Leukemia research最新文献

Favorable outcomes with fludarabine, melphalan, and total-body irradiation 8–12Gy as an intensified conditioning regimen for adult allogeneic HCT 氟达拉滨、美法兰和8-12Gy全身照射作为成人同种异体HCT强化治疗方案的有利结果

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-02-04 DOI: 10.1016/j.leukres.2026.108183

Tomoyo Kubo , Hisashi Yamamoto , Otoya Watanabe , Yuki Taya , Aya Nishida , Shinsuke Takagi , Kyosuke Yamaguchi , Kosei Kageyama , Daisuke Kaji , Kazuya Ishiwata , Yuki Asano-Mori , Go Yamamoto , Atsushi Wake , Shuichi Taniguchi , Naoyuki Uchida

High-dose total body irradiation (TBI)–containing conditioning regimens remain an important strategy in allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed outcomes of adult patients who received Flu/Mel80/TBI 8–12 Gy at a single center. A total of 83 patients underwent their first allo-HCT between 2002 and 2023. The median age was 54 years; acute lymphoblastic leukemia accounted for 53 % of cases, and 45 % proceeded to transplantation in non-remission. Cord blood was used in 90 % of patients. At a median follow-up of 664 days among survivors, the 3-year overall survival (OS) and relapse-free survival (RFS) were 66.5 % and 59.5 %, respectively. The 3-year cumulative incidence of relapse was 24.0 %, and that of non-relapse mortality (NRM) was 16.5 %. In multivariate analysis, disease status at transplantation was the only factor significantly associated with RFS; no variables were significantly associated with OS, relapse, or NRM. Neutrophil engraftment was achieved in all patients, with a median of 16 days. Acute GVHD grade II–IV and III–IV by day 100 occurred in 64.4 % and 15.7 % of patients, respectively. The 3-year incidence of chronic GVHD was 19.4 %. In the cord blood subgroup, pre-engraftment immune reaction (PIR) occurred in 76 % of patients. In this high-risk cohort with a large proportion of non-remission, the Flu/Mel80/TBI 8–12 Gy regimen resulted in favorable engraftment, low relapse, and acceptable toxicity. These findings suggest that this intensified TBI-based conditioning may represent a viable option for patients requiring strong antitumor activity.

含高剂量全身照射（TBI）的调理方案仍然是同种异体造血细胞移植（allo-HCT）的重要策略。我们回顾性分析了在单个中心接受Flu/Mel80/TBI 8-12 Gy治疗的成年患者的结局。在2002年至2023年期间，共有83名患者接受了首次同种异体hct治疗。年龄中位数为54岁；急性淋巴细胞白血病占53 %的病例，45 %的患者在未缓解的情况下进行移植。90% %的患者使用脐带血。在幸存者中位664天的随访中，3年总生存率（OS）和无复发生存率（RFS）分别为66.5 %和59.5% %。3年累计复发率为24.0 %，非复发死亡率（NRM）为16.5 %。在多变量分析中，移植时的疾病状态是唯一与RFS显著相关的因素；没有变量与OS、复发或NRM显著相关。所有患者均实现了中性粒细胞移植，中位时间为16天。第100天急性GVHD II-IV级和III-IV级分别发生在64.4% %和15.7% %的患者中。慢性GVHD的3年发病率为19.4% %。在脐带血亚组中，76%的患者发生了移植前免疫反应（PIR） %。在这个高风险队列中，有很大比例的患者未缓解，Flu/Mel80/TBI 8-12 Gy方案导致了良好的植入，低复发率和可接受的毒性。这些发现表明，对于需要强抗肿瘤活性的患者来说，这种基于tbi的强化调理可能是一种可行的选择。

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引用次数: 0

CPX-351 versus venetoclax plus hypomethylating agents for newly diagnosed acute myeloid leukemia: A systematic review and meta-analysis CPX-351与venetoclax加低甲基化药物治疗新诊断的急性髓系白血病：一项系统回顾和荟萃分析

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-02-02 DOI: 10.1016/j.leukres.2026.108179

Akihiro Miyashita , Abdulrahim Mohammed Basendwah , Henri Fero , Fahad Alabbas

Acute myeloid leukemia (AML) predominantly affects older adults, with median age at diagnosis being 68–70 years. Selecting an appropriate regimen is important for older patients. CPX-351 demonstrated superior overall survival (OS) compared to 7 + 3 chemotherapy, while venetoclax and azacitidine significantly improved OS and composite remission rate compared to azacitidine alone. However, the optimal regimen in real-world practice remains uncertain. We performed a systematic review and meta-analysis comparing CPX-351 and the combination of venetoclax and hypomethylating agents (Ven/HMA) in newly diagnosed AML. We systematically searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2026. Eleven retrospective studies comprising 1852 patients comparing CPX-351 and Ven/HMA were included. The weighted mean of median age was 63.5 years in the CPX-351 cohort and 73 years in the Ven/HMA cohort. CPX-351 did not significantly improve OS (hazard ratio [HR] 0.89; 95 % CI 0.76–1.04; p = 0.1486) with median OS being 13.1 months versus 11.6 months in Ven/HMA cohort. There were no differences in the rates of composite remission rate (48.3 % vs 48.4 %; odds ratio [OR] 0.83; 95 % CI 0.58–1.18; p = 0.295), minimal residual disease negative remission (13.5 % vs 33.9 %; OR 0.61; 95 % CI 0.25–1.49; p = 0.281), 30-day mortality, and 60-day mortality. In conclusion, CPX-351 did not demonstrate superiority over Ven/HMA in composite remission rate and OS. Both regimens remain reasonable therapeutic options for older, newly diagnosed AML patients, and prospective comparative studies are needed to better guide treatment selection.

急性髓性白血病（AML）主要影响老年人，诊断时的中位年龄为68-70岁。选择合适的治疗方案对老年患者很重要。CPX-351与7（ + ）化疗相比显示出更高的总生存期（OS），而venetoclax和阿扎胞苷与单独阿扎胞苷相比显着提高了OS和复合缓解率。然而，在现实世界的实践中，最佳方案仍然不确定。我们进行了系统回顾和荟萃分析，比较CPX-351和venetoclax和低甲基化药物（Ven/HMA）联合治疗新诊断的AML。我们系统地检索了PubMed、Scopus和Cochrane Central Register of Controlled Trials从成立到2026年1月。11项回顾性研究包括1852例患者，比较CPX-351和Ven/HMA。CPX-351组的加权平均中位年龄为63.5岁，Ven/HMA组的加权平均中位年龄为73岁。CPX-351没有显著改善OS（风险比[HR] 0.89; 95 % CI 0.76-1.04; p = 0.1486），中位OS为13.1个月，而Ven/HMA队列为11.6个月。没有差异的复合缓解率(48.3 vs 48.4  % %;优势比[或]0.83;95年 %可信区间0.58 - -1.18;p = 0.295),微小残留病-缓解(13.5 vs 33.9  % %;或0.61;95年 %可信区间0.25 - -1.49;p = 0.281),30天死亡率和60天的死亡率。综上所述，CPX-351在综合缓解率和OS方面并不优于Ven/HMA。对于老年、新诊断的AML患者，这两种方案仍然是合理的治疗选择，需要前瞻性的比较研究来更好地指导治疗选择。

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引用次数: 0

Clonal hematopoiesis and age-associated degenerative disorders. 克隆造血和年龄相关退行性疾病。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-02-02 DOI: 10.1016/j.leukres.2026.108180

Ioannis Chanias, Michael Doulberis, Nicolas Bonadies

Clonal hematopoiesis (CH) is increasingly recognized not only as a predisposing factor for overt hematologic malignancies but also as a contributor to cardiovascular, metabolic, and other age-associated degenerative and inflammatory disorders. These associations likely arise from complex heterotypic interactions between clonally affected and non-clonal immune cells, leading to systemic immune dysregulation and chronic inflammation that affects multiple organ systems, most prominently the cardiovascular system. Somatic mutations typically linked to myeloid neoplasms disturb the inflammatory homeostasis of hematopoietic and immune compartments, resulting in a persistently heightened inflammatory state and exaggerated responses under stress conditions. Pattern-recognition receptors (PRRs) of the innate immune system detect pathogen- or damage-associated molecular patterns and activate supramolecular organizing centers (SMOCs) and downstream signaling cascades-including the inflammasome, myddosome, trifosome, necroptosome, and the TGF-β pathway-that drive the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IFN-I, and IL-6. Recent studies have begun to elucidate the mechanisms by which CH-associated mutations confer clonal advantage and dysregulate inflammatory signaling, bridging hematologic and degenerative diseases. A better understanding of these mechanistic links may facilitate the development of targeted therapies aimed at curbing clonal evolution and mitigating inflammation-driven comorbidities. In this review, we summarize the current knowledge on CH, its impact on immune dysregulation, and emerging therapeutic opportunities.

克隆造血（CH）越来越被认为不仅是明显的血液恶性肿瘤的诱发因素，而且也是心血管、代谢和其他与年龄相关的退行性和炎症性疾病的诱发因素。这些关联可能源于受克隆影响的免疫细胞和非克隆免疫细胞之间复杂的异型相互作用，导致系统性免疫失调和慢性炎症，影响多器官系统，最突出的是心血管系统。与髓系肿瘤相关的体细胞突变扰乱了造血和免疫区室的炎症稳态，导致炎症状态持续升高和应激条件下的过度反应。先天免疫系统的模式识别受体（PRRs）检测病原体或损伤相关的分子模式，并激活超分子组织中心（smoc）和下游信号级联——包括炎性小体、myddosome、三叶小体、坏死小体和TGF-β途径——驱动促炎细胞因子如IL-1β、TNF-α、IFN-I和IL-6的产生。最近的研究已经开始阐明ch相关突变赋予克隆优势和调节炎症信号，桥接血液学和退行性疾病的机制。更好地了解这些机制联系可能有助于开发靶向治疗，旨在抑制克隆进化和减轻炎症驱动的合并症。在这篇综述中，我们总结了目前关于CH的知识，它对免疫失调的影响，以及新兴的治疗机会。

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引用次数: 0

Juggling two worlds: Exploring the experiences of caregivers of patients with acute leukemia. 玩弄两个世界：探索急性白血病患者护理人员的经验。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-02-01 Epub Date: 2026-01-08 DOI: 10.1016/j.leukres.2025.108154

Maya A Stern, Elizaveta Klekovkina, Stephanie M Nanos, Esme Fuller-Thomson, Carmine Malfitano

Purpose: Caregiver burden is an often reported consequence of caring for patients with acute leukemia (AL). The current literature extensively describes caregiving tasks for patients with AL but provides limited information about the challenge of balancing these new obligations with previous and concurrent personal and family responsibilities. The goal of this qualitative study was to understand the multifaceted responsibilities of caregivers of patients with AL, their perceived impact, and the available resources that these caregivers found to be supportive in their caregiving role.

Methods: A secondary analysis, using qualitative description, was conducted on data obtained from interviews with 21 caregivers of children and adults with AL.

Results: Caregivers described balancing many responsibilities related to the patient, other relationships, work, and home. Coordinating and multitasking responsibilities were perceived to have an adverse effect on the emotional, physical, and financial well-being of participants. Social support was identified as a resource that supported the ability to manage the diverse responsibilities, and caregivers provided emotional and practical suggestions for care.

Conclusions: Upon becoming a caregiver for a patient with AL, individuals are faced with new responsibilities that compound their existing obligations, often resulting in the de-prioritization of the caregiver's needs and other responsibilities. The development and implementation of caregiver support as a standard of care is necessary to mitigate the negative consequences of caregiving.

目的：照顾者负担是经常报道的照顾急性白血病（AL）患者的后果。目前的文献广泛地描述了AL患者的护理任务，但提供的关于平衡这些新义务与先前和同时的个人和家庭责任的挑战的信息有限。本定性研究的目的是了解AL患者照护者的多方面责任，他们的感知影响，以及这些照护者发现在他们的照护角色中支持的可用资源。方法：采用定性描述的二次分析方法，对21名儿童和成人al护理人员的访谈数据进行了分析。结果：护理人员描述了与患者、其他关系、工作和家庭相关的许多责任的平衡。协调和多任务处理的责任被认为对参与者的情绪、身体和财务健康有不利影响。社会支持被认为是一种支持管理不同责任的能力的资源，照顾者为照顾提供情感和实际的建议。结论：在成为人工智能患者的照顾者后，个人面临着新的责任，这些责任与他们现有的义务相结合，往往导致照顾者的需求和其他责任的优先级降低。发展和实施作为护理标准的照顾者支持是必要的，以减轻照顾的负面后果。

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引用次数: 0

Calcium channel blocker use is associated with longer time to first post transfusion cardiac event in lower risk MDS 在低风险MDS患者中，钙通道阻滞剂的使用与输血后首次心脏事件发生时间较长相关

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-01-21 DOI: 10.1016/j.leukres.2026.108171

Carissa S.Y. Chan , Heather A. Leitch

引用次数: 0

Single cell transcriptomics derived combinatorial markers distinguished leukemic stem cells from hematopoietic stem cells in acute myeloid leukemia 单细胞转录组学衍生的组合标记在急性髓性白血病中区分白血病干细胞和造血干细胞

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-01-21 DOI: 10.1016/j.leukres.2026.108170

Aafreen Khan , Smeeta Gajendra , Vivek Kumar Singh , Deepshi Thakral , Sameer Bakhshi , Ranjit Kumar Sahoo , Rachna Seth , Sandeep Rai , Ritu Gupta

Leukemic stem cells (LSCs) play a critical role in relapse and chemoresistance in acute myeloid leukemia (AML). These LSCs originate from Hematopoietic stem cells (HSCs) after acquiring genetic and molecular aberrations. Both HSCs and LSCs predominantly reside in CD34 +CD38- fraction of the bone marrow and their phenotypic similarities poses a challenge in distinguishing between them. In addition, the phenotypic heterogeneity of LSCs limits the precise quantitation of this population in clinical studies. Delineation of LSCs from HSCs and quantification of LSC burden is crucial as it is correlated with survival rates and treatment outcomes in AML. In this study, we employed single cell transcriptomic analysis to identify differentially expressed cell surface markers that can discriminate LSCs from HSCs. Our data revealed several candidate markers, including CD48, CD52, CD96 and CD88 with distinct expression patterns in LSCs compared to HSCs. We further validated the expression levels of these markers as potential biomarkers for the identification of LSCs in both CD34 + and CD34- AML. Among these cell surface markers, CD52, CD96 and CD48 were significantly over-expressed in LSCs relative to HSCs. Incorporating these markers in combination with established aberrant markers can enhance the identification of LSCs and help distinguish them from HSCs in both CD34 + and CD34- AML. Our findings support the use of an expanded combinatorial marker panel and warrants its further evaluation in a larger AML cohort, particularly in the context of measurable residual disease (MRD) assessment, prognostication and correlation with treatment response and survival outcomes.

白血病干细胞（LSCs）在急性髓性白血病（AML）的复发和化疗耐药中起关键作用。这些LSCs是由造血干细胞（hsc）在获得遗传和分子畸变后产生的。造血干细胞和LSCs都主要存在于骨髓的CD34 +CD38-部分，它们的表型相似性给区分它们带来了挑战。此外，LSCs的表型异质性限制了临床研究中该群体的精确定量。从造血干细胞中分离LSCs和定量LSC负担是至关重要的，因为它与AML的存活率和治疗结果相关。在这项研究中，我们使用单细胞转录组学分析来鉴定可以区分LSCs和hsc的差异表达的细胞表面标记物。我们的数据揭示了几种候选标记物，包括CD48、CD52、CD96和CD88，与造血干细胞相比，它们在LSCs中的表达模式不同。我们进一步验证了这些标记物的表达水平，作为鉴定CD34 + 和CD34- AML中LSCs的潜在生物标志物。在这些细胞表面标记物中，相对于造血干细胞，CD52、CD96和CD48在LSCs中显著过表达。将这些标记与已建立的异常标记结合可以增强LSCs的识别，并有助于将它们与CD34 + 和CD34- AML中的hsc区分开来。我们的研究结果支持扩大组合标记面板的使用，并保证其在更大的AML队列中进一步评估，特别是在可测量残留疾病（MRD）评估、预后以及与治疗反应和生存结果的相关性方面。

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引用次数: 0

Impact of autoimmune diseases or inflammatory manifestations on response and outcome in high-risk myelodysplastic syndromes and chronic myelomonocytic leukemia 自身免疫性疾病或炎症表现对高危骨髓增生异常综合征和慢性骨髓单核细胞白血病的反应和结局的影响

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-01-16 DOI: 10.1016/j.leukres.2026.108168

Rinzine Sammut, Antoine Benichou, Chen Wang, Michael Loschi, Sami Benachour, Valentine Richez-Olivier, Edmond Chiche, Rami Komrokji, Corinne Ferrero-Vacher, Neila De Pooter, Joy Mouanes-Abelin, Bérengere Dadone-Montaudie, David A. Sallman , Thomas Cluzeau

引用次数: 0

The effect of IL-4 on CD180 expression and signalling in Chronic lymphocytic leukaemia (CLL) IL-4对慢性淋巴细胞白血病（CLL）中CD180表达及信号转导的影响

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-01-08 DOI: 10.1016/j.leukres.2026.108166

Ani Bilanishvili , Tamar Tsertsvadze , Kurtis Edwards , Sarah John-Olabode , Uzma Syed , Irina Datikashvili-David , Emanuela V. Volpi , John Murphy , Peter M. Lydyard , Nina Porakishvili

Chronic lymphocytic leukaemia (CLL) progression is critically dependent on tumour microenvironment (TME) signals, including those regulated via toll-like receptors (TLRs) that drive CLL cell survival and proliferation. We have previously shown that CD180, an orphan TLR is expressed on the surface in approximately 60 % of CLL samples, and that heterogeneity of CD180 cell surface expression and signalling impacts CLL cell survival, proliferation, and apoptosis. Interleukin-4 (IL-4), a cytokine abundantly present in the CLL microenvironment, is a well-documented pro-survival factor for CLL cells. IL-4 has also been shown to enhance sIgM expression and function by subsequent downstream signalling in a JAK3/STAT6 dependent manner within CLL samples. In this study, we investigated the impact of IL-4 on CD180 expression, CD180-mediated signalling and apoptosis of CLL cells and cell lines MEC-1 and RAMOS. Our results demonstrate that IL-4 enhances CD180 surface expression in CLL cells and RAMOS cell line, affecting downstream signalling pathways that alter CLL cell survival through the activation of AKT and p38MAPK. MEC-1 cells exhibited a less pronounced and variable response. These findings highlight the IL-4/CD180 axis as an important modulator of CLL, altering cell signalling dynamics.

慢性淋巴细胞白血病（CLL）的进展严重依赖于肿瘤微环境（TME）信号，包括那些通过toll样受体（TLRs）调节的信号，这些信号驱动CLL细胞的存活和增殖。我们之前已经表明，CD180，一个孤儿TLR在大约60% %的CLL样本的表面表达，并且CD180细胞表面表达和信号传导的异质性影响CLL细胞的存活、增殖和凋亡。白细胞介素-4 （IL-4）是一种在CLL微环境中大量存在的细胞因子，是CLL细胞的促生存因子。在CLL样本中，IL-4也被证明通过JAK3/STAT6依赖的方式通过随后的下游信号传导增强sIgM的表达和功能。在这项研究中，我们研究了IL-4对CLL细胞和细胞系MEC-1和RAMOS中CD180表达、CD180介导的信号传导和凋亡的影响。我们的研究结果表明，IL-4增强CLL细胞和RAMOS细胞系中CD180表面的表达，通过激活AKT和p38MAPK影响下游信号通路，从而改变CLL细胞的存活。MEC-1细胞表现出不太明显和可变的反应。这些发现强调了IL-4/CD180轴作为CLL的重要调制器，改变细胞信号动力学。

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引用次数: 0

Genomic profiles of myelodysplastic neoplasm with bone marrow eosinophilia or basophilia: Inflammatory drivers and DNA damage response 骨髓增生异常肿瘤伴骨髓嗜酸性粒细胞增多或嗜碱性粒细胞增多的基因组谱：炎症驱动因素和DNA损伤反应。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2026-01-01 DOI: 10.1016/j.leukres.2025.108156

Yujin Jung , Su Sung Kim , Sooyong Park , Dajeong Jeong , Ja-Yoon Gu , Jee-Soo Lee , Seon Young Kim , Yoon Hwan Chang , Moon-Woo Seong , Hongseok Yun , Hyun Kyung Kim

Background

Myelodysplastic neoplasms (MDS) are occasionally accompanied by bone marrow (BM) eosinophilia or basophilia. This study investigated molecular and cytogenetic characteristics and clinical implications of MDS with BM eosinophilia or basophilia as well as their prevalence.

Methods

A total of 464 MDS patients were evaluated for prevalence of BM eosinophilia or basophilia. A total of 74 MDS patients were included in the next-generation sequencing (NGS) testing, which was conducted on 90 candidate genes frequently found in hematologic malignancies. Fourteen patients exhibited BM eosinophilia (MDS-EOS), six patients displayed BM basophilia (MDS-BASO), fifty-five patients did not demonstrate eosinophilia or basophilia (MDS-/-), and only one satisfied both MDS-EOS and MDS-BASO. Cytogenetic abnormalities and overall survival were also investigated.

Results

MDS with BM eosinophilia or basophilia were observed in 7.33 % or 4.09 % of patients, respectively. MDS-EOS revealed significantly higher frequencies of mutations in ATM, TP53, CEBPA, FLT3 and DNA damage response (DDR) genes (ATM, PPM1D and TP53 combined). In MDS-BASO, significantly higher frequencies of mutations in ASXL1 and U2AF1 were shown. Variant allele frequency of DDR gene mutations significantly correlated with increased BM eosinophil fraction. Significant frequency of complex chromosomal abnormalities, especially involving chromosomes 5 and 7, was found in both MDS-EOS and MDS-BASO. MDS-EOS demonstrated significantly poorer survival rates than MDS-/-.

Conclusion

BM eosinophilia or basophilia was not uncommon. MDS with BM eosinophilia exhibited distinct mutational profiles including DDR genes mutations, which may attribute to adverse clinical outcomes. Identification of these subtypes can aid in prognosis and potentially guide targeted therapeutic approaches.

背景：骨髓增生异常肿瘤（MDS）偶尔伴有骨髓嗜酸性粒细胞增多或嗜碱性粒细胞增多。本研究探讨MDS伴嗜酸性粒细胞或嗜碱性粒细胞增多症的分子和细胞遗传学特征及临床意义。方法：对464例MDS患者进行嗜酸性粒细胞或嗜碱性粒细胞的患病率评估。共有74名MDS患者参与了下一代测序（NGS）测试，该测试对90个常见于血液恶性肿瘤的候选基因进行了检测。14例患者表现为骨髓嗜酸性粒细胞增多（MDS- eos）， 6例患者表现为骨髓嗜碱性粒细胞增多（MDS- baso）， 55例患者不表现为嗜酸性粒细胞增多或嗜碱性粒细胞增多（MDS-/-），只有1例患者同时满足MDS- eos和MDS- baso。细胞遗传学异常和总生存率也进行了调查。结果：MDS合并BM嗜酸性粒细胞增多（7.33% %）或嗜碱性粒细胞增多（4.09 %）。MDS-EOS显示ATM、TP53、CEBPA、FLT3和DNA损伤反应（DDR）基因（ATM、PPM1D和TP53组合）的突变频率显著较高。在MDS-BASO中，ASXL1和U2AF1的突变频率明显更高。DDR基因突变的变异等位基因频率与BM嗜酸性粒细胞比例增加显著相关。在MDS-EOS和MDS-BASO中均发现复杂染色体异常的显著频率，特别是涉及5号和7号染色体。MDS- eos的生存率明显低于MDS-/-。结论：BM嗜酸性粒细胞增多或嗜碱性粒细胞增多并不少见。MDS伴BM嗜酸性粒细胞增多表现出不同的突变谱，包括DDR基因突变，这可能归因于不良的临床结果。识别这些亚型有助于预后，并可能指导有针对性的治疗方法。

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引用次数: 0

Outcomes of two distinct T-cell depletion strategies in haploidentical vs unrelated donor pediatric HSCT: A single-center retrospective analysis 两种不同的t细胞消耗策略在单倍体与非相关供体儿童HSCT中的结果：一项单中心回顾性分析

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-12-23 DOI: 10.1016/j.leukres.2025.108150

Luisa Sisinni , Odelaisy León-Triana , Mikel Fernandez Artazcoz , Mauro Guariento , Iñigo Figueroa Real de Asua , Yasmina Mozo del Castillo , Paula Lazaro del Campo , David Bueno Sanchez , Carmen Mestre Durán , Jordi Minguillón Pedreño , Mercedes Gasior Kabat , Antonio Pérez-Martínez

We conducted a single-center retrospective analysis of 49 consecutive pediatric and AYA (adolescent and young adult) patients who underwent either T-cell receptor alpha/beta and CD19-depleted unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) (TCRαβ/CD19-depleted URD HSCT; n = 22, including 13 matched unrelated donors [MUD] and 9 mismatched unrelated donors [MMUD]) or CD45RA⁺-depleted haploidentical (HAPLO) HSCT (CD45RA⁺-depleted HAPLO HSCT; n = 27) between 2018 and 2023 for malignant hematological disorders. Both groups showed comparable engraftment kinetics. Primary graft failure occurred in four patients (8.5 %), predominantly in the HAPLO group. Acute graft-versus-host disease (aGvHD) grade II–IV occurred in 72.9 % of patients, with the highest incidence in the MMUD subgroup (89 %; p = 0.03). Chronic GvHD (cGvHD) was observed in 42.6 % of patients, with a tendency toward a higher incidence in the MMUD group (67 % vs 38 % for MUD and 33 % for HAPLO; p = 0.08). The 2-year overall survival (OS) was 75.5 %, with no significant differences between groups (MUD 92.3 %, MMUD 77.7 %, HAPLO 66.6 %; p = 0.34). GvHD-free/relapse-free survival (GRFS) at 2 years favored MUD (51.9 %) and HAPLO (51.3 %) over MMUD (22.2 %), with significantly poorer GRFS in MMUD compared with HAPLO (p = 0.038). In multivariate analysis, disease status ≥ third complete remission (≥CR3) at HSCT was associated with significantly poorer OS (hazard ratio [HR] 13, 95 % confidence interval [CI] 1.2–130; p = 0.036), while sex mismatch (female donor to male recipient) was associated with inferior GRFS (HR 4.5, 95 % CI 1.6–12; p = 0.0035). Our results highlight the feasibility of both HAPLO and URD HSCT in children with malignancies, using distinct T-cell depletion strategies tailored to donor type. However, our findings also indicate that ex vivo T-cell depletion alone, without additional GvHD prophylaxis, is insufficient to prevent GvHD, underscoring the need for combined strategies to improve outcomes.

我们对49名连续接受t细胞受体α / β和cd19缺失非相关供体（URD）造血干细胞移植（HSCT）（TCRαβ/ cd19缺失URD HSCT； n = 22，包括13名匹配的非相关供体[MUD]和9名错配的非相关供体[MMUD]）或CD45RA + -缺失HAPLO HSCT (CD45RA + -缺失HAPLO HSCT；N = 27)在2018年至2023年恶性血液病。两组的移植物动力学相当。4例患者发生原发性移植物衰竭（8.5 %），主要发生在HAPLO组。急性移植物抗宿主病（aGvHD） II-IV级发生率为72.9 %，其中MMUD亚组发生率最高（89 %;p = 0.03）。慢性GvHD （cGvHD）在42.6 %的患者中观察到，MMUD组的发病率有更高的趋势（67 % vs 38 % MUD和33 % HAPLO； p = 0.08）。2年总生存率（OS）为75.5 %，组间差异无统计学意义（MUD 92.3 %,MMUD 77.7 %,HAPLO 66.6 %;p = 0.34）。2年无gvhd /无复发生存率（GRFS）在MUD（51.9 %）和HAPLO（51.3 %）优于MMUD(22.2% %)，MMUD的GRFS明显低于HAPLO （p = 0.038）。在多变量分析中，HSCT的疾病状态≥ 第三次完全缓解（≥CR3）与较差的OS相关（风险比[HR] 13,95 %置信区间[CI] 1.2-130; p = 0.036），而性别不匹配（女性供体与男性受体）与较差的GRFS相关（HR 4.5, 95 % CI 1.6-12; p = 0.0035）。我们的研究结果强调了HAPLO和URD HSCT在儿童恶性肿瘤中的可行性，使用针对供体类型量身定制的不同t细胞消耗策略。然而，我们的研究结果也表明，单独的体外t细胞消耗，没有额外的GvHD预防，不足以预防GvHD，强调需要联合策略来改善结果。

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