Nephroblastoma Treatment and Outcomes in a Low-Income Setting.

PURPOSE: Nephroblastoma is a highly curable pediatric cancer that requires multidisciplinary care. Few reports have assessed long-term treatment outcomes in low-resource settings using a task-shifting model of care. We report outcomes of a large cohort and factors associated with survival. METHODS: We performed a retrospective chart review of all patients with nephroblastoma presenting to the Butaro Cancer Center of Excellence in Rwanda between July 2012 and June 2018. RESULTS: In total, 136 patients were identified and treated according to International Society of Pediatric Oncology guidelines for low-income settings. Median age at diagnosis was 39.7 months (interquartile range, 25.3-61.8 months); 56.6% were female. Sixty-one (44.9%) patients presented with stage I-III disease, 35 (25.7%) with stage IV disease, and 6 (4.4%) with stage V disease; the remainder were unstaged (n = 34; 25.0%). Most patients completed surgery (n = 97; 71.3%) and postoperative chemotherapy (n = 82; 60.2%); 17 patients received radiotherapy. With a median follow-up time of 18.1 months, 44.9% of patients were alive, 41.9% had died, 8.8% were lost to follow-up, and 4.4% were referred for palliative care or declined further care at the end of the study. Three-year overall survival was 57.5% (95% CI, 48.1 to 65.8) for the entire cohort, and 80.1% (95% CI, 66.8 to 88.5) and 44.0% (95% CI, 26.8 to 60.0) for stages I-III and IV-V, respectively. CONCLUSION: We demonstrate that patients with nephroblastoma can be successfully treated in a low-resource setting. Survival remains lower than in high-income countries, in part due to early deaths, contributing to approximately 30% of patients not being medically able to receive surgical intervention. Next steps include the development of strategies that focus on earlier diagnosis, supportive care during the early phases of therapy, and efficient and timely transitions between specialties for multimodal care.

A Ten-Year Experience of Treating Chronic Myeloid Leukemia in Rural Rwanda: Outcomes and Insights for a Changing Landscape.

PURPOSE: In describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development. METHODS: We retrospectively reviewed all patients with BCR-ABL-positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test. RESULTS: One hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days (P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis (P = .056) and imatinib initiation (P = .170) was not significantly different. CONCLUSION: Coupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria.

BACKGROUND: Our prior study findings suggest that Plasmodium falciparum is the cause of disease in both malaria retinopathy-positive (RP) and most retinopathy-negative (RN) cerebral malaria (CM), and that absence of retinopathy and decreased disease severity in RN CM may be due to shorter duration of illness, lower parasite biomass, and decreased var gene expression in RN compared to RP CM. In the present study, we assessed the pathophysiology of RP and RN CM. METHODS: We compared markers of systemic and central nervous system inflammation, oxidative stress, neuronal injury, systemic endothelial activation, angiogenesis, and platelet activation in Ugandan children with RP (n = 167) or RN (n = 87) CM. RESULTS: RP children had higher plasma C-reactive protein (P = .013), ferritin and erythropoietin (both P < .001) levels, an elevated cerebrospinal fluid (CSF):plasma albumin ratio (P < .001), and higher CSF tau protein levels (P = .049) than RN children. Levels of plasma and CSF proinflammatory and anti-inflammatory cytokines and oxidative stress markers did not differ between RP and RN children. RN children had higher plasma levels of endothelin 1 (P = .003), platelet-derived growth factor (P = .012), and platelet factor 4 (P = .034). CONCLUSIONS: RP and RN CM may represent different phases of CM. RN CM may be driven by early vasospasm and platelet activation, whereas the more advanced RP CM is associated with greater inflammation, increased erythropoietic drive, blood-brain barrier breakdown, and neuronal injury, each of which may contribute to greater disease severity.

Clinical Comparison of Retinopathy-Positive and Retinopathy-Negative Cerebral Malaria.

AbstractCerebral malaria (CM) is a severe and often lethal complication of falciparum malaria. A classic malaria retinopathy is seen in some (retinopathy-positive [RP]) children but not others (retinopathy-negative [RN]), and is associated with increased parasite sequestration. It is unclear whether RN CM is a severe nonmalarial illness with incidental parasitemia or a less severe form of the same malarial illness as RP CM. Understanding the clinical differences between RP and RN CM may help shed light on the pathophysiology of malarial retinopathy. We compared clinical history, physical examination, laboratory findings, and outcomes of RP (N = 167) and RN (N = 87) children admitted to Mulago Hospital, Kampala, Uganda. Compared with RN children, RP children presented with a longer history of illness, as well as physical examination and laboratory findings indicative of more severe disease and organ damage. The hospital course of RP children was complicated by longer coma duration and a greater transfusion burden than RN children. Mortality did not differ significantly between RP and RN children (14.4% versus 8.0%, P = 0.14). Further, severity of retinal hemorrhage correlated with the majority of variables that differed between RP and RN children. The data suggest that RP and RN CM may reflect the spectrum of illness in CM, and that RN CM could be an earlier, less severe form of disease.