Successful treatment of a solitary skull metastasis in a child with Wilms' Tumor

This report presents the successful treatment of a child with a solitary metastatic lesion to the calvarium following treatment for Stage III anaplastic Wilms’ Tumor

A Pilot Study of Circulating Endothelial and Hematopoietic Progenitor Cells in Children With Sarcomas

Utilizing a multiparametric flow cytometry protocol, we assessed various cell types implicated in tumor angiogenesis that were found circulating in the peripheral blood of children with sarcomas (cases) based on their cell surface antigen expression. Circulating endothelial cells (CECs), endothelial colony-forming cells (ECFCs), and the ratio of 2 distinct populations of circulating hematopoietic stem and progenitor cells (CHSPCs), the proangiogenic CHSPCs (pCHSPCs) and nonangiogenic CHSPCs (nCHSPCs) were enumerated. Multiparametric flow cytometry was analyzed in cases at baseline and at 4 additional timepoints until the end of treatment and levels compared with each other and with healthy controls. At all timepoints, cases had significantly lower levels of CECs, but elevated ECFCs and a pCHSPC:nCHSPC ratio compared with controls (all P-values <0.05). There was no significant difference in any of the cell types analyzed based on tumor histology, stage (localized vs. metastatic), or tumor size. After treatment, only the CECs among the complete responders were significantly lower at end of therapy (P<0.01) compared with nonresponders, whereas the ECFCs among all cases significantly increased (P<0.05) compared with baseline. No decline in the pCHSPC:nCHSPC ratio was observed despite tumor response. On the basis of these results, a validation of CECs as prognostic biomarker is now warranted

Building a Sustainable Comprehensive Multiple Myeloma Program in Western Kenya

Despite improved treatment strategies for multiple myeloma (MM), patient outcomes in low- and middle-income countries remain poor, unlike high-income countries. Scarcity of specialized human resources and diagnostic, treatment, and survivorship infrastructure are some of the barriers that patients with MM, clinicians, and policymakers have to overcome in the former setting. To improve outcomes of patients with MM in Western Kenya, the Academic Model Providing Access to Healthcare (AMPATH) MM Program was set up in 2012. In this article, the program's activities, challenges, and future plans are described distilling important lessons that can be replicated in similar settings. Through the program, training on diagnosis and treatment of MM was offered to healthcare professionals from 35 peripheral health facilities across Western Kenya in 2018 and 2019. Access to antimyeloma drugs including novel agents was secured, and pharmacovigilance systems were developed. Finally, patients were supported to obtain health insurance in addition to receiving peer support through participation in support group meetings. This article provides an implementation blueprint for similar initiatives aimed at increasing access to care for patients with MM in underserved areas

Outcomes of Wilms tumor treatment in western Kenya

Background/objectives Wilms tumor (WT) is a curable type of cancer with 5-year survival rates of over 90% in high-income countries, whereas this is less than 50% in low- and middle-income countries. We assessed treatment outcomes of children with WT treated at a large Kenyan teaching and referral hospital. Design/methods We conducted a retrospective record review of children diagnosed with WT between 2013 and 2016. Treatment protocol consisted of 6 weeks of preoperative chemotherapy and surgery, and 4–18 weeks of postoperative chemotherapy depending on disease stage. Probability of event-free survival (pEFS) and overall survival (pOS) was assessed using Kaplan–Meier method with Cox regression analysis. Competing events were analyzed with cumulative incidences and Fine–Gray regression analysis. Results Of the 92 diagnosed patients, 69% presented with high-stage disease. Two-year observed EFS and OS were, respectively, 43.5% and 67%. Twenty-seven percent of children died, 19% abandoned treatment, and 11% suffered from progressive or relapsed disease. Patients who were diagnosed in 2015–2016 compared to 2013–2014 showed higher pEFS. They less often had progressive or relapsed disease (p = .015) and borderline significant less often abandonment of treatment (p = .09). Twenty-nine children received radiotherapy, and 2-year pEFS in this group was 86%. Conclusion Outcome of children with WT improved over the years despite advanced stage at presentation. Survival probabilities of patients receiving comprehensive therapy including radiation are approaching those of patients in high-income countries. Additional improvement could be achieved by ensuring that patients receive all required treatment and working on earlier diagnosis strategies

Retrospective Analysis of Presentation, Treatment, and Outcomes of Multiple Myeloma at a Large Public Referral Hospital in Eldoret, Kenya

Purpose: Treatment patterns and survival outcomes of patients with multiple myeloma (MM) in Kenya have not been adequately characterized. The objectives of this study were to describe the clinical, laboratory, and imaging findings at diagnosis, to describe the treatment offered, and to determine the survival outcomes of patients with MM over an 11-year period. Patients and methods: A retrospective chart review was carried out for all patients who were diagnosed and treated for MM at Moi Teaching and Referral Hospital from 2009 to 2019. The Kaplan-Meier method was used to estimate survival. Factors affecting survival were identified using univariate and multivariate analyses. Results: A total of 221 patient charts were analyzed of which 124 belonged to male patients (56.1%). The median age at diagnosis was 61 years. Bone pain was the most common presenting complaint observed in 69.6% of 194 patients assessed. Out of 102 patients who received imaging studies, 60 (58.8%) had lytic lesions, 30 (29.4%) had fractures, whereas 30 (29.4%) had spinal cord compression. Anemia, renal failure, and hypercalcemia were observed in 87/187 (46.5%), 22/161 (13.7%), and 23/42 (54.8%) patients, respectively. Thalidomide and dexamethasone (65.2%); bortezomib, thalidomide, and dexamethasone (14.6%); and melphalan and prednisolone (11.9%) were the most prescribed initial chemotherapy regimens among 219 patients analyzed. Overall survival at 1 and 5 years was 70% and 21%, respectively; median overall survival was 29.0 months. In multivariate analysis, male sex (hazard ratio [HR] 1.9), baseline anemia (HR 1.8), and baseline renal failure (HR 3.2) were associated with significantly shorter survival. Conclusion: Survival outcomes were poor despite increased use of multiagent-based chemotherapy regimens. Greater access to available diagnostics and treatments is required to achieve rational treatment and increased survival

Optimal management of endemic Burkitt lymphoma: a holistic approach mindful of limited resources

Endemic Burkitt lymphoma (BL) was publically described in 1958 and remains the most prevalent pediatric cancer in equatorial Africa with an annual incidence between two and five cases per 100,000 children. Several risk factors have been identified, including early-age infection with Epstein–Barr virus, a geographic association with high Plasmodium falciparummalaria transmission, and poor nutrition. However, other modifiable factors play a role in the survival of these children. Treatment regimens for BL have evolved over a time period that spans nearly 50 years. This review will compare survival between different combination chemotherapeutic regimens and discuss other key determinants of outcomes among children diagnosed with BL in resource-limited settings. A discussion of obstacles to diagnosis will be presented, including low community awareness of pediatric cancer, limited access to health facilities, inaccurate or delayed diagnosis often beginning at lower level health rural facilities that are typically staffed by those with limited training in oncology, and insufficient pathology support to confirm diagnosis. Other challenges examined here include those related to treatment adherence, specifically the social and economic stressors that can lead to abandonment of care, and treatment-related toxicity, a challenge compounded not only by the scarcity of medications for supportive care, but also the paucity of clinically trained medical professionals available to manage integrated care for these children. Future directions for enhancing BL survival will be discussed including molecular approaches for rational drug discovery as well as the benefits of forming a unified, global BL research network

Optimal chemotherapy for leukemia: a model-based strategy for individualized treatment.

Acute Lymphoblastic Leukemia, commonly known as ALL, is a predominant form of cancer during childhood. With the advent of modern healthcare support, the 5-year survival rate has been impressive in the recent past. However, long-term ALL survivors embattle several treatment-related medical and socio-economic complications due to excessive and inordinate chemotherapy doses received during treatment. In this work, we present a model-based approach to personalize 6-Mercaptopurine (6-MP) treatment for childhood ALL with a provision for incorporating the pharmacogenomic variations among patients. Semi-mechanistic mathematical models were developed and validated for i) 6-MP metabolism, ii) red blood cell mean corpuscular volume (MCV) dynamics, a surrogate marker for treatment efficacy, and iii) leukopenia, a major side-effect. With the constraint of getting limited data from clinics, a global sensitivity analysis based model reduction technique was employed to reduce the parameter space arising from semi-mechanistic models. The reduced, sensitive parameters were used to individualize the average patient model to a specific patient so as to minimize the model uncertainty. Models fit the data well and mimic diverse behavior observed among patients with minimum parameters. The model was validated with real patient data obtained from literature and Riley Hospital for Children in Indianapolis. Patient models were used to optimize the dose for an individual patient through nonlinear model predictive control. The implementation of our approach in clinical practice is realizable with routinely measured complete blood counts (CBC) and a few additional metabolite measurements. The proposed approach promises to achieve model-based individualized treatment to a specific patient, as opposed to a standard-dose-for-all, and to prescribe an optimal dose for a desired outcome with minimum side-effects