Case Report: An unusual case of priapism

No Abstrac

Anti-tumor activity without on-target off-tumor toxicity of GD2-Chimeric Antigen Receptor T cells in patients with neuroblastoma

The reprogramming of a patient’s immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity

The vaccination of 35,000 dogs in 20 working days using combined static point and door-to-door methods in Blantyre, Malawi

An estimated 60,000 people die of rabies annually. The vast majority of cases of human rabies develop following a bite from an infected dog. Rabies can be controlled in both human and canine populations through widespread vaccination of dogs. Rabies is particularly problematic in Malawi, costing the country an estimated 13 million USD and 484 human deaths annually, with an increasing paediatric incidence in Blantyre City. Consequently, the aim of this study was to vaccinate a minimum of 75% of all the dogs within Blantyre city during a one month period. Blantyre's 25 administrative wards were divided into 204 working zones. For initial planning, a mean human:dog ratio from the literature enabled estimation of dog population size and dog surveys were then performed in 29 working zones in order to assess dog distribution by land type. Vaccination was conducted at static point stations at weekends, at a total of 44 sites, with each operating for an average of 1.3 days. On Monday to Wednesday, door-to-door vaccination sessions were undertaken in the areas surrounding the preceding static point stations. 23,442 dogs were vaccinated at static point stations and 11,774 dogs were vaccinated during door-to-door vaccinations. At the end of the 20 day vaccination programme, an assessment of vaccination coverage through door-to-door surveys found that of 10,919 dogs observed, 8,661 were vaccinated resulting in a vaccination coverage of 79.3% (95%CI 78.6-80.1%). The estimated human:dog ratio for Blantyre city was 18.1:1. Mobile technology facilitated the collection of data as well as efficient direction and coordination of vaccination teams in near real time. This study demonstrates the feasibility of vaccinating large numbers of dogs at a high vaccination coverage, over a short time period in a large African city

Kaposi's sarcoma in children: An open randomised trial of vincristine, oral etoposide and a combination of vincristine and bleomycin

Introduction: Kaposi's sarcoma (KS) is a common childhood cancer in places where HIV is endemic and access to antiretroviral therapy (ART) is delayed. Despite this there are no randomised trials to compare and assess chemotherapeutic regimens. Method: An open label, randomised trial comparing intravenous vincristine alone, vincristine and bleomycin and oral etoposide, was carried out in children with Kaposi's sarcoma in the Queen Elizabeth Central Hospital, Blantyre, Malawi. HIV infected children were given ART after 2-3 courses of chemotherapy if they were not already on treatment. Neither HIV nor widespread KS are curable and treatment is aimed at disease reduction and improved quality of life. Tumour reduction was assessed by measuring the size of sentinel KS nodules and quality of life (QoL) by using the Lansky score. Follow up was until death or for one year. Findings: 92 children were enrolled of whom 46% were naive to ART; 10 (11%) were HIV negative. Survival was not influenced by age or gender but was better in the oral etoposide and the vincristine and bleomycin groups. P = 0.0045. The group receiving oral etoposide had a better quality of life. Toxicity was not significant, and any drop in haemoglobin or white cell count could have been causally related to HIV infection rather than cytotoxic therapy. Conclusion: Oral etoposide is a safe, effective treatment to contain KS and improve QoL which can be achieved without many visits to the hospital and intravenous injections. (C) 2014 Elsevier Ltd. All rights reserved