Establishing a Platform for Clinical Improvement for Children with HIV-Associated Malignancies in Sub-Saharan Africa

为撒哈拉以南非洲地区患有艾滋病毒相关恶性肿瘤的儿童建立临床改进平台

基本信息

批准号：
10223903
负责人：
CARL E ALLEN
金额：
$ 14.94万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-25 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10223903
关键词：
AIDS related cancer AIDS/HIV problem Acquired Immunodeficiency Syndrome Address Adopted Adoption Affect Africa South of the Sahara Awareness B-Cell NonHodgkins Lymphoma Biologic Characteristic Biology Bone Marrow Botswana Caring Central Africa Cerebrospinal Fluid Child Child Care Childhood Clinical Clinical Research Clinical Treatment Clinical Trials Network Collaborations Complex Conduct Clinical Trials Development Diagnosis Diagnostic Imaging Disease Eastern Africa Epidemic Evaluation Event Foundations Frequencies Future Goals HIV HIV Infections HIV Seronegativity Health Hematology Hospitals Human Herpesvirus 4 Human Herpesvirus 8 Human Resources Incidence Inferior Infrastructure International Kaposi Sarcoma Lactate Dehydrogenase Malawi Malignant Childhood Neoplasm Malignant Neoplasms Malnutrition Mature B-Lymphocyte Medicine Methods Modeling Outcome Pathology Patients Pediatric Hospitals Pediatric Oncology Pediatric Oncology Group Phenotype Plasma Poverty Regimen Research Risk Site Staging Standardization Supportive care Texas Toxic effect Treatment Protocols Tumor Markers Uganda United States antiretroviral therapy base chronic infection clinical care clinical center clinical practice clinically significant college comorbidity cytokine evidence base experience feasibility testing high risk improved improved outcome infection related cancer multidisciplinary novel strategies pediatric human immunodeficiency virus predicting response programs response risk stratification standardized care survival outcome treatment strategy tumor

项目摘要

PROJECT 3: Establishing a Platform for Clinical Improvement for Children with HIV-Associated Malignancies in Sub-Saharan Africa Outcomes for children with cancer in sub-Saharan Africa (SSA) are unacceptably poor, with fewer than 20% of those diagnosed surviving. By contrast, over 85% of children with cancer in the United States survive. The HIV epidemic complicates the landscape of pediatric malignancies in SSA. In SSA, there has been an emphatic association between HIV infection and Kaposi sarcoma (KS), with a 40-fold increase in KS incidence in children in Uganda. And although less pronounced, associations between HIV and mature B cell non-Hodgkin lymphoma (MB-NHL) have been established throughout the region. Not only has HIV impacted the frequency of cancer in SSA, children with HIV have inferior outcomes compared to their HIV-uninfected contemporaries. Over the past fifteen years, there has been a concerted effort to enable treatment of HIV-infected children in SSA with antiretroviral therapy (ART). In partnership with collaborators in SSA, Global HOPE aims to lay the foundation for an international collaborative clinical trial network: Pediatric HIV/AIDS & Infection-Related Malignancies Research Consortium for Sub-Saharan Africa (PARCA). The central problem faced in SSA is the significant burden of HIV-associated malignancies in children and the poor survival of these patients. The overall goal of this project is to establish a standardized multi-site strategy to deliver safe and effective disease-specific and risk-stratified care to children with KS and MB-NHL in SSA. We plan to achieve this goal through the following specific aims: Aim 1: Evaluate current practices and outcomes of children treated for cancer at PARCA sites to identify and address barriers to implementation of standardize treatment regimens. We will perform assessments of current clinical practices in SSA for children with HIV-associated and HIV-negative KS and MB-NHL with focus on risk-stratification, delivery of therapy, and supportive care. Based on these results, we will identify and address gaps in implementation of standardized regimens. Aim 2: Determine the feasibility of implementing standardized treatment regimens for pediatric KS and MB-NHL across PARCA sites. We will test the feasibility of implementing standardized, evidence-based, risk- stratified treatment regimens for HIV-associated and HIV-negative KS and MB-NHL in Uganda and Malawi. Feasibility of this approach will be determined by evaluating accuracy of risk-stratification, completion of prescribed regimen, toxicity, treatment abandonment, and 1-year event-free and overall survival. Aim 3: Investigate clinical and biological characteristics associated with clinical outcomes of children with KS and MB-NHL treated on standardized PARCA treatment regimens. In order to identify clinical and biology factors that may inform future risk-stratification strategies, we will evaluate the clinical significance of baseline staging methods, HIV status, tumor biomarkers and explore potential for plasma cytokines to predict response to therapy.

项目 3：建立 HIV 相关儿童临床改进平台撒哈拉以南非洲的恶性肿瘤撒哈拉以南非洲地区 (SSA) 癌症儿童的治疗结果极其糟糕，不到 20% 那些被诊断存活的人。相比之下，美国超过 85% 的癌症儿童存活下来。艾滋病毒流行病使 SSA 儿童恶性肿瘤的情况变得复杂化。在 SSA 中，有一个强调 HIV 感染与卡波西肉瘤 (KS) 之间的关联，儿童 KS 发病率增加 40 倍在乌干达。虽然不太明显，但 HIV 与成熟 B 细胞非霍奇金淋巴瘤之间的关联 (MB-NHL) 已在整个地区建立。艾滋病毒不仅影响癌症的发病率 SSA，与未感染艾滋病毒的同龄人相比，感染艾滋病毒的儿童的结局较差。过去的事十五年来，我们一直在共同努力，为撒哈拉以南非洲地区感染艾滋病毒的儿童提供治疗抗逆转录病毒治疗（ART）。 Global HOPE 与 SSA 的合作者合作，旨在奠定基础国际合作临床试验网络：儿科艾滋病毒/艾滋病和感染相关恶性肿瘤撒哈拉以南非洲研究联盟 (PARCA)。 SSA 面临的核心问题是儿童艾滋病毒相关恶性肿瘤的负担以及这些患者的生存状况不佳。总体目标为该项目旨在建立标准化的多站点策略，以提供安全有效的针对特定疾病和对 SSA 中 KS 和 MB-NHL 儿童进行风险分层护理。我们计划通过以下方式实现这一目标具体目标：目标 1：评估在 PARCA 站点接受癌症治疗的儿童的当前做法和结果，以确定并解决实施标准化治疗方案的障碍。我们将进行评估当前针对 HIV 相关儿童和 HIV 阴性 KS 和 MB-NHL 儿童的 SSA 临床实践风险分层、治疗实施和支持性护理。根据这些结果，我们将确定并解决标准化治疗方案实施方面的差距。目标 2：确定实施儿童 KS 标准化治疗方案的可行性跨 PARCA 站点的 MB-NHL。我们将测试实施标准化、基于证据、风险的可行性乌干达和马拉维针对 HIV 相关和 HIV 阴性 KS 和 MB-NHL 的分层治疗方案。该方法的可行性将通过评估风险分层的准确性、完成情况来确定处方治疗方案、毒性、治疗放弃以及 1 年无事件生存率和总生存率。目标 3：调查与儿童临床结果相关的临床和生物学特征采用标准化 PARCA 治疗方案治疗 KS 和 MB-NHL。为了识别临床和可能为未来风险分层策略提供信息的生物学因素，我们将评估其临床意义基线分期方法、HIV 状态、肿瘤生物标志物并探索血浆细胞因子预测的潜力对治疗的反应。