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: 10427347
• 负责人: CARL E ALLEN
• 金额: $ 14.97万
• 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/10427347
• 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; implementation barriers; improved; improved outcome; infection related cancer; multidisciplinary; novel strategies; pediatric human immunodeficiency virus; predicting response; programs; response; risk stratification; standardized care; survival outcome; treatment response; 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.

项目三：建立艾滋病相关儿童临床改善平台