Clonal Immunoglobulin DNA and Lymphoma Diagnosis

克隆免疫球蛋白 DNA 和淋巴瘤诊断

• 批准号: 9927306
• 负责人: RICHARD Frederick AMBINDER
• 金额: $ 17.51万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-13 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927306
• 关键词: AIDS-Related Lymphoma; B Cell Proliferation; B-Cell Lymphomas; Biological Assay; Biopsy; Body Weight decreased; Cancer Diagnostics; Cause of Death; Characteristics; Clinical; Clinics and Hospitals; Consumption; Cytology; DNA; Data Analyses; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disease-Free Survival; Educational Activities; Excision biopsy; Failure; Fever; Fine needle aspiration biopsy; Flow Cytometry; Future; Gene Rearrangement; Genetic Markers; Goals; HIV; HIV Infections; Hyperplasia; Immunoglobulins; Incidence; Infrastructure; Investigation; Laboratories; Laboratory Procedures; Letters; Lymphatic Diseases; Lymphoma; Malignant Neoplasms; Medical; Molecular; Molecular Analysis; Morphology; Night Sweating; Nucleic Acids; Opportunistic Infections; Palpable; Pathology; Patient Triage; Patients; Performance Status; Peripheral; Plasma; Predictive Value; Process; Prospective Studies; Quality Control; Resources; Sensitivity and Specificity; Signs and Symptoms; Site; South Africa; South African; Specimen; Specimen Handling; Stretching; Suggestion; Symptoms; Techniques; Technology; Therapeutic procedure; Thinness; Time; Training Activity; Translating; Tuberculosis; Universities; Visit; chemotherapy; co-infection; experience; follow-up; improved; insight; lectures; low and middle-income countries; lymph nodes; molecular marker; next generation sequencing; rapid diagnosis; tuberculosis treatment; tumor DNA

Project Summary Aggressive lymphomas associated with HIV infection are often curable with chemotherapy. Chemotherapy failures are much more common in patients with poor performance status, which manifests as advanced stage disease and is typically associated with a delayed diagnosis. The diagnosis of lymphoma in HIV patients is particularly challenging, and often delayed, because the signs and symptoms of lymphadenopathy, fever, night sweats, and weight loss characteristic of lymphoma may also reflect HIV, or opportunistic infections such as tuberculosis (TB). In South Africa, the diagnosis of lymphoma is especially difficult because of the high incidence of TB co-infection, which is the major cause of death in HIV patients. Fine needle aspiration (FNA) is often performed on palpable and enlarged lymph nodes as a front-line diagnostic procedure. The FNA is sometimes suggestive of lymphoma or TB, and is sometimes indeterminate or non-diagnostic. Lymphadenopathy in this setting is so common, and the medical infrastructure to support excisional biopsy and pathology stretched so thin, that definitive excisional biopsies must be prioritized. Those with FNA findings suspicious for lymphoma are sent for excisional biopsy, while others are treated empirically for TB, and only proceed to biopsy if lymphadenopathy is persistent or progressive despite TB treatment. We propose an investigation of molecular markers that may serve as diagnostic adjuncts to improve prioritization for excisional biopsy. The approach involves molecular analysis of immunoglobulin DNA to detect clonal rearrangements in FNA or in plasma specimens. Several studies suggest that circulating tumor DNA can be detected in the plasma of >95% of patients with aggressive B cell lymphomas. We suspect that these rearrangements would also be frequently detected in FNA as well. We propose to study FNA and plasma specimens from 300 HIV patients with lymphadenopathy undergoing FNA for standard clinical indications at the University of the Witwatersrand-affiliated hospitals and clinics in Johannesburg, South Africa. From this group of patients we will identify at least 30 patients with definitive lymphoma (diagnosed by excisional biopsy) and 30 without lymphoma. To make these clinical determinations (lymphoma vs. no-lymphoma), we will follow patients for up to 6 months while standard diagnostic and therapeutic procedures are pursued. When 30 true positive, and corresponding true negative, cases have been identified, we will determine whether clonal immunoglobulin (cIg) DNA is present in FNA, plasma, or both in order to estimate the sensitivity, specificity, positive predictive value and negative predictive value of cIg DNA as a diagnostic adjunct. These studies will also give insight into clonal B-cell proliferations associated with HIV and coinfections. Positive findings from this preliminary study will set the groundwork for a real-time prospective study to determine whether more rapid diagnosis can improve the performance status and long-term disease- free survival of patients with HIV lymphoma.

项目摘要 与HIV感染相关的侵袭性淋巴瘤通常可以通过化学疗法治愈。 在表现状况较差的患者中，化学疗法失败更为普遍，这表现为 晚期疾病，通常与诊断延迟有关。 HIV中淋巴瘤的诊断 患者特别具有挑战性，并且经常延迟，因为淋巴结肿大的体征和症状， 淋巴瘤的发烧，汗水和减肥特征也可能反映艾滋病毒或机会性感染 例如结核病（TB）。在南非，淋巴瘤的诊断特别困难 结核病感染的发生率，这是HIV患者死亡的主要原因。细针吸入（FNA）为 通常以明显和扩大的淋巴结作为前线诊断程序进行。 FNA是 有时暗示淋巴瘤或结核病，有时是不确定的或非诊断的。 在这种情况下的淋巴结肿大是如此普遍，并且医疗基础设施支持移动活检和 病理延伸得如此薄，以至于必须优先考虑确定的弹性活检。那些有FNA发现的人 可疑对淋巴瘤进行切除活检，而其他人则以经验治疗结核病，只有 如果结核病治疗，淋巴结瘤是持续或进行的，请继续进行活检。我们提出了一个 研究可以用作诊断辅助的分子标记物，以改善省分解的优先次序 活检。该方法涉及对免疫球蛋白DNA的分子分析，以检测克隆重排 FNA或血浆标本中。几项研究表明，可以在血浆中检测到循环肿瘤DNA > 95％的侵袭性B细胞淋巴瘤患者中有95％。我们怀疑这些重排也将是 也经常在FNA中检测到。 我们建议研究300名HIV患者的FNA和血浆标本 在Witwatersrand附属医院和 南非约翰内斯堡的诊所。从这组患者中，我们将发现至少30名患者 明确的淋巴瘤（通过切除活检诊断）和30例无淋巴瘤。使这些临床 确定（淋巴瘤与无淋巴瘤），我们将关注患者长达6个月，而标准诊断 并采用了治疗程序。当30个真正的正面和相应的真实负面的情况时，案件具有 已确定，我们将确定克隆免疫球蛋白（CIG）DNA是否存在于FNA，等离子体或同时 为了估计CIG DNA的灵敏度，特异性，正预测值和负预测值 作为诊断辅助手段。这些研究还将深入了解与HIV相关的克隆B细胞增殖 和共同感染。这项初步研究的积极发现将为实时前瞻性奠定基础 研究以确定更快的诊断是否可以改善性能状况和长期疾病 - HIV淋巴瘤患者的自由存活。