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Successful Treatment with Daratumumab of a Patient with Monoclonal Lambda Light Chain Disease Presenting as Nephrotic Syndrome and Crescentic Glomerulonephritis. 用达拉姆单抗成功治疗了一名表现为肾病综合征和新月体肾小球肾炎的单克隆λ轻链病患者。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2024-01-16 DOI: 10.1159/000536283
Alon Bnaya, Chezi Ganzel, Linda Shavit

Introduction: Monoclonal immunoglobulin deposition diseases (MIDDs) are a group of systemic diseases, characterized by deposition of monoclonal immunoglobulin predominantly in the kidney. In the absence of overt hematologic disease, MIDDs are classified as a part of monoclonal gammopathy of renal significance. Patients with MIDD may present with a nephrotic syndrome and kidney function impairment. Treatment usually includes anti-plasma cell therapy.

Case presentation: We report a case of a 54-year-old female who presented with nephrotic syndrome related to light chain deposition disease of lambda type. Due to a complicated clinical course (including cardiac injury and thromboembolic stroke), plasma cell-targeted therapy was stopped. A few months later, the patient presented with severe acute kidney injury. Kidney biopsy revealed crescentic glomerulonephritis, and immunofluorescence staining was positive for lambda chain. Treatment with daratumumab was initiated resulting in stabilization of kidney function and partial nephrotic syndrome remission.

Conclusion: This case highlights an uncommon histologic manifestation in a patient diagnosed with light chain deposition disease. Furthermore, it underscores the significance of plasma cell-targeted therapy and the favorable clinical and hematological response observed with daratumumab.

单克隆免疫球蛋白沉积病(MIDD)是一组全身性疾病,其特征是单克隆免疫球蛋白主要沉积在肾脏。在没有明显血液病的情况下,MIDD 被归类为具有肾脏意义的单克隆丙种球蛋白病的一部分。MIDD 患者可能会出现肾病综合征和肾功能损害。治疗通常包括抗浆细胞治疗。在此,我们报告了一例 54 岁女性患者的病例,她出现了与λ型轻链沉积病相关的肾病综合征。由于复杂的临床过程(包括心脏损伤和血栓栓塞性中风),患者停止了浆细胞靶向治疗。几个月后,患者出现了严重的急性肾损伤。肾活检发现新月体性肾小球肾炎,免疫荧光染色显示λ链阳性。患者开始接受达拉单抗治疗,结果肾功能趋于稳定,肾病综合征得到部分缓解。
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引用次数: 0
Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents. 新型药物时代的慢性淋巴细胞白血病加速和里氏转化。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-09-04 DOI: 10.1159/000533664
Ilana Levy Yurkovski, Tamar Tadmor

Background: Tremendous developments in the field of chronic lymphocytic leukemia (CLL) in recent years have led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to "accelerated CLL" (A-CLL) or to "Richter transformation" (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis and therapy. In the current review, we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations.

Summary: A-CLL is a rare and underdiagnosed entity that probably stands in the "gray zone" between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi), are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies [BiTe] or the chimeric antigen receptor [CAR] technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials.

Key messages: The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of "unmet need" and require further studies to identify the best diagnostic approach and a more effective treatment.

背景:近年来,慢性淋巴细胞白血病(CLL)领域取得了巨大的发展,导致治疗方法发生了革命性的变化,如今的治疗方法以靶向治疗为基础,具有良好的反应和最佳的预后。尽管如此,CLL 仍有可能发展为 "加速型 CLL"(A-CLL)或 "里克特转化"(RT),这两种实体的病程更具侵袭性,在诊断和治疗领域仍面临挑战。在本综述中,我们总结了 A-CLL 诊断方法、现有治疗方法和临床试验方面的最新知识,A-CLL 和 RT 仍有未满足的需求,需要进行更多的基础和临床研究。摘要:A-CLL 是一种罕见且诊断不足的疾病,可能处于 CLL 和 RT 之间的 "灰色地带",预后一般处于中等水平。其诊断主要基于组织学发现,包括增殖中心扩大、有丝分裂活动增加和/或高 Ki-67 指数。由于其罕见性,其治疗方法仍未确定,但新型药物,尤其是布鲁顿酪氨酸激酶抑制剂(BTKi)似乎很有效。至于 RT,标准疗法仍包括化疗免疫疗法,然后对预后不良的合适应答者进行干细胞移植。最近采用的新方法包括通过新型药物(BTKi、venetoclax)抑制B细胞、T细胞吞噬(检查点抑制剂、双特异性抗体[BiTe]或嵌合抗原受体[CAR]技术)、抗体药物共轭物或药物组合。虽然CAR-T和BiTe似乎都很有前景,尤其是与BTKi联合使用时,但目前证据仍不充分,临床试验一般应招募患者:CLL领域近年来取得了重大进展,但A-CLL和RT仍是 "未满足需求 "的主题,需要进一步研究以确定最佳诊断方法和更有效的治疗方法。
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引用次数: 0
Importance of Minimal Residual Disease in the Era of Targeted Therapies in Chronic Lymphocytic Leukemia. MRD在CLL靶向治疗时代的重要性。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-10-30 DOI: 10.1159/000534846
Othman Al-Sawaf

Background: The level of minimal residual disease (MRD), often binarized into detectable or undetectable MRD according to certain thresholds, is strongly associated with long-term outcomes after chemo- and chemoimmunotherapy.

Summary: Driven by our improved understanding of the biology of chronic lymphocytic leukemia (CLL), the recent decade has shown a shift from chemotherapy-based regimens to regimens based on targeted agents that exploit distinct biological vulnerabilities of CLL. These targeted agents can be broadly classified into inhibitors of Bruton tyrosine kinase (BTK) and BCL2 as well as CD20-directed antibodies. Depending on which agent and which combination of agents is used, the levels or status of MRD can have varying clinical relevance. This has implications on the prognosis after therapy as well as on possible strategies to guide treatment duration and intensity.

Key messages: This review summarizes the main discoveries related to MRD in the context of targeted therapies. Furthermore, it provides an overview on current hurdles and caveats related to the implementation of MRD in regular clinical care and summarize open research questions that need to be addressed with future clinical studies.

最小残留疾病(MRD)的水平,通常根据某些阈值二值化为可检测或不可检测的MRD,与化疗和化学免疫治疗后的长期结果密切相关。在我们对CLL生物学理解的提高的推动下,最近十年显示出从基于化疗的方案向基于靶向药物的方案的转变,这些靶向药物利用了CLL的不同生物学脆弱性。这些靶向药物可广泛分为布鲁顿酪氨酸激酶(BTK)和BCL2抑制剂以及CD20定向抗体。根据所使用的制剂和制剂的组合,MRD的水平或状态可能具有不同的临床相关性。这对治疗后的预后以及指导治疗持续时间和强度的可能策略都有影响。这篇综述总结了在靶向治疗的背景下与MRD相关的主要发现。此外,它概述了目前在常规临床护理中实施MRD的障碍和注意事项,并总结了未来临床研究需要解决的开放性研究问题。
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引用次数: 0
Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide. 用多重蛋白质组学鉴定接受非布鲁肽治疗的异体造血细胞移植患者极重度窦道阻塞综合征/静脉闭塞性疾病(SOS/VOD)的潜在生物标记物。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2024-02-08 DOI: 10.1159/000535706
Ram Vasudevan Nampoothiri, Lisa Avery, Ivan Pasic, Ioannis Prassas, Eleftherios Diamandis, Fotios V Michelis

Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers.

Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot.

Results: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD.

Conclusion: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD.

引言 尽管异基因造血干细胞移植后 SOS/VOD 的临床诊断标准已经确立,但仍缺乏确定的诊断性蛋白质生物标志物。方法 对极重度 SOS/VOD 患者进行前瞻性样本采集,采集时间为诊断时以及开始使用去纤维化药物后的第 3、7、14 和 30 天。在同种异体 HCT 后第 +14、+30、+60、+90 和 +180天采集了年龄匹配的无 VOD 对照组样本。通过基于抗体的近距离延伸测定(PEA)分析血清样本中的 2925 蛋白水平。在火山图中使用 t 检验比较对数变换丰度值的平均差异。结果 比较了五名极重度 SOS/VOD 患者和五名对照组患者。结果发现,有 10 种蛋白质的浓度出现了对数转换后的 3 倍增长,具有显著的统计学意义。它们是 CALCA、CCL20、GPR37、IGFBP4、IL1RL1、SLC39A14、SPINK4、FABP3、MYL3 和 CHCHD10。四种不同的蛋白质,即 CD83、LAIR2、CD7 和 HEM6 在接受去纤维化治疗后出现显著下降。80%(n=4)的患者的 SOS/VOD 病症得到缓解,而一名患者因 SOS/VOD 病症死亡。结论 PEA 技术发现了 10 种在极重度 SOS/VOD 患者中明显升高的蛋白质。使用该技术在更大的群体中进行前瞻性研究,也许能最终确定 SOS/VOD 的诊断性蛋白质生物标志物。
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引用次数: 0
Fluoroquinolone Prophylaxis during Conventional Chemotherapy or Hematopoietic Stem Cell Transplantation for Acute Leukemia - Pros and Cons. 急性白血病常规化疗或造血干细胞移植期间氟喹诺酮类药物的预防——利弊。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-11-21 DOI: 10.1159/000535119
Tomer Hoffman, Alaa Atamna, Vladislav Litchevsky, Irina Amitai, Dafna Yahav

Background: Prophylaxis with fluoroquinolones (FQ) is commonly used in patients with acute leukemia (AL) during neutropenia. This practice is supported by an older meta-analysis reporting reduced mortality using FQ prophylaxis. Later meta-analyses have failed to reproduce this finding, presumably due to higher background FQ resistance rates limiting their effectiveness.

Summary: This article reviews the pros and cons of FQ prophylaxis mainly in patients with AL. Most current guidelines do not support universal prophylaxis but rather recommend a selective approach, weighing the benefits against the risks. This recommendation is based on the lack of mortality benefit reported in more recent meta-analyses. FQ prophylaxis was demonstrated to reduce bacteremia and febrile neutropenia episodes, although mostly in trials performed in low-resistance settings (<20%), whereas current FQ resistance rates may reach 30-60%. Other disadvantages of FQ include potential adverse events, antibiotic resistance development, cost, increase in Gram-positive infections and resistant Gram-negative infections following prophylaxis, Clostridioides difficile infection, and an effect on gut microbiota.

Key messages: Taking the above into consideration, alternative approaches other than universal FQ prophylaxis should be considered. Centers with high FQ resistance rates may consider either withholding prophylaxis or providing selective prophylaxis for high-risk patients screened negative for FQ-resistant bacteria.

背景氟喹诺酮类药物预防是中性粒细胞减少期间急性白血病(AL)患者常用的治疗方法。这一做法得到了一项较早的荟萃分析的支持,该分析报告称使用FQ预防可以降低死亡率。后来的荟萃分析未能重现这一发现,可能是由于较高的背景FQ耐药率限制了它们的有效性。本文回顾了主要用于AL患者的FQ预防的利弊。大多数现行指南不支持普遍预防,而是推荐一种选择性方法,权衡利弊。这一建议是基于最近的荟萃分析中报告的缺乏死亡率益处。FQ预防被证明可以减少菌血症和发热性中性粒细胞减少发作,尽管主要是在低耐药性环境中进行的试验(
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引用次数: 0
Erratum. 勘误。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2024-02-27 DOI: 10.1159/000537722
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引用次数: 0
Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation. 供体淋巴细胞输注是提高异基因干细胞移植后复发的急性髓细胞白血病和骨髓增生异常综合征患者生存率的可行方法。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-10-12 DOI: 10.1159/000534315
Lia Minculescu, Joanne Reekie, Soeren Lykke Petersen, Brian Thomas Kornblit, Ida Schjoedt, Niels Smedegaard Andersen, Lisbeth Pernille Andersen, Anne Fischer-Nielsen, Eva Kannik Haastrup, Lone Smidstrup Friis, Henrik Sengelov

Introduction: Donor lymphocyte infusion (DLI) is used to induce remission in patients who relapse after allogeneic stem cell transplantation (allo-HSCT). During the last decade, the hypomethylating agent Azacitidine has been used together with DLI for a synergistic graft-versus-leukemia (GVL) effect. Here, we report results of DLI/Azacitidine treatment from a retrospective single-center study.

Methods: Fifty AML/MDS patients treated for relapse after allo-HSCT between 2001 and 2020 with DLI at the Department of Hematology, at Rigshospitalet, Copenhagen University Hospital were included for analyses. A subgroup of patients who obtained complete remission (CR) after reinduction chemotherapy, received DLI in combination with low-dose (32 mg/m2) Azacitidine.

Results: Overall survival in all patients after DLI treatment was 59% at 2 years and 20% at 5 years. Relapse-free survival in patients in CR prior to DLI was 32% after 2 years and 7% after 5 years. In the DLI + low-dose-Azacitidine group, 5-year relapse-free survival was 40%.

Conclusion: DLI remains an effective treatment in post-transplant relapse leaving one-fifth of patients' long-term survivors. Our results support the concomitant use of low-dose Azacitidine in the future use of DLI in order to enhance the GVL effect of donor lymphocytes.

引言:供体淋巴细胞输注(DLI)用于诱导异基因干细胞移植(allo-HSCT)后复发的患者病情缓解。在过去的十年中,低甲基化剂阿扎胞苷与DLI一起用于协同移植物抗白血病(GVL)效果。在此,我们报告了DLI/阿扎胞苷治疗的一项回顾性单中心研究结果。方法:纳入哥本哈根大学医院Rigshospitalet血液科2001年至2020年间接受异基因造血干细胞移植后复发DLI治疗的50名AML/MDS患者进行分析。一组患者在再次诱导化疗后获得完全缓解(CR),接受DLI联合低剂量(32 mg/m2)阿扎胞苷治疗。结果:所有患者在DLI治疗后的总生存率在2年时为59%,在5年时为20%。DLI前CR患者的无复发生存率在2年后为32%,在5年后为7%。DLI+低剂量阿扎胞苷组5年无复发生存率为40%。结论:DLI仍然是治疗移植后复发的有效方法,使五分之一的患者长期存活。我们的研究结果支持在DLI的未来使用中同时使用低剂量阿扎胞苷,以增强供体淋巴细胞的GVL效应。
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引用次数: 0
Frontline Therapy in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的一线治疗。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-10-27 DOI: 10.1159/000534730
Miguel Arguello-Tomas, Nil Albiol, Carol Moreno

Background: The treatment landscape of chronic lymphocytic leukemia (CLL) has tremendously evolved in the last decades, thanks to the introduction of more effective therapies.

Summary: Frontline therapy for patients with CLL includes chemoimmunotherapy (CIT) and pathway inhibitors (PIs) (i.e., bruton tyrosine kinase inhibitors and BCL2 inhibitors); the latter has proved to be more effective than CIT mainly in patients with high-risk features (e.g., TP53 aberrations and unmutated IGHV) with acceptable toxicity. Combinations of PIs are playing the protagonist role as frontline therapy for CLL.

Key messages: In this article, the management of treatment-naïve patients with CLL is discussed.

在过去的几十年里,由于引入了更有效的治疗方法,慢性淋巴细胞白血病(CLL)的治疗格局发生了巨大的变化。CLL患者的一线治疗包括化学免疫疗法(CIT)和通路抑制剂(PI)(即Bruton酪氨酸激酶抑制剂和BCL2抑制剂);后者已被证明比CIT更有效,主要针对具有可接受毒性的高危特征(如TP53畸变、未突变IGHV)的患者。PIs的组合在CLL的一线治疗中扮演着主角的角色。在这篇文章中,讨论了治疗幼稚的CLL患者的管理。
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引用次数: 0
Prognostic Markers in the Era of Targeted Therapies. 靶向治疗时代的预后标志物
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-09-13 DOI: 10.1159/000533704
Sorang Kang, Inhye E Ahn

Background: Small molecules targeting Bruton's tyrosine kinase (BTK) and B-cell lymphoma-2 have become the standard of care for the treatment of chronic lymphocytic leukemia (CLL), replacing chemoimmunotherapy (CIT) in most clinical settings. Ongoing trials explore targeted combinations and minimal residual disease-driven treatment cessation. These dramatic shifts in the current and upcoming treatment landscape of CLL raise the need to reevaluate existing prognostic markers and develop novel ones.

Summary: This review examines prognostic markers in CLL patients treated with standard and investigational targeted therapies. Specifically, initial treatment of TP53 aberrant patients with a BTK inhibitor can achieve 70% progression-free survival (PFS) at 5 years, outperforming the 15% 5-year PFS with a CIT regimen containing fludarabine, cyclophosphamide, and rituximab (FCR). The prognostic implications of the immunoglobulin heavy chain variable gene (IGHV) mutation status have also changed. Unmutated IGHV is associated with inferior PFS and overall survival after FCR and inferior PFS with fixed-duration therapy with venetoclax and anti-CD20 monoclonal antibody but not with continuous BTK inhibitor treatment.

Key messages: (1) Genetic variables (e.g., TP53 aberration, IGHV mutation, complex karyotype) have a prognostic significance in CLL patients treated with targeted therapy. (2) Understanding the prognostic and predictive values of these markers is critical for the development of a risk-adapted treatment strategy in CLL.

背景:靶向布鲁顿酪氨酸激酶(BTK)和B细胞淋巴瘤-2的小分子药物已成为治疗慢性淋巴细胞白血病(CLL)的标准疗法,在大多数临床环境中取代了化学免疫疗法(CIT)。目前正在进行的试验正在探索靶向联合疗法和以最小残留病为导向的停药疗法。摘要:这篇综述探讨了接受标准和研究性靶向疗法治疗的CLL患者的预后指标。具体而言,用BTK抑制剂对TP53畸变患者进行初始治疗可获得70%的5年无进展生存期(PFS),优于用含有氟达拉滨、环磷酰胺和利妥昔单抗(FCR)的CIT方案所获得的15%的5年无进展生存期。免疫球蛋白重链可变基因(IGHV)突变状态对预后的影响也发生了变化。未突变的IGHV与FCR治疗后较差的PFS和总生存期有关,与文尼氯雷和抗CD20单克隆抗体的固定疗程治疗后较差的PFS有关,但与BTK抑制剂的持续治疗无关。(2)了解这些标记物的预后和预测价值对于制定适应CLL风险的治疗策略至关重要。
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引用次数: 0
Exclusion of Acute Myeloid Leukemia Patients with Central Nervous System Involvement from Clinical Trials: An Analysis of the National Institutes of Health Clinical Trials Registry from 2012 to 2022. 将中枢神经系统受累的急性髓细胞白血病患者排除在临床试验之外:2012年至2022年美国国立卫生研究院临床试验注册中心的分析。
IF 1.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-01-01 Epub Date: 2023-09-26 DOI: 10.1159/000533819
Dahniel Sastow, Grace Van Hyfte, Jonathan Feld, Marina Kremyanskaya, John Mascarenhas, Douglas Tremblay

Introduction: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics.

Methods: The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012 and 2022 that were phase 1, 2, or 3 and relevant trial characteristics were extracted.

Results: 1,270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p < 0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p < 0.01). Phase 3 trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase 1 and 2 trials that had higher rates of excluding patients with only active CNS involvement (p < 0.01).

Conclusion: A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active but also with any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials.

引言:急性髓系白血病(AML)的中枢神经系统(CNS)受累可以通过鞘内化疗成功治疗,并具有有争议的预后影响。然而,中枢神经系统受累的患者通常以未知的比率被排除在临床试验之外。我们根据中枢神经系统受累情况系统评估了AML临床试验的排除标准,并确定了与临床试验特征的相关性。方法:检索美国国立卫生研究院临床试验注册中心2012年至2022年期间的I、II或III期成人AML介入试验,并提取相关试验特征。结果:1270项试验被纳入分析,790项试验(62.1%)明确排除中枢神经系统受累。在过去十年中,中枢神经系统排斥率没有显著变化。与仅限于移植人群的试验相比,包括非移植人群的实验中中枢神经系统排除率更高(66.9%对43.8%,P结论:大多数AML临床试验,特别是在非移植环境中,都排除了中枢神经系统受累的患者。其中许多试验,尤其是3期试验,不仅排除了有活动性中枢神经系统病史的患者,而且还排除了有任何中枢神经系统病变史的患者。需要进一步研究来确定对这些患者的最佳管理,以增加在大细胞淋巴瘤中的代表性临床试验。
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引用次数: 0
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