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

• 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
• 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; 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

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：建立一个针对与HIV相关儿童的临床改进平台 撒哈拉以南非洲的恶性肿瘤 撒哈拉以南非洲（SSA）的癌症儿童的结局不可接受，不到20％ 那些被诊断出来的人。相比之下，美国超过85％的癌症儿童幸存。艾滋病毒 流行病使SSA小儿恶性肿瘤的景观复杂化。在SSA中，有一个强调 HIV感染与Kaposi肉瘤（KS）之间的关联，儿童发病率增加了40倍 在乌干达。尽管不太明显，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。艾滋病毒不仅影响了癌症的频率 SSA，与艾滋病毒未感染的同时代人相比，患有艾滋病毒的儿童的结局较差。过去 十五年，已经有一致的努力使SSA的艾滋病毒感染儿童与 抗逆转录病毒疗法（ART）。与SSA合作者合作，全球希望旨在为基础奠定基础 用于国际协作临床试验网络：儿科艾滋病毒/艾滋病与感染有关的恶性肿瘤 撒哈拉以南非洲（PARCA）的研究联盟。 SSA中面临的核心问题是重要的 儿童与艾滋病毒相关的恶性肿瘤的负担和这些患者的存活不良。总体目标 该项目是建立标准化的多站点策略，以提供安全有效的特定疾病和 SSA中KS和MB-NHL儿童的风险分层护理。我们计划通过以下 具体目的： 目标1：评估当前的做法和在PARCA网站上接受癌症治疗的儿童的结果以识别 并解决实施标准化治疗方案的障碍。我们将进行评估 针对患有HIV相关和HIV阴性KS和MB-NHL儿童的SSA临床实践 在风险分层，治疗和支持护理方面。基于这些结果，我们将确定和解决 实施标准化方案的差距。 目标2：确定针对小儿KS实施标准化治疗方案的可行性 MB-NHL跨Parca网站。我们将测试实施标准化的，循证的，风险的可行性 - 乌干达和马拉维的HIV相关和HIV阴性KS和MB-NHL的分层治疗方案。 这种方法的可行性将通过评估风险分层的准确性，完成 规定的方案，毒性，治疗放弃以及一年的无事件和整体生存。 目标3：研究与儿童临床结果相关的临床和生物学特征 在标准化的PARCA治疗方案中处理KS和MB-NHL。为了识别临床和 可能为未来风险分层策略提供依据的生物学因素，我们将评估 基线分期方法，艾滋病毒状况，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。