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Pretransplant desensitization of donor-specific anti-HLA antibodies with plasmapheresis and immunoglobulin produces equivalent outcomes to patients with no donor specific antibodies in haploidentical hematopoietic cell transplant. 在单倍体造血细胞移植中,通过浆细胞和免疫球蛋白对捐献者特异性抗-HLA抗体进行移植前脱敏,与没有捐献者特异性抗体的患者相比,效果相当。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-11 DOI: 10.1080/10428194.2024.2376172
Hunter Cassidy Cochran, Michael Joseph Slade, Chang Liu, Feng Gao, Sonia Godbole, Aaron Pruitt, Elisa De Togni, Brenda Grossman, Ramzi Abboud

Haploidentical hematopoietic cell transplants (haplo-HCT) with donor-specific anti-HLA antibodies (DSAs) are associated with high rates of primary graft failure and poor overall survival (OS). Limited data exists regarding the effect of desensitization. Our institution began routine desensitization for patients with DSAs in 2014. Adult patients undergoing haplo-HCT at Washington University from 2009-2021 were identified and divided into three cohorts: no DSA, untreated DSA (2009-2014) or treated DSA (2014-2021). Desensitization therapy using plasmapheresis and IVIg was performed. Retrospectively, 304 patients were identified. 14 of 30 patients with DSAs underwent desensitization. By day +2, 57% of patients cleared all DSAs. After multivariable analysis, OS was similar between treated DSA and no DSA (HR: 0.69, p = 0.37). Untreated DSA had significantly lower OS compared to no DSA group (HR 1.80, p = 0.046). Desensitization with a backbone of plasmapheresis and IVIg before haplo-HCT may produce similar outcomes to patients without DSAs.

存在供体特异性抗-HLA抗体(DSAs)的单倍体造血细胞移植(haplo-HCT)与初次移植失败率高和总存活率(OS)低有关。有关脱敏效果的数据十分有限。我院于 2014 年开始对 DSA 患者进行常规脱敏治疗。我们对 2009-2021 年期间在华盛顿大学接受单倍体-HCT 的成人患者进行了鉴定,并将其分为三个队列:无 DSA、未治疗的 DSA(2009-2014 年)或治疗的 DSA(2014-2021 年)。使用血浆置换术和IVIg进行脱敏治疗。回顾性研究共发现了 304 名患者。30名DSA患者中有14名接受了脱敏治疗。到第 +2 天,57% 的患者清除了所有 DSA。经过多变量分析,接受治疗的 DSA 与未接受治疗的 DSA 的 OS 相似(HR:0.69,P = 0.37)。与无DSA组相比,未经治疗的DSA的OS明显较低(HR 1.80,P = 0.046)。在单倍体肝细胞移植前以浆细胞吸出术和IVIg为骨干进行脱敏治疗可能会产生与无DSA患者相似的结果。
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引用次数: 0
CRLF2 and IKZF1 abnormalities in childhood hematological malignancies other than B-cell Acute Lymphoblastic Leukemia. 儿童血液恶性肿瘤(B 细胞急性淋巴细胞白血病除外)中的 CRLF2 和 IKZF1 异常。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-21 DOI: 10.1080/10428194.2024.2378817
Dafné Moreno-Lorenzana, Rocío Juárez-Velázquez, Adriana Reyes-León, Daniel Martínez-Anaya, Luis Juárez-Villegas, Martha Zapata Tarrés, Norma López Santiago, Patricia Pérez-Vera

Rearrangements and overexpression of CRLF2 are hallmarks of poor outcomes in BCR::ABL1-like B-ALL, and CRLF2 overexpression is a high-risk marker in T-ALL. However, CRLF2 alterations in pediatric hematologic malignancies other than B-ALL have not been reported. In this study, we analyzed the CRLF2 overexpression, rearrangements (P2RY8::CRLF2 and IGH::CRLF2), activation (pSTAT5 and pERK), and the expression of dominant-negative IKZF1 isoforms (Ik6 and Ik8), implied in CRLF2 dysregulation, in 16 pediatric patients (AML, n = 9; T-ALL, n = 3; LBL, n = 2; HL, n = 1; cytopenia, n = 1). A high frequency of CRLF2 rearrangements and overexpression was found in the 16 patients: 28.6% (4/14) showed CRLF2 overexpression, 93.8% (15/16) were positive for CRLF2 total protein (cell-surface and/or cytoplasmic), while 62.5% (10/16) were positive for P2RY8::CRLF2 and 12.6% (2/16) for IGH::CRLF2. In addition, 43.8% (7/16) expressed Ik6 and Ik8 isoforms. However, only a few patients were positive for the surrogate markers pSTAT5 (14.3%; 2/14) and pERK (21.4%; 3/14).

CRLF2的重排和过表达是BCR::ABL1样B-ALL不良预后的标志,而CRLF2的过表达是T-ALL的高危标志。然而,除 B-ALL 外,CRLF2 在小儿血液恶性肿瘤中的改变尚未见报道。在本研究中,我们分析了CRLF2的过表达、重排(P2RY8::CRLF2和IGH::CRLF2)、激活(pSTAT5 和 pERK)以及显性阴性 IKZF1 同工酶(Ik6 和 Ik8)的表达,这意味着 16 名儿科患者(AML,n = 9;T-ALL,n = 3;LBL,n = 2;HL,n = 1;全血细胞减少症,n = 1)中 CRLF2 的失调。在这16名患者中,CRLF2重排和过表达的频率很高:28.6%(4/14)的患者表现为CRLF2过表达,93.8%(15/16)的患者CRLF2总蛋白(细胞表面和/或胞质)阳性,62.5%(10/16)的患者P2RY8::CRLF2阳性,12.6%(2/16)的患者IGH::CRLF2阳性。此外,43.8%(7/16)的患者表达 Ik6 和 Ik8 同工酶。然而,只有少数患者的替代标记物 pSTAT5(14.3%;2/14)和 pERK(21.4%;3/14)呈阳性。
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引用次数: 0
Clinicopathologic characteristics of de novo NF1-mutated acute myeloid leukemia. 新发 NF1 基因突变急性髓性白血病的临床病理特征。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-27 DOI: 10.1080/10428194.2024.2382329
Bo Zhang, Sameh Mahsoub, Olga Weinberg, Sharon Koorse Germans
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引用次数: 0
A case report of solitary presentations of large B-cell lymphoma of immune-privileged sites (IP-LBCL) in the testis, vitreous body, and skin. 睾丸、玻璃体和皮肤单发免疫优势部位大B细胞淋巴瘤(IP-LBCL)病例报告。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-30 DOI: 10.1080/10428194.2024.2385495
Jeffrey Ahn, Yi Ouyang, Graham Velasco, Ann Eapen, Helen Ma
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引用次数: 0
A phase I trial of vaccination with lethally irradiated lymphoma cells admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells for the treatment of follicular lymphoma. 用经致死性照射的淋巴瘤细胞与分泌粒细胞-巨噬细胞集落刺激因子的 K562 细胞混合接种治疗滤泡性淋巴瘤的 I 期试验。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-21 DOI: 10.1080/10428194.2024.2381651
Eric Jacobsen, Ashley Plant, Robert Redd, Philippe Armand, Mikaela McDonough, Udochukwu Ihuoma, David C Fisher, Ann LaCasce, Jerome Ritz, Glenn Dranoff, Arnold Freedman

Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.

目前已对几种治疗滤泡性淋巴瘤的疫苗策略进行了测试,但没有一种策略被证明是成功的。在I期剂量递增方案中,我们开发了一种疫苗,由经致死性照射的全淋巴瘤细胞与K562细胞混合而成,K562细胞能分泌粒细胞-巨噬细胞集落刺激因子(GM-K562)(ClinicalTrials.gov identifier:NCT00487305)。1、2或3级A型滤泡性淋巴瘤患者根据之前的治疗情况分为2个研究级别,最多可接种6种疫苗。疫苗含有5×106或1×107 GM-K562细胞与自体肿瘤细胞混合的剂量水平,剂量从1×105到5×107不等。根据迟发型超敏反应、B细胞和T细胞亚群以及自然杀伤细胞亚群的评估,相关研究并未显示出明显的免疫反应。未来的疫苗研究应侧重于识别淋巴瘤特异性免疫原蛋白和改进疫苗免疫佐剂。
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引用次数: 0
Homoharringtonine sensitized resistant acute myeloid leukemia cells to venetoclax-induced apoptosis. 荷包牡丹碱能使耐药急性髓性白血病细胞对 Venetoclax 诱导的细胞凋亡敏感。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-05 DOI: 10.1080/10428194.2024.2400228
Zhao Yin, Ya Gao, Xiaoyin Bu, Junhui Wang, Zurong Yao, Qifa Liu, Yu Zhang, Guopan Yu, Baohong Ping

Venetoclax (VEN), a B-cell lymphoma 2 (BCL-2) selective inhibitor, is widely used for treating acute myeloid leukemia (AML) with promising results. However, the anti-leukemic effect of VEN in relapsed/refractory (R/R)- AML requires improvement. In this study, we observed that combining homoharringtonine (HHT) with VEN plus azacitidine resulted in a significantly higher response and better survival than VA alone in patients with R/R-AML. Basic research indicates that HHT combined with VEN has a highly synergistic effect against both resistant AML cells and primary cells with/without mesenchymal stem cell (MSC) co-culture in vivo, inhibiting proliferation and colony-forming capacity of AML cells associated with concomitant cell cycle arrest. Mechanistically, HHT sensitizes AML cells to VEN by downregulating the anti-apoptotic proteins MCL-1/BCL-xL, activating reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and attenuating fatty acid (FA) uptake. These findings adding HHT to VEN-based regimens may enhance outcomes in R/R-AML patients.

Venetoclax(VEN)是一种B细胞淋巴瘤2(BCL-2)选择性抑制剂,被广泛用于治疗急性髓性白血病(AML),并取得了良好的疗效。然而,VEN在复发/难治性(R/R)AML中的抗白血病效果有待改善。在这项研究中,我们观察到,在复发性/难治性急性髓细胞白血病(R/R-AML)患者中,将同型半胱氨酸(HHT)与 VEN 加上阿扎胞苷联合使用,比单独使用 VA 的反应明显更强,生存率更高。基础研究表明,HHT 联合 VEN 对体内耐药急性髓细胞白血病细胞和间充质干细胞(MSC)共培养/不共培养的原代细胞均有高度协同作用,可抑制急性髓细胞白血病细胞的增殖和集落形成能力,同时抑制细胞周期停滞。从机理上讲,HHT通过下调抗凋亡蛋白MCL-1/BCL-xL、激活活性氧(ROS)导致线粒体膜电位丧失和减少脂肪酸(FA)摄取,使AML细胞对VEN敏感。这些研究结果表明,在基于 VEN 的治疗方案中加入 HHT 可提高 R/R-AML 患者的治疗效果。
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引用次数: 0
IKZF1 in acute lymphoblastic leukemia: the rise before the fall? 急性淋巴细胞白血病中的 IKZF1:先兴后衰?
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-08-29 DOI: 10.1080/10428194.2024.2396046
Anna Østergaard, Judith M Boer, Frank N van Leeuwen, Rob Pieters, Monique L Den Boer

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents and in recent decades, the survival rates have risen to >90% in children largely due the introduction of risk adapted therapy. Therefore, knowledge of factors influencing risk of relapse is important. The transcription factor IKAROS is a regulator of lymphocyte development and alterations of its coding gene, IKZF1, are frequent in ALL and are associated with higher relapse risk. This concise review will discuss the normal function of IKAROS together with the effect of gene alterations in ALL such as relieved energy restriction and altered response to anti-leukemic drugs. Besides the biology, the clinical impact of gene alterations in the different subtypes of ALL will be discussed. Finally, possibilities for treating ALL with IKZF1 alterations will be considered including novel therapies like cell signaling inhibitors and immunotherapy.

急性淋巴细胞白血病(ALL)是儿童和青少年中最常见的恶性肿瘤,近几十年来,儿童的存活率已上升到90%以上,这主要归功于风险适应疗法的引入。因此,了解影响复发风险的因素非常重要。转录因子IKAROS是淋巴细胞发育的调节因子,其编码基因IKZF1的改变在ALL中很常见,并与较高的复发风险相关。这篇简明综述将讨论 IKAROS 的正常功能,以及基因改变对 ALL 的影响,如能量限制的缓解和对抗白血病药物反应的改变。除了生物学方面,还将讨论基因改变对不同亚型 ALL 的临床影响。最后,还将探讨治疗IKZF1基因改变的ALL的可能性,包括细胞信号抑制剂和免疫疗法等新型疗法。
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引用次数: 0
Correction. 校正
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2023-10-05 DOI: 10.1080/10428194.2023.2255364
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引用次数: 0
Anti-thymocyte globulin combined with post-transplantation cyclophosphamide reduce graft-versus-host disease in hematopoietic stem cell transplantation for pediatric leukemia. 抗胸腺细胞球蛋白与移植后环磷酰胺联合使用可减少小儿白血病造血干细胞移植中的移植物抗宿主疾病。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-07 DOI: 10.1080/10428194.2024.2376179
Mengze Hu, Junhui Li, Tao Hu, Zhaoxia Zhang, Shunqiao Feng, Litian Xuan, Rong Liu

This retrospective analysis evaluated the use of anti-thymocyte globulin (ATG) with or without post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis in children with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT). The study included 57 children, with 35 in the ATG-PTCy group and 22 in the ATG group. While overall incidence of acute and chronic GvHD did not differ significantly between groups, the ATG-PTCy group had lower rates of grade II-IV acute GvHD (p = 0.013) and moderate-to-severe chronic GvHD (p = 0.001) compared to the ATG group. Importantly, ATG-PTCy significantly improved GvHD/relapse-free survival (GRFS) compared to ATG (65.71% vs. 36.63%; p = 0.003). There were no differences in engraftment, infection rates, immune reconstitution, overall survival, leukemia-free survival, relapse rate, or non-relapse mortality between the two groups. Combining ATG with PTCy may reduce moderate-to-severe GvHD and improve GRFS in children undergoing HSCT for acute leukemia.

这项回顾性分析评估了在接受造血干细胞移植(HSCT)的急性白血病患儿中使用抗胸腺细胞球蛋白(ATG)联合或不联合移植后环磷酰胺(PTCy)预防移植物抗宿主病(GvHD)的情况。这项研究包括57名儿童,其中ATG-PTCy组35人,ATG组22人。虽然急性和慢性并发症的总体发生率在各组间无显著差异,但与ATG组相比,ATG-PTCy组的II-IV级急性并发症(p = 0.013)和中度至重度慢性并发症(p = 0.001)发生率较低。重要的是,与ATG组相比,ATG-PTCy能显著提高抗排异/无复发生存率(GRFS)(65.71% vs. 36.63%; p = 0.003)。两组在移植、感染率、免疫重建、总生存期、无白血病生存期、复发率或非复发死亡率方面没有差异。在接受造血干细胞移植治疗急性白血病的儿童中,ATG与PTCy联合治疗可减少中度至重度GvHD,提高GRFS。
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引用次数: 0
A case of testicular diffuse large B-cell lymphoma with late relapse in the skin: the critical role of comparative phenotypic, clonality, and cytogenetic testing. 一例皮肤晚期复发的睾丸弥漫大 B 细胞淋巴瘤:比较表型、克隆和细胞遗传学检测的关键作用。
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-17 DOI: 10.1080/10428194.2024.2374455
Oluwaseyi Adeuyan, Madhu M Ouseph, Liming Bao, Michael J Kluk, Jonathan S Goldberg, Larisa J Geskin, Cynthia M Magro
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引用次数: 0
期刊
Leukemia & Lymphoma
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