Volume 07 · Issue 03 · 2025

Infections are frequent complications in patients with hematological disorders, and pathogen diagnosis remains challenging. Metagenomic next-generation sequencing (mNGS) is an unbiased high-throughput technology that has been widely applied in the diagnosis of infectious diseases. However, to date, there are no established international guidelines or expert consensuses regarding the use of mNGS to diagnose infections in patients with hematologic disorders. The Anti-Infection Study Group of the Chinese Society of Hematology invited experts in the fields of hematology, microbiology, and mNGS technology to draft an expert consensus focused on clinical indications, sample collection, quality control, and interpretation of results. This consensus will likely contribute to clarifying the medical indications for mNGS testing, optimizing the interpretation of reports, and becoming an inspiration for global practice.

Chimeric antigen receptor (CAR) T-cell therapy is an epoch-making immunotherapy for the treatment of relapsed or refractory (r/r) blood tumors, as demonstrated by its successful implementation in r/r B cell-derived malignancies. However, replicating this success in T-cell leukemia or lymphoma remains challenging. Among the various potential target antigens, CD7 has garnered attention as a promising candidate. CD7 CAR-T therapy is one of the most extensively studied approaches for treating r/r T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) and r/r acute myeloid leukemia (AML). Based on the source of T cells, CAR-T products can be categorized as autologous and allogeneic, both of which are being tested in clinical trials, each offering specific advantages. Allogeneic CD7 CAR-T cells outperform autologous cells in terms of reducing manufacturing costs, ensuring consistent quality, and improving affordability and availability. Despite these advantages, challenges like graft-versus-host disease (GVHD), host-versus-graft reaction (HVGR), and fratricide pose significant barriers to the clinical application of allogeneic CD7 CAR-T cells. However, innovative gene-editing techniques, such as CRISPR/Cas9 and base editing, and more promising cell sources, such as natural killer T (NKT) cells and induced pluripotent stem cells (iPSCs), are emerging as potential solutions. In this review, we discuss the different categories of CD7 CAR-T products, their application in clinical settings, and directions for refinement.

To investigate the efficacy and prognosis of umbilical cord blood transplantation (UCBT) in patients with acute leukemia (AL) and a history of central nervous system leukemia (CNSL). We retrospectively evaluated 62 patients with AL and a history of CNSL who underwent UCBT at our center between January 2015 and December 2022 (CNSL-positive group). From a concurrent cohort (n = 777) without a history of CNSL, propensity score matching at a 1:2 ratio was conducted based on age, sex, and diagnosis to select 124 matched controls (CNSL-negative group). The results revealed a significantly higher 4-year cumulative incidence of relapse (28.8% vs 16.8%, p = 0.038) and central nervous system (CNS) relapse after UCBT (14.7% vs 3.7%, p = 0.004) in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival (42.0% vs 66.2%, p = 0.004) and overall survival (49.6% vs 69.9%, p = 0.009) rates in the CNSL-positive group were significantly lower than those in the CNSL-negative group. Fine-Gray proportional hazard regression multivariate analysis identified pretransplant CNSL history as an independent high-risk factor for CNS relapse after UCBT (hazard ratio [HR] = 5.710, 95% confidence interval [CI] = 1.737-18.770, p = 0.004). These findings underscore the need to optimize conditioning regimens and graft-vs-host disease prophylaxis and explore novel prophylactic strategies for UCBT to improve long-term survival in patients with AL and a history of CNS involvement.

Due to the limited availability of effective treatment therapies, patients with refractory and relapsed acute myeloid leukemia (AML) often have poor prognoses. Therefore, identifying new therapeutic targets to improve the treatment landscape and enhance AML outcomes is critical. In this study, we demonstrated for the first time that alpha-enolase (ENO1) is markedly overexpressed in AML and is closely associated with poor prognosis. In vitro experiments revealed that ENO1 knockdown (shENO1) significantly inhibited cell proliferation and invasion, and concomitantly induced cell cycle arrest. In vivo, a mouse model engrafted with U937-shENO1 cells exhibited markedly prolonged overall survival compared with a model implanted with U937 cells. Mechanistically, ENO1 operates by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, as evidenced by the reversal of shENO1 function through ERK activation. Collectively, our findings highlight ENO1 as a promising therapeutic target in AML.

致编辑：

关于脐带血（UCB）冷冻保存损伤的综合研究结果，可以通过用萝卜硫素（SF）恢复线粒体功能来缓解，萝卜硫素是一种能够消除线粒体活性氧（ROS）过量产生的抗氧化剂，最近发表在临床研究杂志由黄耀进担任首席科学家，陶成担任高级研究员，来自天津健康科学研究所（北京协和医学院）的团队。¹

大多数患有特发性血小板减少性紫癜（ITP）的儿童对初始治疗有反应，但有些没有反应，有些反应者复发。如何治疗这些孩子是有争议的。建议的干预措施包括IGIV、抗CD20抗体（如利妥昔单抗）、免疫抑制药物、脾切除术、血小板生成素受体激动剂（如艾曲泊帕、romiplostim和hetrombopag），甚至脐带血细胞衍生的间充质基质细胞输注。^1,2,3,4,5,6这些干预措施对一些儿童有效，但复发很常见。

大颗粒淋巴细胞白血病(LGLL)是一种相对罕见的血液系统恶性肿瘤，其特征在于细胞毒性淋巴细胞的克隆性扩增，特别是CD8+T细胞(T-LGLL)，并且在某些情况下，自然杀伤(NK)细胞(NK-LGLL)。¹虽然罕见，但LGLL具有临床意义，约占所有慢性淋巴增生性疾病的2%至6%，在亚洲人群中发病率略高。²临床上，患者常出现持续性血细胞减少，最显著的是中性粒细胞减少和贫血，可伴有复发性感染、脾肿大和一系列自身免疫表现，如类风湿性关节炎或干燥综合征。³与急性白血病不同，LGLL往往遵循缓慢、惰性的进展，但这掩盖了它对患者日常功能和长期健康的巨大影响。⁴

在最近的一项研究中，Yong-Guang Yang及其同事开发了一种严重免疫缺陷的猪模型，该模型支持人类造血干/祖细胞（HSPCs）的长期植入和多系分化。¹这一突破解决了当前人源化小鼠模型的关键限制，包括它们的小尺寸和有限的寿命，并为大规模生产人类免疫细胞提供了一个有前途的平台，有可能作为体内生物反应器发挥作用。