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Co-transfection of murine NXPE2 and murine glycophorin A confers reactivity with Ter-119. 共同转染小鼠 NXPE2 和小鼠糖蛋白 A 可与 Ter-119 发生反应。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285168
Gregory R Keele, Ariel M Hay, Nadia K Holness, Arijita Jash, Sarah E Ewald, Callan O'Connor, Matthew Vincent, Monika Dzieciatkowska, Angelo D'Alessandro, Gary A Churchill, James C Zimring
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引用次数: 0
FLT3 inhibitors potentially improve response rates in acute myeloid leukemia harboring t(6;9)(DEK::NUP214): the Mayo Clinic experience. FLT3抑制剂可提高携带t(6;9)(DEK::NUP214)的急性髓性白血病患者的应答率:梅奥诊所的经验。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285359
Clifford M Csizmar, Antoine N Saliba, Patricia T Greipp, Hassan Alkhateeb, Kebede H Begna, James M Foran, Naseema Gangat, William J Hogan, C Christopher Hook, Mark R Litzow, Abhishek A Mangaonkar, Jeanne M Palmer, Animesh Pardanani, Mithun V Shah, Ayalew Tefferi, Mehrdad Hefazi Torghabeh, Alexandra P Wolanskyj-Spinner, Mrinal M Patnaik, Scott H Kaufmann, Aref Al-Kali
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引用次数: 0
A targeted gene signature stratifying mediastinal gray zone lymphoma into classical Hodgkin lymphoma-like or primary mediastinal B-cell lymphoma-like subtypes. 将纵隔灰区淋巴瘤分为经典HL样或PMBL样亚型的靶向基因特征。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285266
Grazia Gargano, Maria Carmela Vegliante, Flavia Esposito, Susanna A Pappagallo, Elena Sabattini, Claudio Agostinelli, Stefano A Pileri, Valentina Tabanelli, Maurilio Ponzoni, Luisa Lorenzi, Fabio Facchetti, Arianna Di Napoli, Marco Lucioni, Marco Paulli, Lorenzo Leoncini, Stefano Lazzi, Stefano Ascani, Giuseppina Opinto, Gian Maria Zaccaria, Giacomo Volpe, Paolo Mondelli, Antonella Bucci, Laura Selicato, Antonio Negri, Giacomo Loseto, Felice Clemente, Anna Scattone, Alfredo F Zito, Luca Nassi, Nicoletta Del Buono, Attilio Guarini, Sabino Ciavarella
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引用次数: 0
Management of complications of chimeric antigen receptor T-cell therapy: a report by the European Society of Blood and Marrow Transplantation. 嵌合抗原受体 T 细胞疗法并发症的处理:欧洲血液和骨髓移植学会报告。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2023.284810
Olaf Penack, Christophe Peczynski, William Boreland, Daniel Wolff, Ivan Moiseev, Hélène Schoemans, Christian Koenecke, Charlotte Graham, Zinaida Peric

Chimeric antigen receptor (CAR) T cells are in standard clinical use to treat relapsed or refractory hematologic malignancies, such as non-Hodgkin lymphoma, multiple myeloma and acute lymphoblastic leukemia. Owing to the rapidly progressing field of CAR T-cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between European centers in prevention, diagnosis and management of short- and long-term complications. To capture the current CAR T-cell management among European Society for Blood and Marrow Transplantation (EBMT) centers and to determine the medical need and specific areas for future clinical research the EBMT Transplant Complications Working Party performed a survey among 227 EBMT CAR T-cell centers. We received complete servey answers from 106 centers (47%) addressing questions in the areas of product selection, CAR T-cell logistics, management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome as well as management in later phases including prolonged cytopenias. We identified common patterns in complication management, but also significant variety in clinical management of the centers in important aspects. Our results demonstrate a high medical need for treatment harmonization and future clinical research in the following areas: treatment of steroid-refractory and very severe cytokine release syndrome/neurotoxicity, treatment of cytopenia, early discharge and outpatient management, as well as immunoglobulin substitution.

CAR-T 细胞是治疗复发或难治性血液系统恶性肿瘤(如非霍奇金淋巴瘤、多发性骨髓瘤和急性淋巴细胞白血病)的标准临床疗法。由于CAR-T细胞疗法进展迅速,且缺乏公认的治疗指南,我们假设欧洲各中心在短期和长期并发症的预防、诊断和管理方面存在显著差异。为了了解 EBMT 中心目前的 CAR-T 细胞管理情况,确定医疗需求和未来临床研究的具体领域,EBMT 移植并发症工作组对 227 个 EBMT CAR-T 细胞中心进行了调查。我们从 106 个中心(47%)收到了完整的调查问卷,涉及产品选择、CAR-T 细胞物流、细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的管理以及包括长期细胞减少症在内的后期管理等方面的问题。我们发现了并发症管理的共同模式,但各中心的临床管理在重要方面也存在很大差异。我们的研究结果表明,医学界非常需要在以下方面协调治疗和开展未来的临床研究:类固醇难治性和非常严重的 CRS/神经毒性的治疗、细胞减少症的治疗、早期出院和门诊管理以及免疫球蛋白替代。
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引用次数: 0
Clonal evolution from B-cell acute lymphoblastic leukemia with BCR::ABL1 multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy. 多次抗 CD19 嵌合抗原受体 T 细胞治疗后,从 BCR::ABL1 多系受累的 B 细胞急性淋巴细胞白血病到急性髓细胞白血病的克隆演变。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285574
Mei-Jing Liu, Lan Dai, Li Yao, Kai-Wen Tan, Han-Yu Cao, Si-Man Huang, Chao-Ling Wan, Yuan-Hong Huang, Yang Zhang, Wen-Jie Gong, Sheng-Li Xue
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引用次数: 0
Outcomes and genetic dynamics of acute myeloid leukemia at first relapse. 急性髓性白血病首次复发的结果和遗传动态。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285057
Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D DiNardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended to disappear, whereas clonal hematopoiesis-related mutations or TP53 tended to persist. Patients with normal karyotypes tended to acquire cytogenetic abnormalities at relapse. Patients treated intensively had a higher rate of emergence of TP53 mutations (16%), compared to patients given low-intensity treatment (1%, P=0.009). The overall response rates were 38% and 35% for patients treated with salvage intensive treatment or low-intensity treatment, respectively. Seventeen patients (10%) underwent allogeneic stem cell transplantation after salvage therapy. The median overall survival duration after relapse was 5.3 months, with a 1-year overall survival rate of 17.6%. Complex karyotype (hazard ratio [HR]=2.14, P<0.001), a KMT2A rearrangement (HR=3.52, P=0.011), time in remission <12 months (HR=1.71, P=0.011), and an elevated white blood cell count at relapse (HR=2.38, P=0.005) were independent risk factors for overall survival duration. More effective frontline and maintenance therapies are warranted to prevent relapsed AML.

复发急性髓性白血病(rAML)患者的预后令人沮丧。我们对复发性急性髓细胞白血病患者进行了全面分析,以确定遗传动态和生存预测因素。我们分析了 875 名接受强化治疗(IT)或低强度治疗(LIT)的新诊断急性髓细胞白血病患者。在这些患者中,197人随后出现了rAML。我们获得了 164 名患者的数据,其中从 CR/CRi 到复发的中位时间为 6.5 个月。164名患者中有35名(21%)在异基因造血干细胞移植(alloSCT)后复发。复发时,参与通路信号转导的基因突变往往消失,而克隆造血相关突变或TP53往往持续存在。核型正常的患者在复发时往往会出现细胞遗传学异常。与接受LIT治疗的患者(1%,P = 0.009)相比,接受IT治疗的患者出现TP53突变的比例更高(16%)。接受抢救性 IT 或 LIT 治疗的患者的总体反应率分别为 38% 和 35%。17名患者(10%)在抢救治疗后接受了异体干细胞移植。复发后的中位总生存期(OS)为5.3个月,1年OS率为17.6%。复杂核型(危险比 [HR] = 2.14,P < 0.001)、KMT2A重排(HR = 3.52,P = 0.011)、缓解时间<12个月(HR = 1.71,P = 0.011)和复发时白细胞计数升高(HR = 2.38,P = 0.005)是影响OS持续时间的独立危险因素。需要更有效的前线和维持疗法来预防rAML。
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引用次数: 0
Prognostic impact of 'multi-hit' versus 'single-hit' TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases. 急性髓性白血病患者中 "多击 "与 "单击 "TP53 改变的预后影响:髓系恶性肿瘤和肿瘤性疾病联盟的研究结果。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285000
Talha Badar, Ahmad Nanaa, Ehab Atallah, Rory M Shallis, Emily C Craver, Zhuo Li, Aaron D Goldberg, Antoine N Saliba, Anand Patel, Jan P Bewersdorf, Adam Duvall, Madelyn Burkart, Danielle Bradshaw, Yasmin Abaza, Maximilian Stahl, Neil Palmisiano, Guru Subramanian Guru Murthy, Amer M Zeidan, Vamsi Kota, Mrinal M Patnaik, Mark R Litzow

While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation (TP53MT) compared to a single-hit (SH) mutation in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an in-depth analysis utilizing data from ten US academic institutions to study differences in molecular characteristics and outcomes of SH (N=139) versus MH (N=243) TP53MT AML. Complex cytogenetics were more common in MH than in SH TP53MT AML (P<0.001); whereas ASXL1 (P<0.001), RAS (P<0.001), splicing factor (P=0.003), IDH1/2 (P=0.001), FLT3 ITD (P<0.001) and NPM1 (P=0.005) mutations clustered significantly with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between patients with SH or MH disease (event-free survival: 3.0 vs. 2.20 months, respectively, P=0.22; overall survival: 8.50 vs. 7.53 months, respectively, P=0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation as a time-dependent covariate were associated with superior event-free survival (hazard ratio [HR]=0.44, 95% confidence interval [95% CI]: 0.19-1.01, P=0.05 and HR=0.34, 95% CI: 0.18-0.62, P<0.001) and overall survival (HR=0.24, 95% CI: 0.08-0.71, P=0.01 and HR=0.28, 95% CI: 0.16-0.47, P<0.001). Complex cytogenetics (HR=1.56, 95% CI: 1.01-2.40, P=0.04) retained an unfavorable significance for overall survival. Our analysis suggests that MH TP53MT is less relevant in independently predicting outcomes in patients with AML than in those with MDS.

虽然有明确的证据表明,在低风险骨髓增生异常综合征(MDS)中,多基因突变(MH)TP53 与单基因突变(SH)相比预后较差,但在高风险 MDS 和急性髓性白血病(AML)中的数据却相互矛盾。我们利用 10 家美国学术机构的数据进行了深入分析,研究了 SH(n= 139)与 MH(n= 243)TP53MTAML 的分子特征和预后差异。与 SH TP53MT AML 相比,复杂细胞遗传学(CG)在 MH 中更为常见(p
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引用次数: 0
Multiple myeloma in the young: insights on prognosis, clinical features and treatment outcome derived from nationwide German registry data and a nested multicenter sample. 年轻人中的多发性骨髓瘤:从德国全国登记数据和巢式多中心样本中得出的有关预后、临床特征和治疗效果的见解。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285630
Abdulaziz Kamili, Paymon Ahmadi, Lisa Leypoldt, Franziska Marquard, Christoph Schaefers, Ricardo Kosch, Frederik Peters, Henrik Kusche, Tanja Zamrik, Christine Hanoun, Maximilian Seib, Evgenii Shumilov, Theo Leitner, Cyrus Khandanpour, Carsten Bokemeyer, Katja Weisel, Susanne Ghandili
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引用次数: 0
Nodular lymphocyte-predominant Hodgkin lymphoma: advances in disease biology, risk stratification, and treatment. 结节性淋巴细胞为主的霍奇金淋巴瘤:疾病生物学、风险分层和治疗方面的进展。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2024.285903
Ross T Salvaris, Benjamin M Allanson, Graham Collins, Chan Cheah

Recent updates have detailed how patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) may be better risk stratified using prognostic scoring systems. Most patients with NLPHL present with early-stage disease and have an indolent disease course. To reflect these differences from classic Hodgkin lymphoma, nomenclature has been updated to recognize nodular lymphocyte-predominant B-cell lymphoma as an alternative to NLPHL. The Global NLPHL One Working Group have published their pivotal dataset in 2024 which challenges the prognostic significance of variant immunoarchitectural (IAP) patterns and proposes a new prognostic scoring system. Key identified prognostic factors include age >45 years, stage III-IV disease, hemoglobin <10.5 g/dL and splenic involvement. After multivariate analysis, variant IAP was not shown to be associated with inferior outcome. As most patients with NLPHL have excellent long-term survival, identifying patients where treatment de-escalation is appropriate will help to minimize toxicity. De-escalation strategies include observation after fully resected stage I disease, active surveillance, anti-CD20 antibody monotherapy, radiotherapy in early-stage disease, and avoiding anthracycline- or bleomycin-containing chemotherapy regimens. Evidence supporting the use of novel therapies remains limited with disappointing results from a recently published study of ibrutinib in patients with relapsed NLPHL. Hopefully, future trials will investigate novel agents such as checkpoint inhibitors, T-cell engaging antibodies and chimeric antigen receptor T-cell therapy.

最近的更新详细介绍了如何利用预后评分系统更好地对结节性淋巴细胞占优势的霍奇金淋巴瘤(NLPHL)患者进行风险分层。大多数 NLPHL 患者都是早期发病,病程缓慢。为了反映这些与典型霍奇金淋巴瘤的不同之处,对术语进行了更新,将结节性淋巴细胞占优势的B细胞淋巴瘤作为NLPHL的替代。全球NLPHL工作组于2024年公布了他们的关键数据集,该数据集对变异免疫结构(IAP)模式的预后意义提出了质疑,并提出了新的预后评分系统。已确定的主要预后因素包括年龄大于 45 岁、III-IV 期疾病、血红蛋白。
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引用次数: 0
Late-onset NPM1 mutation in a MYC-amplified relapsed/refractory acute myeloid leukemia patient treated with gemtuzumab ozogamicin and glasdegib. 一名接受吉妥珠单抗奥佐米星和格拉斯替吉治疗的 MYC 扩增复发/难治性急性髓性白血病患者的晚期 NPM1 突变。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 DOI: 10.3324/haematol.2023.284922
Sonia Jaramillo, Michael Scherer, Chelsea Szu-Tu, Sergi Beneyto-Calabuig, Carsten Müller-Tidow, Richard F Schlenk, Michael Hundemer, Lars Velten, Caroline Pabst
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引用次数: 0
期刊
Haematologica
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