid cells support DLBCL in vitro: (i) BM cells from <i>Tet2</i> knockout (KO) and control mice were differentiated into macrophages and co-cultured with a <i>Tp53</i> KO murine B-cell lymphoma line; (ii) biallelic <i>TET2-</i>KO human THP1 monocytic cells, were differentiated into macrophages and co-cultured with DLBCL cell lines. Additionally, lymphoma-prone <i>Klf2</i><sup><i>fl/fl</i></sup><i>/Notch2IC</i><sup><i>fl/+</i></sup><i>/Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd</i>45<i>.2</i><sup>+/+</sup> oncogenic and <i>Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd45.2</i><sup>+/−</sup> control mice were adoptively transplanted with BM cells from <i>Tet</i>2<sup>+/+</sup>, <i>Tet</i>2<sup>+/−</sup>, and <i>Tet2</i><sup>−/−</sup> C57BL/6 <i>Cd45.1</i><sup>+/−</sup> mice without conditioning.</p><p><b>Results:</b> The analysis was done including patients per the CONSORT diagram (Figure 1A). CH mutations (VAF > 1%) were found in 38% of patients, primarily in <i>DNMT3A</i> and <i>TET2</i>, and correlated with age (Figure 1B). However, CH showed no association with features of lymphoma aggressiveness (clinical stage, B-symptoms, IPI) or DLBCL subtypes (cell of origin, C1-C5). Cox analyses (univariate/multivariate, adjusted for IPI), revealed no impact of CH on progression-free survival or lymphoma-specific survival. In vitro, lymphoma cell survival was limitedly affected by <i>TET2</i> status in macrophages. Engraftment in control mice mirrored the typical load of CH in humans (∼1% PB leukocytes at 3 months), whereas <i>Tet</i>2<sup>+/−</su","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_60","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu, P. Xu, M. Cai, H. Yang, J. Xiong, Y. Wang, Y. Huang, J. Zhao, H. Yang, J. Chen, L. Wang, S. Luminari, E. Zucca, F. Cavalli, Z. Li, W. Zhao
<p>H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu Z. Li, and W. Zhao equally contributing authors.</p><p><b>Introduction:</b> Natural killer/T-cell lymphoma (NKTCL) is highly aggressive and characterized by Epstein-Barr virus (EBV) infection and overexpression of immune checkpoints. The therapeutic options were limited for patients unsuitable for chemotherapy. Immune checkpoint inhibitors have been shown effective in refractory and relapsed NKTCL. This study aims to investigate the efficacy and safety of programmed death 1 (PD-1) antibody pembrolizumab concurrent with radiotherapy as a first-line treatment in newly diagnosed early-stage frail NKTCL patients.</p><p><b>Methods:</b> This is a multicenter phase II study. Eligible patients met the following criteria: (1) age ≥ 18 years; (2) newly diagnosed NKTCL with Ann Arbor stage I-II disease; (3) presence of at least one risk factor (age > 60 years, elevated serum lactate dehydrogenase, Ann Arbor stage II or primary tumor invasion); (4) unsuitable for systemic chemotherapy. All patients received induction treatment with pembrolizumab (200 mg intravenously on day 1 in each 21-day cycle for 6 cycles) concurrently with radiotherapy (a total dose of 50–54 Gy). The patients achieved complete remission (CR), partial remission (PR), or stable disease (SD) have been given pembrolizumab 200 mg every 21 days as a maintenance up to 2 years. The primary endpoint was 2-year progression-free survival (PFS) rate. The main secondary endpoints included CR rate (CRR), overall response rate (ORR), adverse events and plasma EBV DNA change.</p><p><b>Results:</b> From August 2020 to January 2025, a total of 30 patients with median age of 62 (20–74) years were enrolled in Shanghai Ruijin Hospital and Guangzhou Sun Yat Sen University Cancer Center. All patients were intermediate (60%, <i>n</i> = 18) and high (40%, <i>n</i> = 12) risk according to nomogram-revised risk index. Until February 2025, 62.5% CRR (95% CI: 40.6%–81.2%) and 91.7% ORR (95% CI: 73.0%–99.0%) have been achieved in twenty-four evaluable patients after induction treatment. With median follow-up time of 10.2 months (not yet mature for the analysis of the primary endpoint), the best CRR and ORR were 83.3% (95% CI: 62.6%–95.3%) and 91.7% (95% CI: 73.0%%–99.0%), respectively (Figure). The responses improved with the increase of cycles. The most common adverse events were lymphocytopenia, leukopenia, oral mucositis, radiodermatitis and dry mouth. Grade 3/4 adverse events were low, including lymphocytopenia (16.6%) and oral mucositis (13.3%). The treatment was well-tolerated. Among patients who were EBV DNA positive before treatment, 70% achieved EBV DNA negativity following induction therapy.</p><p><b>Conclusion:</b> Pembrolizumab concurrent with radiotherapy was effective and safe in newly diagnosed early-stage frail NKTCL patients, even in those with intermediate or high risk. Immune checkpoint inhibitors could be applied as first-line alternative
{"title":"A PHASE II TRIAL OF PEMBROLIZUMAB CONCURRENT WITH RADIOTHERAPY FOR FRAIL PATIENTS WITH NEWLY DIAGNOSED EARLY-STAGE NATURAL KILLER/T-CELL LYMPHOMA (IELSG50)","authors":"H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu, P. Xu, M. Cai, H. Yang, J. Xiong, Y. Wang, Y. Huang, J. Zhao, H. Yang, J. Chen, L. Wang, S. Luminari, E. Zucca, F. Cavalli, Z. Li, W. Zhao","doi":"10.1002/hon.70093_62","DOIUrl":"https://doi.org/10.1002/hon.70093_62","url":null,"abstract":"<p>H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu Z. Li, and W. Zhao equally contributing authors.</p><p><b>Introduction:</b> Natural killer/T-cell lymphoma (NKTCL) is highly aggressive and characterized by Epstein-Barr virus (EBV) infection and overexpression of immune checkpoints. The therapeutic options were limited for patients unsuitable for chemotherapy. Immune checkpoint inhibitors have been shown effective in refractory and relapsed NKTCL. This study aims to investigate the efficacy and safety of programmed death 1 (PD-1) antibody pembrolizumab concurrent with radiotherapy as a first-line treatment in newly diagnosed early-stage frail NKTCL patients.</p><p><b>Methods:</b> This is a multicenter phase II study. Eligible patients met the following criteria: (1) age ≥ 18 years; (2) newly diagnosed NKTCL with Ann Arbor stage I-II disease; (3) presence of at least one risk factor (age > 60 years, elevated serum lactate dehydrogenase, Ann Arbor stage II or primary tumor invasion); (4) unsuitable for systemic chemotherapy. All patients received induction treatment with pembrolizumab (200 mg intravenously on day 1 in each 21-day cycle for 6 cycles) concurrently with radiotherapy (a total dose of 50–54 Gy). The patients achieved complete remission (CR), partial remission (PR), or stable disease (SD) have been given pembrolizumab 200 mg every 21 days as a maintenance up to 2 years. The primary endpoint was 2-year progression-free survival (PFS) rate. The main secondary endpoints included CR rate (CRR), overall response rate (ORR), adverse events and plasma EBV DNA change.</p><p><b>Results:</b> From August 2020 to January 2025, a total of 30 patients with median age of 62 (20–74) years were enrolled in Shanghai Ruijin Hospital and Guangzhou Sun Yat Sen University Cancer Center. All patients were intermediate (60%, <i>n</i> = 18) and high (40%, <i>n</i> = 12) risk according to nomogram-revised risk index. Until February 2025, 62.5% CRR (95% CI: 40.6%–81.2%) and 91.7% ORR (95% CI: 73.0%–99.0%) have been achieved in twenty-four evaluable patients after induction treatment. With median follow-up time of 10.2 months (not yet mature for the analysis of the primary endpoint), the best CRR and ORR were 83.3% (95% CI: 62.6%–95.3%) and 91.7% (95% CI: 73.0%%–99.0%), respectively (Figure). The responses improved with the increase of cycles. The most common adverse events were lymphocytopenia, leukopenia, oral mucositis, radiodermatitis and dry mouth. Grade 3/4 adverse events were low, including lymphocytopenia (16.6%) and oral mucositis (13.3%). The treatment was well-tolerated. Among patients who were EBV DNA positive before treatment, 70% achieved EBV DNA negativity following induction therapy.</p><p><b>Conclusion:</b> Pembrolizumab concurrent with radiotherapy was effective and safe in newly diagnosed early-stage frail NKTCL patients, even in those with intermediate or high risk. Immune checkpoint inhibitors could be applied as first-line alternative ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Li, L. Jin, Y. Duan, W. Liu, J. Zhou, F. Li, X. Yang, Y. Jia, K. Yang, Y. Liu, Y. Dai, L. Yang, A. Liu, P. Wu, R. Liu, L. Jiang, X. Yuan, J. Jiang, S. Zhuang, J. Wang, Z. Xu, H. Gao, Q. Zheng, Y. Zhang
<p>Y. Li, L. Jin, Q. Zheng, and Y. Zhang equally contributing authors.</p><p><b>Introduction:</b> T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive malignancy with a high incidence among children and adolescents. Despite its prevalence, research on fusion genes in T-LBL, particularly their distribution and prognostic implications, remains limited. This study aimed to elucidate the frequency of fusion genes in Chinese pediatric T-LBL patients and explore their potential impact on prognosis, thereby providing new insights for clinical management.</p><p><b>Methods:</b> We collected data from 552 pediatric T-LBL patients (aged ≤ 16 years) treated at multiple centers of the China Network of Childhood Lymphoma (CNCL), with fusion gene testing results available for 180 patients. Sequencing-based methods were used to detect fusion genes, and statistical analysis was performed to investigate their associations with patient clinical outcomes.</p><p><b>Results:</b> Among the 180 patients analyzed, 105 (58.3%) were found to harbor fusion genes, with a total of 40 distinct fusion genes identified. The higher percentage of fusion genes were <i>SIL</i>::<i>TAL1</i> (<i>n</i> = 40, 22.2%), <i>MLL</i> fusions (<i>n</i> = 20, 11.1%), <i>TCR</i> partner-related fusions (<i>n</i> = 11, 6.1%), <i>ABL1</i> fusions (<i>n</i> = 9, 5%), <i>NOTCH1</i> fusions (<i>n</i> = 7, 3.9%), and <i>SET</i>::<i>CAN</i> (<i>n</i> = 7, 3.9%) (Figure 1a). These findings highlight the genetic heterogeneity of T-LBL in pediatric patients.</p><p>Prognostic analysis revealed that patients with <i>NOTCH1</i> fusions had significantly poorer event-free survival (EFS) and overall survival (OS) compared to those without <i>NOTCH1</i> fusions (EFS, <i>p</i> < 0.0001; OS, <i>p</i> = 0.00013, Figure 1b,c). The identified <i>NOTCH1</i> fusion types included <i>IKZF2</i>::<i>NOTCH1</i> (<i>n</i> = 4, 57%), <i>MIR142</i>::<i>NOTCH1</i> (<i>n</i> = 2, 29%) and <i>IKZF1</i>::<i>NOTCH1</i> (<i>n</i> = 1, 14%), all of which are associated with poor outcomes. We further analyzed the relationship between <i>NOTCH1</i> mutations and <i>NOTCH1</i> fusions, and there was no obvious evidence of co-occurrence or mutual exclusivity between these genetic events. Notably, although <i>NOTCH1</i> mutations are generally associated with favorable outcomes in pediatric T-LBL patients, the cooccurrence of <i>NOTCH1</i> fusions appeared to diminish this benefit, showing a trend toward poorer prognosis (<i>p</i> = 0.056). These findings indicate that <i>NOTCH1</i> fusions may serve as potential biomarkers for adverse prognosis in pediatric patients with T-LBL. Additionally, <i>SIL::TAL1</i> and <i>MLL</i> fusions were observed but showed no prognostic significance in this cohort, warranting further study in larger cohorts.</p><p><b>Conclusion:</b> Our study provides the comprehensive overview of fusion gene distribution in Chinese pediatric T-LBL patients and highlights the significant prognostic impact of
{"title":"FREQUENCY OF FUSION GENES AND THEIR CLINICAL IMPACTS IN CHINESE PEDIATRIC PATIENTS WITH T-CELL LYMPHOBLASTIC LYMPHOMA","authors":"Y. Li, L. Jin, Y. Duan, W. Liu, J. Zhou, F. Li, X. Yang, Y. Jia, K. Yang, Y. Liu, Y. Dai, L. Yang, A. Liu, P. Wu, R. Liu, L. Jiang, X. Yuan, J. Jiang, S. Zhuang, J. Wang, Z. Xu, H. Gao, Q. Zheng, Y. Zhang","doi":"10.1002/hon.70093_36","DOIUrl":"https://doi.org/10.1002/hon.70093_36","url":null,"abstract":"<p>Y. Li, L. Jin, Q. Zheng, and Y. Zhang equally contributing authors.</p><p><b>Introduction:</b> T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive malignancy with a high incidence among children and adolescents. Despite its prevalence, research on fusion genes in T-LBL, particularly their distribution and prognostic implications, remains limited. This study aimed to elucidate the frequency of fusion genes in Chinese pediatric T-LBL patients and explore their potential impact on prognosis, thereby providing new insights for clinical management.</p><p><b>Methods:</b> We collected data from 552 pediatric T-LBL patients (aged ≤ 16 years) treated at multiple centers of the China Network of Childhood Lymphoma (CNCL), with fusion gene testing results available for 180 patients. Sequencing-based methods were used to detect fusion genes, and statistical analysis was performed to investigate their associations with patient clinical outcomes.</p><p><b>Results:</b> Among the 180 patients analyzed, 105 (58.3%) were found to harbor fusion genes, with a total of 40 distinct fusion genes identified. The higher percentage of fusion genes were <i>SIL</i>::<i>TAL1</i> (<i>n</i> = 40, 22.2%), <i>MLL</i> fusions (<i>n</i> = 20, 11.1%), <i>TCR</i> partner-related fusions (<i>n</i> = 11, 6.1%), <i>ABL1</i> fusions (<i>n</i> = 9, 5%), <i>NOTCH1</i> fusions (<i>n</i> = 7, 3.9%), and <i>SET</i>::<i>CAN</i> (<i>n</i> = 7, 3.9%) (Figure 1a). These findings highlight the genetic heterogeneity of T-LBL in pediatric patients.</p><p>Prognostic analysis revealed that patients with <i>NOTCH1</i> fusions had significantly poorer event-free survival (EFS) and overall survival (OS) compared to those without <i>NOTCH1</i> fusions (EFS, <i>p</i> < 0.0001; OS, <i>p</i> = 0.00013, Figure 1b,c). The identified <i>NOTCH1</i> fusion types included <i>IKZF2</i>::<i>NOTCH1</i> (<i>n</i> = 4, 57%), <i>MIR142</i>::<i>NOTCH1</i> (<i>n</i> = 2, 29%) and <i>IKZF1</i>::<i>NOTCH1</i> (<i>n</i> = 1, 14%), all of which are associated with poor outcomes. We further analyzed the relationship between <i>NOTCH1</i> mutations and <i>NOTCH1</i> fusions, and there was no obvious evidence of co-occurrence or mutual exclusivity between these genetic events. Notably, although <i>NOTCH1</i> mutations are generally associated with favorable outcomes in pediatric T-LBL patients, the cooccurrence of <i>NOTCH1</i> fusions appeared to diminish this benefit, showing a trend toward poorer prognosis (<i>p</i> = 0.056). These findings indicate that <i>NOTCH1</i> fusions may serve as potential biomarkers for adverse prognosis in pediatric patients with T-LBL. Additionally, <i>SIL::TAL1</i> and <i>MLL</i> fusions were observed but showed no prognostic significance in this cohort, warranting further study in larger cohorts.</p><p><b>Conclusion:</b> Our study provides the comprehensive overview of fusion gene distribution in Chinese pediatric T-LBL patients and highlights the significant prognostic impact of ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. S. Tam, P. Ghia, M. Shadman, T. Munir, S. S. Opat, P. A. Walker, M. Lasica, I. W. Flinn, T. Tian, S. Agresti, J. Hirata, J. R. Brown
<p><b>Introduction:</b> Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor that is approved for five indications, including CLL/SLL. Initial results from the SEQUOIA study (NCT03336333), at a median follow-up of 26.2 months, demonstrated superior progression-free survival (PFS) by independent review with zanubrutinib versus bendamustine + rituximab (arms A and B) in patients with treatment-naive CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in patients with del(17p) (arm C). Additionally, the 5-year follow-up in arm A demonstrated durable PFS benefit, with estimated 54- and 60-month PFS rates of 80% and 76%, respectively. Here we report updated results in SEQUOIA arm C, in patients with del(17p), after approximately 5 years of follow-up (data cutoff: Apr 30, 2024).</p><p><b>Methods:</b> Arm C is a nonrandomized cohort of SEQUOIA patients with del(17p) that received zanubrutinib monotherapy. Investigator-assessed PFS, overall survival (OS), ORR, and safety/tolerability were evaluated. Adverse events (AEs) were recorded until disease progression or start of next-line therapy.</p><p><b>Results:</b> Between Feb 2018 and Mar 2019, 111 treatment-naive patients with del(17p) were enrolled to receive zanubrutinib. The median age was 71 years (range, 42–87 years), 79 (71%) were male, 67 (60%) were IGHV unmutated, and 47 (42%) had both del(17p) and <i>TP53</i> mutation. At a median follow-up of 65.8 months (range, 5–75 months), median PFS was not reached. The estimated 60-month PFS rate was 72.2% (62.4%–79.8%) (Figure), or 73.0% (63.3%–80.6%) when adjusted for COVID-19. Median OS was also not reached. The estimated 60-month OS rate was 85.1% (76.9%–90.6%), or 87.0% (79.0%–92.1%) when adjusted for COVID-19. The ORR was 97.3%, and the complete response/complete response with incomplete hematologic recovery rate was 18.2%. Zanubrutinib treatment was ongoing in 62.2% of patients. The most common causes for treatment discontinuation were AEs and progressive disease (in 17.1% and 15.3%, respectively). Key AEs of interest (AEI) included any-grade infection (82%), bleeding (60%), neutropenia (19%), hypertension (18%), anemia (9%), thrombocytopenia (8%), and atrial fibrillation/flutter (7%). Grade ≥ 3 AEI included infection (33%), neutropenia (16%), hypertension (8%), bleeding (6%), atrial fibrillation/flutter (5%), and thrombocytopenia (2%).</p><p><b>Conclusions:</b> With this 5-year follow-up in SEQUOIA, the efficacy of zanubrutinib in treatment-naive higher-risk patients with del(17p) was maintained, and patients continue to demonstrate PFS benefits consistent with the randomized cohort of patients without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated patients with del(17p), suggests that zanubrutinib remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL.</p><p><b
{"title":"SEQUOIA 5-YEAR FOLLOW-UP IN ARM C: FRONTLINE ZANUBRUTINIB IN PATIENTS WITH DEL(17P) AND TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL)","authors":"C. S. Tam, P. Ghia, M. Shadman, T. Munir, S. S. Opat, P. A. Walker, M. Lasica, I. W. Flinn, T. Tian, S. Agresti, J. Hirata, J. R. Brown","doi":"10.1002/hon.70093_72","DOIUrl":"https://doi.org/10.1002/hon.70093_72","url":null,"abstract":"<p><b>Introduction:</b> Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor that is approved for five indications, including CLL/SLL. Initial results from the SEQUOIA study (NCT03336333), at a median follow-up of 26.2 months, demonstrated superior progression-free survival (PFS) by independent review with zanubrutinib versus bendamustine + rituximab (arms A and B) in patients with treatment-naive CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in patients with del(17p) (arm C). Additionally, the 5-year follow-up in arm A demonstrated durable PFS benefit, with estimated 54- and 60-month PFS rates of 80% and 76%, respectively. Here we report updated results in SEQUOIA arm C, in patients with del(17p), after approximately 5 years of follow-up (data cutoff: Apr 30, 2024).</p><p><b>Methods:</b> Arm C is a nonrandomized cohort of SEQUOIA patients with del(17p) that received zanubrutinib monotherapy. Investigator-assessed PFS, overall survival (OS), ORR, and safety/tolerability were evaluated. Adverse events (AEs) were recorded until disease progression or start of next-line therapy.</p><p><b>Results:</b> Between Feb 2018 and Mar 2019, 111 treatment-naive patients with del(17p) were enrolled to receive zanubrutinib. The median age was 71 years (range, 42–87 years), 79 (71%) were male, 67 (60%) were IGHV unmutated, and 47 (42%) had both del(17p) and <i>TP53</i> mutation. At a median follow-up of 65.8 months (range, 5–75 months), median PFS was not reached. The estimated 60-month PFS rate was 72.2% (62.4%–79.8%) (Figure), or 73.0% (63.3%–80.6%) when adjusted for COVID-19. Median OS was also not reached. The estimated 60-month OS rate was 85.1% (76.9%–90.6%), or 87.0% (79.0%–92.1%) when adjusted for COVID-19. The ORR was 97.3%, and the complete response/complete response with incomplete hematologic recovery rate was 18.2%. Zanubrutinib treatment was ongoing in 62.2% of patients. The most common causes for treatment discontinuation were AEs and progressive disease (in 17.1% and 15.3%, respectively). Key AEs of interest (AEI) included any-grade infection (82%), bleeding (60%), neutropenia (19%), hypertension (18%), anemia (9%), thrombocytopenia (8%), and atrial fibrillation/flutter (7%). Grade ≥ 3 AEI included infection (33%), neutropenia (16%), hypertension (8%), bleeding (6%), atrial fibrillation/flutter (5%), and thrombocytopenia (2%).</p><p><b>Conclusions:</b> With this 5-year follow-up in SEQUOIA, the efficacy of zanubrutinib in treatment-naive higher-risk patients with del(17p) was maintained, and patients continue to demonstrate PFS benefits consistent with the randomized cohort of patients without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated patients with del(17p), suggests that zanubrutinib remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL.</p><p><b","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. M. Kahn, J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, A. Herrera
<p>J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, and A. Herrera equally contributing author.</p><p><b>Background</b>: The phase 3 randomized trial S1826 showed that among patients with advanced-stage classic Hodgkin lymphoma (cHL), nivolumab plus doxorubicin, vinblastine, and dacarbazine (N+AVD) resulted in longer progression-free survival (PFS) compared to brentuximab vedotin plus AVD (BV+AVD). We assessed whether the treatment benefits of N+AVD applied to potentially socioeconomically vulnerable populations.</p><p><b>Methods:</b> S1826 was a multicenter trial for patients ≥ 12 years old with stage III or IV newly diagnosed cHL. The trial was stopped early at its pre-specified second interim analysis due to efficacy of the N+AVD arm (hazard ratio [HR] for progression or death, 0.48; 95% confidence interval [CI], 0.27–0.87, <i>p</i> = 0.001). We assessed whether there was any evidence of differential benefit of N+AVD with respect to PFS according to categories of race/ethnicity (Black race and/or Hispanic ethnicity vs. others), rural versus urban residence, area-level socioeconomic deprivation (Area Deprivation Index [ADI] above median, yes vs. no), and insurance status (Medicaid or no insurance vs. others) using interaction tests. Analyses were conducted using Cox regression adjusting for the study-specified stratification variables including age (12 –17 vs. 18–60 vs. > 60 years), the international prognostic score (IPS; 0–3 vs. 4–7), and intent to use radiation (yes vs. no). An overall Type I error rate of alpha = 0.10 was used; multiplicity was accounted for by specifying each individual test at the two-sided alpha = 0.025 level using Bonferroni. If no interaction was found, the marginal association of socioeconomic variables and PFS using multivariable Cox regression was examined.</p><p><b>Results:</b> Of N = 970 eligible patients, 90% were < 60 years, and 56% were male; 11.8% were Black, 12.7% were Hispanic, and 32% had IPS 4–7. Among socioeconomic variables, the combined Black and/or Hispanic patients comprised 24.5%, 13.3% were from rural areas, 50% lived in areas above the median ADI level, and 23.2% had Medicaid or no insurance. In survival analyses, there was no statistically significant evidence that the effect of treatment on PFS differed between levels of the socioeconomic variables (Table). For instance, the PFS HR was 0.52 for Black and/or Hispanic patients and 0.41 for other patients (interaction <i>p</i>-value = 0.60). Across all patients, there was no statistically significant association of Black and/or Hispanic race/ethnicity (HR = 1.10, 95% CI: 0.72–1.69, <i>p</i> = 0.65), rural geography (HR = 1.11, 95% CI: 0.67–1.85, <i>p</i> = 0.67), high ADI (HR = 1.30, 95% CI: 0.89–1.88, <i>p</i> = 0.17), or Medicaid/no insurance (HR = 1.01, 95% CI: 0.63–1.60, <i>p</i> = 0.98) with PFS.</p><p><b>Conclusion:
J. M.昂格，H.李，S. M.卡斯特利诺，H.狄龙，T.埃尔南德斯，S. C.卢瑟福，A.庞尼特，M. LeBlanc， J. Y.宋，S. M.史密斯，A. M.埃文斯，K. M.凯利，J. W.弗里德伯格和A.埃雷拉都是同样贡献的作者。背景：3期随机试验S1826显示，在晚期经典霍奇金淋巴瘤（cHL）患者中，纳武单抗联合阿霉素、长春花碱和达卡巴嗪（N+AVD）比布伦妥昔单抗联合AVD （BV+AVD）可获得更长的无进展生存期（PFS）。我们评估了N+AVD的治疗益处是否适用于潜在的社会经济弱势群体。方法：S1826是一项针对≥12岁的III期或IV期新诊断cHL患者的多中心试验。由于N+AVD组的疗效，该试验在预先指定的第二次中期分析中提前停止(进展或死亡的风险比[HR]为0.48；95%可信区间[CI]， 0.27-0.87, p = 0.001)。根据种族/民族（黑人和/或西班牙裔与其他种族）、农村与城市居住、区域层面的社会经济剥夺（区域剥夺指数高于中位数，是与否）和保险状况（医疗补助或无保险与其他），我们使用相互作用测试评估了是否有任何证据表明N+AVD对PFS有不同的益处。使用Cox回归对研究指定的分层变量进行分析，包括年龄(12 -17岁vs. 18-60岁vs. >；60岁)，国际预后评分(IPS；0-3 vs. 4-7)，以及使用辐射的意图（是vs.否）。总体I型错误率为alpha = 0.10；多重性是通过使用Bonferroni在双侧alpha = 0.025水平上指定每个个体检验来解释的。如果没有发现相互作用，则使用多变量Cox回归检查社会经济变量与PFS的边际关联。结果：在970例符合条件的患者中，90%为<；60岁，男性占56%；11.8%为黑人，12.7%为西班牙裔，32%为IPS 4-7。在社会经济变量中，黑人和/或西班牙裔患者占24.5%，13.3%来自农村地区，50%生活在高于ADI中位数水平的地区，23.2%有医疗补助或没有保险。在生存分析中，没有统计学上显著的证据表明治疗对PFS的影响在不同的社会经济变量水平之间存在差异（表）。例如，黑人和/或西班牙裔患者的PFS HR为0.52，其他患者为0.41（相互作用p值= 0.60）。在所有患者中，黑人和/或西班牙裔人种/民族（HR = 1.10, 95% CI: 0.72-1.69, p = 0.65）、农村地理（HR = 1.11, 95% CI: 0.67 - 1.85, p = 0.67）、高ADI （HR = 1.30, 95% CI: 0.89-1.88, p = 0.17）或医疗补助/无保险（HR = 1.01, 95% CI: 0.63-1.60, p = 0.98）与PFS没有统计学意义的关联。结论：在S1826纳入的晚期cHL患者中，我们没有发现证据表明，与BV+AVD相比，N+AVD的PFS获益会因社会不利因素而显著减弱。这表明N+AVD广泛适用于不同社会经济背景的患者。总体生存分析正在进行中。科研经费声明：美国国立卫生研究院国家癌症研究所U10CA180888、U10CA180819；部分由BMS实现；埃米特,托尼斯蒂芬森白血病淋巴瘤学会（LLS）学者奖；拉里&；丹尼斯·梅森临床学者职业发展奖；V基金会劳埃德家庭临床研究者基金；LLS临床研究学者奖。关键词：癌症健康差异无潜在利益冲突来源
{"title":"THE ASSOCIATION OF SOCIAL DISADVANTAGE WITH OUTCOMES IN PATIENTS WITH ADVANCED-STAGE, CLASSIC HODGKIN LYMPHOMA ENROLLED IN THE PHASE 3 INTERGROUP TRIAL S1826","authors":"J. M. Kahn, J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, A. Herrera","doi":"10.1002/hon.70094_368","DOIUrl":"https://doi.org/10.1002/hon.70094_368","url":null,"abstract":"<p>J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, and A. Herrera equally contributing author.</p><p><b>Background</b>: The phase 3 randomized trial S1826 showed that among patients with advanced-stage classic Hodgkin lymphoma (cHL), nivolumab plus doxorubicin, vinblastine, and dacarbazine (N+AVD) resulted in longer progression-free survival (PFS) compared to brentuximab vedotin plus AVD (BV+AVD). We assessed whether the treatment benefits of N+AVD applied to potentially socioeconomically vulnerable populations.</p><p><b>Methods:</b> S1826 was a multicenter trial for patients ≥ 12 years old with stage III or IV newly diagnosed cHL. The trial was stopped early at its pre-specified second interim analysis due to efficacy of the N+AVD arm (hazard ratio [HR] for progression or death, 0.48; 95% confidence interval [CI], 0.27–0.87, <i>p</i> = 0.001). We assessed whether there was any evidence of differential benefit of N+AVD with respect to PFS according to categories of race/ethnicity (Black race and/or Hispanic ethnicity vs. others), rural versus urban residence, area-level socioeconomic deprivation (Area Deprivation Index [ADI] above median, yes vs. no), and insurance status (Medicaid or no insurance vs. others) using interaction tests. Analyses were conducted using Cox regression adjusting for the study-specified stratification variables including age (12 –17 vs. 18–60 vs. > 60 years), the international prognostic score (IPS; 0–3 vs. 4–7), and intent to use radiation (yes vs. no). An overall Type I error rate of alpha = 0.10 was used; multiplicity was accounted for by specifying each individual test at the two-sided alpha = 0.025 level using Bonferroni. If no interaction was found, the marginal association of socioeconomic variables and PFS using multivariable Cox regression was examined.</p><p><b>Results:</b> Of N = 970 eligible patients, 90% were < 60 years, and 56% were male; 11.8% were Black, 12.7% were Hispanic, and 32% had IPS 4–7. Among socioeconomic variables, the combined Black and/or Hispanic patients comprised 24.5%, 13.3% were from rural areas, 50% lived in areas above the median ADI level, and 23.2% had Medicaid or no insurance. In survival analyses, there was no statistically significant evidence that the effect of treatment on PFS differed between levels of the socioeconomic variables (Table). For instance, the PFS HR was 0.52 for Black and/or Hispanic patients and 0.41 for other patients (interaction <i>p</i>-value = 0.60). Across all patients, there was no statistically significant association of Black and/or Hispanic race/ethnicity (HR = 1.10, 95% CI: 0.72–1.69, <i>p</i> = 0.65), rural geography (HR = 1.11, 95% CI: 0.67–1.85, <i>p</i> = 0.67), high ADI (HR = 1.30, 95% CI: 0.89–1.88, <i>p</i> = 0.17), or Medicaid/no insurance (HR = 1.01, 95% CI: 0.63–1.60, <i>p</i> = 0.98) with PFS.</p><p><b>Conclusion:","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Pettersson, K. Vemuri, M. Berglund, J. Collin, M. Herre, R. Amini, D. Molin, A. Olsson, G. Enblad
<p><b>Introduction:</b> Neutrophil extracellular traps (NETs) are complexes of decondensed chromatin and granule proteins that can be released from activated neutrophils during infections or in inflammatory conditions, including cancer. Accumulation of NETs in tissues and blood can contribute to increased inflammation, thrombosis and organ damage. In several types of solid cancers, NETs have been shown to facilitate metastasis and tumour growth, leading to a worse prognosis. However, little is known about the role of NETs in malignant lymphomas.</p><p><b>Methods:</b> The concentration of NETs was analysed in plasma samples taken at diagnosis from patients with diffuse large B-cell lymphoma (DLBCL, <i>n</i> = 227) and classical Hodgkin lymphoma (cHL, <i>n</i> = 117) in the Uppsala Umeå Comprehensive Cancer Consortium (U-CAN) biobank. Plasma from blood donors (<i>n</i> = 54) were used as healthy controls. NETs were measured using a commercial enzyme-linked immunosorbent assay (ELISA) targeting complexes of citrullinated histones and extracellular DNA, a biomarker with high specificity for NETs. Clinical data, including blood counts at diagnosis and treatment outcome, was extracted from patient records and analysed in relation to the plasma concentrations of NETs.</p><p><b>Results:</b> Higher concentrations of NETs were seen in plasma from DLBCL patients (range 0.62 to 200 ng/ml) compared to cHL patients (<i>p</i> < 0.01, range 0.58 to 62 ng/ml) and healthy controls (<i>p</i> < 0.001, range 1.0 to 37 ng/ml). The level of NETs in cHL was not significantly higher than in control samples. In both DLBCL and cHL, a poorer overall survival was seen in patients with concentrations of NETs above median (7.4 and 5.6 ng/ml respectively, <i>p</i> < 0.05). There was no significant correlation between progression free survival and NETs. In cHL, there was a positive correlation between elevated levels of NETs and age above 45 years (<i>p</i> < 0.05), but no correlation to age was shown in DLBCL. The NET levels did not significantly differ between the sexes. A trend, although not significant, could be seen with increased NET levels in higher stages of both DLBCL and cHL. The plasma concentration of NETs in both lymphoma diseases showed a positive correlation with the neutrophil count in blood (<i>p</i> < 0.05), as well as erythrocyte sedimentation rate (ESR) above 50 mmHg (<i>p</i> < 0.01) at diagnosis.</p><p><b>Conclusions:</b> In line with previous studies on NETs in cancer, we show that high levels of NETs in plasma correlates with worse survival for both DLBCL and cHL patients. However, plasma concentrations were only significantly increased in DLBCL compared to healthy controls, with no correlation to age or sex. Based on the results, NETs could be a possible prognostic marker to further investigate in malignant lymphoma. In both DLBCL and cHL, higher levels of NETs were seen in patients with elevated neutrophil count and high ESR, a sign of
{"title":"INVESTIGATING NEUTROPHIL EXTRACELLULAR TRAPS AS A POSSIBLE PROGNOSTIC MARKER IN DIFFUSE LARGE B-CELL LYMPHOMA AND CLASSICAL HODGKIN LYMPHOMA","authors":"E. Pettersson, K. Vemuri, M. Berglund, J. Collin, M. Herre, R. Amini, D. Molin, A. Olsson, G. Enblad","doi":"10.1002/hon.70094_205","DOIUrl":"https://doi.org/10.1002/hon.70094_205","url":null,"abstract":"<p><b>Introduction:</b> Neutrophil extracellular traps (NETs) are complexes of decondensed chromatin and granule proteins that can be released from activated neutrophils during infections or in inflammatory conditions, including cancer. Accumulation of NETs in tissues and blood can contribute to increased inflammation, thrombosis and organ damage. In several types of solid cancers, NETs have been shown to facilitate metastasis and tumour growth, leading to a worse prognosis. However, little is known about the role of NETs in malignant lymphomas.</p><p><b>Methods:</b> The concentration of NETs was analysed in plasma samples taken at diagnosis from patients with diffuse large B-cell lymphoma (DLBCL, <i>n</i> = 227) and classical Hodgkin lymphoma (cHL, <i>n</i> = 117) in the Uppsala Umeå Comprehensive Cancer Consortium (U-CAN) biobank. Plasma from blood donors (<i>n</i> = 54) were used as healthy controls. NETs were measured using a commercial enzyme-linked immunosorbent assay (ELISA) targeting complexes of citrullinated histones and extracellular DNA, a biomarker with high specificity for NETs. Clinical data, including blood counts at diagnosis and treatment outcome, was extracted from patient records and analysed in relation to the plasma concentrations of NETs.</p><p><b>Results:</b> Higher concentrations of NETs were seen in plasma from DLBCL patients (range 0.62 to 200 ng/ml) compared to cHL patients (<i>p</i> < 0.01, range 0.58 to 62 ng/ml) and healthy controls (<i>p</i> < 0.001, range 1.0 to 37 ng/ml). The level of NETs in cHL was not significantly higher than in control samples. In both DLBCL and cHL, a poorer overall survival was seen in patients with concentrations of NETs above median (7.4 and 5.6 ng/ml respectively, <i>p</i> < 0.05). There was no significant correlation between progression free survival and NETs. In cHL, there was a positive correlation between elevated levels of NETs and age above 45 years (<i>p</i> < 0.05), but no correlation to age was shown in DLBCL. The NET levels did not significantly differ between the sexes. A trend, although not significant, could be seen with increased NET levels in higher stages of both DLBCL and cHL. The plasma concentration of NETs in both lymphoma diseases showed a positive correlation with the neutrophil count in blood (<i>p</i> < 0.05), as well as erythrocyte sedimentation rate (ESR) above 50 mmHg (<i>p</i> < 0.01) at diagnosis.</p><p><b>Conclusions:</b> In line with previous studies on NETs in cancer, we show that high levels of NETs in plasma correlates with worse survival for both DLBCL and cHL patients. However, plasma concentrations were only significantly increased in DLBCL compared to healthy controls, with no correlation to age or sex. Based on the results, NETs could be a possible prognostic marker to further investigate in malignant lymphoma. In both DLBCL and cHL, higher levels of NETs were seen in patients with elevated neutrophil count and high ESR, a sign of","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. D. Dreyfuss, N. Ganesan, B. S. Imber, M. LaRiviere, D. Isrow, J. Plastaras, J. Svoboda, J. Yahalom, C. H. Moskowitz, A. Moskowitz
<p><b>Background:</b> Chemotherapy (chemo) followed by stem cell transplant (SCT) is standard of care for relapsed/refractory (RR) Hodgkin Lymphoma (HL). In a phase II study, we evaluated pembrolizumab (pembro) with involved site radiation therapy (ISRT) as an alternative salvage approach for localized favorable relapse.</p><p><b>Methods:</b> Patients with RR stage IA/IIA, non-bulky (< 10cm) HL after one line of therapy had a PETCT simulation followed by pembro 200 mg IV q 21d for 4 cycles and PETCT simulation 3 wks later. Patients then received ISRT per response as follows: (1) 20 Gy for complete metabolic response (CMR) defined by Deauville Score (DS) 1–3; (2) 30 Gy for partial metabolic response (PMR) or stable disease (SD) (DS 4–5) and negative biopsy; or (3) 36–40 Gy for PMR/SD and positive biopsy. Patients who progressed (PD) were taken off study. PETCT response was documented 4–6 weeks after ISRT. The primary endpoint was CMR rate after pembro-RT. Secondary endpoints were response to single agent pembro, 2-year progression free survival (PFS), and toxicity.</p><p><b>Results:</b> 22 of planned 22 patients enrolled with median age of 36 (range 22–66) and 10 (45%) males. 3 (14%) had stage I, 18 (82%) stage II, and 1 had an unspecified limited stage at initial diagnosis. Frontline therapy was chemotherapy alone in 19 (86%) and combined modality in 3 (14%). 21 (95%) received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), 17 (81%) with < 6 cycles. 14 (64%) had relapsed and 8 (36%) had refractory disease.</p><p>7 (32%) had CMR after pembro, 3 (14%) had PMR/SD with negative biopsy, 6 (27%) had PMR with positive biopsy, 1 (5%) had PMR without biopsy, and 5 (23%) had PD. 17 patients proceeded to ISRT, of whom 7 (41%) with CMR received 20 Gy, 3 (18%) with PMR/SD and negative biopsy received 30 Gy, and 7 (41%) with PMR/SD and positive/no biopsy received 36–40 Gy. Of the 14 with post-RT PET, 12 (86% of these patients, 67% overall) achieved CMR. After median follow up of 34 months (6–79), 2-year PFS was 65% (95% CI: 47–91).</p><p>Five patients progressed on pembro and three relapsed after a median of 12 months (range 7–70) from completion of pembro-RT. Among the patients with PD during or after pembro-RT, three are currently in remission, one is currently undergoing therapy, and the status for the others are unknown. Subsequent treatments included pembro plus gemcitabine/vinorelbine/liposomal doxorubicin followed by ASCT (<i>n</i> = 2), brentuximab vedotin (BV) plus nivolumab followed by ASCT (<i>n</i> = 1) and 2 doses of BV followed by additional RT (<i>n</i> = 1).</p><p>Immune-related toxicities were 3 (14%) grade 1 rash, and 3 (14%) grade 2 hypo/hyperthyroidism. Grade > 2 toxicities were 1 (5%) grade 3 headache, 1 (5%) grade 3 urinary tract infection, 1 (5%) grade 3 encephalopathy, and 1 (5%) grade 4 lipase elevation.</p><p><b>Conclusion:</b> Pembro-RT yielded excellent CMR rates and minimal toxicity. These data suggest pembro-R
{"title":"PEMBROLIZUMAB AND RADIATION THERAPY ALONE AS AN ALTERNATIVE TO TRANSPLANT FOR LOCALIZED FAILURE AFTER CHEMOTHERAPY IN HODGKIN LYMPHOMA: A MULTICENTER PHASE II STUDY","authors":"A. D. Dreyfuss, N. Ganesan, B. S. Imber, M. LaRiviere, D. Isrow, J. Plastaras, J. Svoboda, J. Yahalom, C. H. Moskowitz, A. Moskowitz","doi":"10.1002/hon.70093_129","DOIUrl":"https://doi.org/10.1002/hon.70093_129","url":null,"abstract":"<p><b>Background:</b> Chemotherapy (chemo) followed by stem cell transplant (SCT) is standard of care for relapsed/refractory (RR) Hodgkin Lymphoma (HL). In a phase II study, we evaluated pembrolizumab (pembro) with involved site radiation therapy (ISRT) as an alternative salvage approach for localized favorable relapse.</p><p><b>Methods:</b> Patients with RR stage IA/IIA, non-bulky (< 10cm) HL after one line of therapy had a PETCT simulation followed by pembro 200 mg IV q 21d for 4 cycles and PETCT simulation 3 wks later. Patients then received ISRT per response as follows: (1) 20 Gy for complete metabolic response (CMR) defined by Deauville Score (DS) 1–3; (2) 30 Gy for partial metabolic response (PMR) or stable disease (SD) (DS 4–5) and negative biopsy; or (3) 36–40 Gy for PMR/SD and positive biopsy. Patients who progressed (PD) were taken off study. PETCT response was documented 4–6 weeks after ISRT. The primary endpoint was CMR rate after pembro-RT. Secondary endpoints were response to single agent pembro, 2-year progression free survival (PFS), and toxicity.</p><p><b>Results:</b> 22 of planned 22 patients enrolled with median age of 36 (range 22–66) and 10 (45%) males. 3 (14%) had stage I, 18 (82%) stage II, and 1 had an unspecified limited stage at initial diagnosis. Frontline therapy was chemotherapy alone in 19 (86%) and combined modality in 3 (14%). 21 (95%) received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), 17 (81%) with < 6 cycles. 14 (64%) had relapsed and 8 (36%) had refractory disease.</p><p>7 (32%) had CMR after pembro, 3 (14%) had PMR/SD with negative biopsy, 6 (27%) had PMR with positive biopsy, 1 (5%) had PMR without biopsy, and 5 (23%) had PD. 17 patients proceeded to ISRT, of whom 7 (41%) with CMR received 20 Gy, 3 (18%) with PMR/SD and negative biopsy received 30 Gy, and 7 (41%) with PMR/SD and positive/no biopsy received 36–40 Gy. Of the 14 with post-RT PET, 12 (86% of these patients, 67% overall) achieved CMR. After median follow up of 34 months (6–79), 2-year PFS was 65% (95% CI: 47–91).</p><p>Five patients progressed on pembro and three relapsed after a median of 12 months (range 7–70) from completion of pembro-RT. Among the patients with PD during or after pembro-RT, three are currently in remission, one is currently undergoing therapy, and the status for the others are unknown. Subsequent treatments included pembro plus gemcitabine/vinorelbine/liposomal doxorubicin followed by ASCT (<i>n</i> = 2), brentuximab vedotin (BV) plus nivolumab followed by ASCT (<i>n</i> = 1) and 2 doses of BV followed by additional RT (<i>n</i> = 1).</p><p>Immune-related toxicities were 3 (14%) grade 1 rash, and 3 (14%) grade 2 hypo/hyperthyroidism. Grade > 2 toxicities were 1 (5%) grade 3 headache, 1 (5%) grade 3 urinary tract infection, 1 (5%) grade 3 encephalopathy, and 1 (5%) grade 4 lipase elevation.</p><p><b>Conclusion:</b> Pembro-RT yielded excellent CMR rates and minimal toxicity. These data suggest pembro-R","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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