Leukemia Research Reports最新文献

英文中文

Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma 高剂量美伐兰后自体干细胞移植治疗依赖透析的多发性骨髓瘤患者的药代动力学和疗效

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100522

Rabea Mecklenbrauck , Bernhard M.W. Schmidt , Heike Bähre , Annamaria Brioli , Arnold Ganser , Florian H. Heidel , Felicitas Thol

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for fit patients with multiple myeloma (MM). However, individuals who are dependent on hemodialysis are frequently excluded from ASCT. Recommendations on chemotherapy dosing and hemodialysis scheduling vary in literature and definite conclusions are impeded by the heterogeneity of cohorts.

We aimed to evaluate the safety and efficacy of ASCT in patients with MM and end-stage renal disease and to examine the pharmacokinetics of melphalan on a fixed schedule of melphalan infusion and hemodialysis.

The outcome of 13 patients undergoing ASCT while being on hemodialysis between 2000 and 2022 was retrospectively analysed and compared to matched hemodialysis-independent patients. Melphalan plasma concentrations were measured in 4 hemodialysis-dependent and 5 independent patients.

Plasma concentrations of hemodialysis-dependent patients were comparable to hemodialysis-independent patients with a 6-hour interval between melphalan infusion and hemodialysis (p = 0.9). The rate of immediate side effects of high-dose melphalan was significantly higher in 13 dialysis-dependent patients compared to 47 matched controls despite not having prolonged neutropenia (p = 0.9). Overall survival both from d₀ of ASCT and diagnosis was comparable (p = 0.33 and p = 0.17, respectively).

Thus, adopting the proposed schedule and management of immediate side effects make ASCT a safe option for myeloma patients with end-stage renal disease.

高剂量美法兰后自体干细胞移植（ASCT）仍然是适合多发性骨髓瘤（MM）患者的标准治疗方法。然而，依赖血液透析的个体经常被排除在ASCT之外。关于化疗剂量和血液透析计划的建议在文献中有所不同，并且由于队列的异质性，明确的结论受到阻碍。我们的目的是评估ASCT在MM和终末期肾病患者中的安全性和有效性，并在固定时间表的美伐兰输注和血液透析中检查美伐兰的药代动力学。回顾性分析了2000年至2022年间13例接受ASCT同时进行血液透析的患者的结果，并与匹配的不进行血液透析的患者进行了比较。测定4例血液透析依赖患者和5例血液透析独立患者的血浆浓度。在美法兰输注和血液透析间隔6小时时，血液透析依赖患者的血药浓度与血液透析独立患者相当（p = 0.9）。高剂量美法兰的即时副作用率在13名透析依赖患者中显著高于47名匹配对照，尽管没有长期中性粒细胞减少症（p = 0.9）。ASCT 0和诊断的总生存率相当（p = 0.33和p = 0.17）。因此，采用建议的时间表和即时副作用的管理使ASCT成为骨髓瘤终末期肾脏疾病患者的安全选择。

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引用次数: 0

Unveiling prognosis in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax through novel risk stratification 通过新的风险分层揭示低甲基化药物和venetoclax治疗急性髓系白血病患者的预后

IF 0.9 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100550

Jiajia Sun, Zhiping Guo

Several genetic risk classification systems based on response to older acute myeloid leukemia patients treated with less-intensive regimens, especially venetoclax (VEN) + hypomethylating agent (HMA), are proposed recently. VEN+HMA improved the outcome of cytogenetic adverse-risk AML, AML with some of MR mutations and/or clonal hematopoiesis (CH) related mutations. DNMT3A^mut, IDH1/2^mut and NPM1^mut were defined as “VEN sensitive mutations”. DDX41^mut is identified as a particularly favorable-risk group. Even multi-hit TP53 status did not negatively affect overall survival (OS) of DDX41-mutants. Signaling gene mutations (FLT3-ITD^pos and K/NRAS^mut) are classified as intermediate risk, consistent with their biological associations as mediators of VEN resistance.

最近提出了几种基于老年急性髓系白血病患者对低强度治疗方案的反应的遗传风险分类系统，特别是venetoclax (VEN) +低甲基化剂（HMA）。VEN+HMA改善了细胞遗传学不良风险AML、一些MR突变和/或克隆造血（CH）相关突变的AML的预后。DNMT3Amut、IDH1/2mut和NPM1mut被定义为“VEN敏感突变”。DDX41mut被认为是一个特别有利的风险群体。即使多次命中TP53状态也不会对ddx41突变体的总生存期（OS）产生负面影响。信号基因突变（FLT3-ITDpos和K/NRASmut）被归类为中等风险，与它们作为VEN耐药介质的生物学关联一致。

引用次数: 0

Baseline erythropoietin level predicts Luspatercept response in Chinese patients with myelodysplastic syndrome: a propensity score-matched analysis 基线促红细胞生成素水平预测中国骨髓增生异常综合征患者的Luspatercept反应：倾向评分匹配分析

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100532

Doudou Chang , Junyan Zhang , Meiling Zhao , Xialin Zhang , Jia Wei , Ruijuan Zhang

Background

Luspatercept is a novel erythroid maturation agent approved for treating transfusion-dependent anemia in myelodysplastic syndrome (MDS). However, predictive biomarkers and real-world data in Asian populations remain limited.

Methods

We conducted a retrospective cohort study of 66 MDS patients from two Chinese centers, including 22 patients treated with luspatercept and 44 matched controls. Propensity score matching (1:2) was used to adjust for age, sex, risk category, baseline hemoglobin, transfusion burden, and erythropoietin (EPO) levels. Primary endpoints were red blood cell transfusion independence (RBC-TI) ≥8 weeks and hematologic improvement–erythroid (HI-E).

Results

By week 12, 54.5 % of luspatercept-treated patients achieved RBC-TI, compared to 29.5 % in the control group (P < 0.05). Patients with baseline EPO <500 IU/mL had higher RBC-TI rates than those with EPO ≥500 IU/mL (63.6 % vs. 45.5 %). Multivariate analysis identified baseline EPO <500 IU/mL as an independent predictor of response (OR=2.36, 95 % CI: 1.24–4.52, P = 0.008). Safety was acceptable, with no treatment discontinuation due to adverse events.

Conclusion

This first matched real-world study of luspatercept in Chinese MDS patients confirms its efficacy in reducing transfusion needs and identifies baseline erythropoietin level as a clinically meaningful predictor of response. These findings support the integration of EPO-guided selection in personalized treatment strategies.

背景：luspatercept是一种新的红细胞成熟剂，被批准用于治疗骨髓增生异常综合征（MDS）的输血依赖性贫血。然而，亚洲人群的预测性生物标志物和实际数据仍然有限。方法我们对来自中国两个中心的66例MDS患者进行回顾性队列研究，包括22例接受luspaterceept治疗的患者和44例匹配的对照组。倾向评分匹配（1:2）用于调整年龄、性别、风险类别、基线血红蛋白、输血负担和促红细胞生成素（EPO）水平。主要终点为红细胞输血独立性(RBC-TI)≥8周和血液学改善-红细胞（HI-E）。结果到第12周，54.5%的luspaterept治疗患者达到了RBC-TI，而对照组为29.5% (P <；0.05)。基线EPO和lt为500 IU/mL的患者比EPO≥500 IU/mL的患者有更高的RBC-TI率（63.6%对45.5%）。多变量分析确定基线EPO和lt 500 IU/mL是反应的独立预测因子（OR=2.36, 95% CI: 1.24-4.52, P = 0.008）。安全性是可接受的，没有因不良事件而中断治疗。本研究首次在中国MDS患者中应用luspatercept，证实了其减少输血需求的有效性，并确定了基线促红细胞生成素水平是临床有意义的反应预测指标。这些发现支持将epo引导的选择纳入个性化治疗策略。

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引用次数: 0

Real-World Efficacy and Safety of Gemtuzumab Ozogamycin (GO) and 3 + 7 regimen in fit newly diagnosed Acute Myeloid Leukemia (AML) patients. A Retrospective multicenter study of “Rete Ematologica Pugliese” (REP) Gemtuzumab Ozogamycin （GO）和3 + 7方案在适合新诊断的急性髓性白血病（AML）患者中的实际疗效和安全性“Pugliese Rete emat”（REP）的多中心回顾性研究

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100525

M. Dargenio , C. Buquicchio , D. Pastore , L. Aprile , L. Ciuffreda , G. Greco , M. Delia , V. Federico , MP. Fina , D. Seripa , R. Matera , G. Tarantini , A. Maggi , L. Melillo , V. Pavone , P. Musto , G. Specchia , N. Di Renzo

Gemtuzumab Ozogamicin, a monoclonal antibody targeting CD33, linked to calicheamicin, is approved in combination with “3 + 7″ for the treatment of patients with de novo CD33 positive AML. The aim of study was to evaluate the outcome of patients receiving 3 + 7 plus GO as front-line therapy outside clinical trials. Between March 2020 and February 2023, 34 consecutive fit CD33+ AML patients, median age 54.5 years (range, 25–75) were treated. This study confirms the efficacy and toxicity data reported in clinical trials, highlighting the feasibility of GO based chemotherapy also in patients older than 60 years and as a bridge to allo-HSCT.

Gemtuzumab Ozogamicin是一种靶向CD33的单克隆抗体，与calicheamicin相连，被批准与“3 + 7″”联合用于治疗新发CD33阳性AML患者。本研究的目的是评估接受3 + 7 +氧化石墨烯作为临床试验外一线治疗的患者的结果。在2020年3月至2023年2月期间，连续治疗了34例CD33+ AML患者，中位年龄54.5岁（范围25-75岁）。本研究证实了临床试验中报告的疗效和毒性数据，强调了氧化石墨烯为基础的化疗在60岁以上患者中的可行性，并作为异位造血干细胞移植的桥梁。

引用次数: 0

The synergistic effect of 2-deoxy-D-glucose and cytarabine on mitochondria of stem-like cells derived from KG1-a 2-脱氧-d -葡萄糖和阿糖胞苷对KG1-a源性干细胞线粒体的协同作用

IF 0.9 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100537

Sona Rezaei , Mohammad Mohammadzadeh-Vardin , Keyvan Amirshahrokhi , Mojtaba Amani

Acute myeloid leukemia (AML) often relapses post-chemotherapy due to leukemia stem cells (LSCs), which rely on mitochondria for energy, ROS regulation, and apoptosis. Targeting mitochondrial pathways may overcome LSC resistance. This study evaluated Cytarabine (Ara-C), 2-Deoxy-d-Glucose (2-DG), and their combination on AML-derived KG1-a cells using MTT assays, showing reduced viability with combined treatment. The Magnetic sorting isolated CD34+ (stem-like) and CD34- cells. Flow cytometry revealed increased ROS and decreased mitochondrial membrane potential (MMP) in KG1-a and CD34+ cells with 2-DG and Ara-C, suggesting a promising strategy to target resistant LSCs in AML therapy.

急性髓性白血病（AML）化疗后经常复发，这是由于白血病干细胞（LSCs）依赖线粒体提供能量、ROS调节和细胞凋亡。靶向线粒体途径可能克服LSC抗性。本研究利用MTT法评估了阿糖胞苷（Ara-C）、2-脱氧-d-葡萄糖（2-DG）及其联合治疗对aml衍生的KG1-a细胞的影响，结果显示联合治疗降低了KG1-a细胞的存活率。磁分选分离CD34+（干样）和CD34-细胞。流式细胞术显示，含2-DG和Ara-C的KG1-a和CD34+细胞中ROS增加，线粒体膜电位（MMP）降低，提示靶向耐药LSCs治疗AML的有希望的策略。

引用次数: 0

Rapid development of Philadelphia chromosome-negative AML in a CML patient with sustained major molecular response to tyrosine kinase inhibitor therapy 在对酪氨酸激酶抑制剂治疗持续主要分子反应的CML患者中，费城染色体阴性AML的快速发展

IF 0.9 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100536

Huan Liu , Yunxia Sun , Liangliang Li , Yurong Zhang , Yaxiong Zhou , Pengyun Zeng , Lingling Yue

The use of TKIs has significantly improved the prognosis of CML. However, a small subset of patients still experience poor outcomes. We present a rare case of Ph-AML following a diagnosis of CML. The patient achieved CCyR and MMR after 4 months of nilotinib therapy, with sustained deep remission for 3 years. Unexpectedly, the disease developed rapidly to AML. Further investigations revealed the emergence of CCA/Ph- and gene mutations. We retrospectively analyzed previous CML patients with BCR::ABL1 and Ph-negative status in blast crisis from our database and conducted a comprehensive review of the relevant literature.

TKIs的使用显著改善了CML的预后。然而，一小部分患者的预后仍然很差。我们提出一个罕见的病例Ph-AML后诊断为CML。患者在尼罗替尼治疗4个月后达到CCyR和MMR，持续深度缓解3年。出乎意料的是，疾病迅速发展为急性髓性白血病。进一步的研究发现出现了CCA/Ph-和基因突变。我们回顾性分析了我们数据库中BCR::ABL1和ph阴性的原发性危象CML患者，并对相关文献进行了全面的回顾。

引用次数: 0

Le lymphome cutanée primitif diffus à grandes cellules B : à propos d’un cas Primary cutaneous diffuse large B-cell lymphoma: a case report 原发性皮肤弥漫性大B细胞淋巴瘤：病例报告

IF 0.9 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100538

Mustapha Mechtoune , Fatima Zahra Lahlimi , Illias Tazi , Hanane Rais , Houda Jouihri , Mohammed el Fadli

The association of cutaneous B-cell lymphoma and dermatofibrosarcoma is exceptional. We report the case of a 44-year-old patient with a history of Darier-Ferrand dermatofibrosarcoma who presented with cutaneous B-cell lymphoma characterized by large atypical skin lesions with an aggressive course. The patient was treated with a combination of RCHOP-type chemotherapy and surgical treatment. We shed light on this very rare association whose prognosis depends on early diagnosis and adequate management.

皮肤b细胞淋巴瘤和皮肤纤维肉瘤的关联是例外的。我们报告一例44岁的达利尔-费朗皮肤纤维肉瘤患者，其表现为皮肤b细胞淋巴瘤，其特征是大的非典型皮肤病变，具有侵袭性病程。患者采用rchop型化疗联合手术治疗。我们阐明了这种非常罕见的关联，其预后取决于早期诊断和适当的管理。

引用次数: 0

Asciminib and inotuzumab ozogamicin: a new combination for highly refractory Ph-positive B-cell acute lymphoblastic leukemia 阿西米尼和inotuzumab ozogamicin：一种治疗高度难治性ph阳性b细胞急性淋巴细胞白血病的新组合

IF 0.9 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100546

Aneta Strumilowska , Katherine Devitt , Joanna Conant , Juli-Anne Gardner , Ashley Volaric , Neel Hegde , Diego Adrianzen-Herrera

引用次数: 0

Trans-differentiation of plasma cell neoplasm to acute myeloid leukemia with monocytic features: Case report of divergent phenotype with identical genotype 浆细胞肿瘤向具有单核细胞特征的急性髓系白血病的反分化：基因型相同但表型不同的病例报告

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100504

Saja Asakrah , Kristin K. Deeb , Nikolaos Papadantonakis , George Deeb

Myeloid malignancies following treatment for plasma cell neoplasms (PCN) are infrequent but is a serious complication, often exhibiting complex karyotype and TP53 mutations. Plasma cell myeloma lineage switch to a myeloid malignancy with evident clonal relatedness is seldomly reported. Here, we report a unique case of acute myeloid leukemia with monocytic differentiation that shares clonal features with an antecedent plasma cell myeloma with t(4;14)(FGFR3::IGH). This phenomenon differs from therapy-related myeloid neoplasm arising from an unrelated clone and underscores the need to elucidate the role of mutations in pathways such as MAPK (e.g., BRAF and KRAS) into lineage plasticity.

浆细胞肿瘤（PCN）治疗后出现髓系恶性肿瘤并不常见，但却是一种严重的并发症，通常表现为复杂的核型和TP53突变。浆细胞骨髓瘤谱系转换为髓系恶性肿瘤与明显的克隆相关性很少报道。在这里，我们报告了一例独特的单核细胞分化急性髓性白血病，其克隆特征与先前的t（4;14）浆细胞骨髓瘤（FGFR3::IGH）相同。这种现象不同于由不相关克隆引起的治疗相关髓系肿瘤，强调了阐明MAPK（例如BRAF和KRAS）等通路突变在谱系可塑性中的作用的必要性。

引用次数: 0

The road not taken: Exploring non-transplant options in De Novo philadelphia positive acute myeloid leukemia 未采取的道路：探索非移植选择在De Novo费城阳性急性髓性白血病

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports

Pub Date : 2025-01-01 DOI: 10.1016/j.lrr.2025.100507

Mohamed I Sharif, Ahmad S. Alotaibi, Ruah Alyamany, Ali Alahmari, Hanan Alkhaldi, Ayman Saad, Mansour Alfayez

Acute myeloid leukemia (AML) is a heterogeneous disease with diverse molecular cytogenetic characteristics. Philadelphia-positive acute myeloid leukemia, a rare subtype of AML, is traditionally considered a high-risk, with the standard recommendation being an allogeneic hematopoietic cell transplant (HCT) in first remission. More recently, with better characterization and understanding of AML biology, novel therapies have been introduced. Drawing parallels from the advances seen in Philadelphia-positive acute lymphoblastic leukemia (ALL), the question arises whether potent tyrosine kinase inhibitors (TKI), such as ponatinib, in combination with AML-directed therapies, could be used in Philadelphia-positive AML, potentially eliminating the need for HCT in the first remission.

In this report, we review the literature on Philadelphia-positive AML, study a case where HCT was omitted, and explore potential signals that could support successful HCT omission.

急性髓性白血病（AML）是一种具有多种分子细胞遗传学特征的异质性疾病。费城阳性急性髓性白血病是一种罕见的急性髓性白血病亚型，传统上被认为是高风险的，标准建议在首次缓解时进行同种异体造血细胞移植（HCT）。最近，随着对AML生物学的更好的描述和理解，新的治疗方法被引入。与费城阳性急性淋巴细胞白血病（ALL）的进展相似，问题出现了，是否有效的酪氨酸激酶抑制剂（TKI），如ponatinib，与AML靶向治疗联合，可以用于费城阳性AML，潜在地消除首次缓解时对HCT的需求。在本报告中，我们回顾了费城阳性AML的文献，研究了一个遗漏HCT的病例，并探讨了可能支持成功遗漏HCT的潜在信号。

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