ABSTRACT
CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a dramatic impact on the natural history and survival of patients with high-risk B-cell non-Hodgkin lymphoma. Accompanying this success has been the development of new fields of medicine and investigation into toxicity risks and mitigation therapies, mechanisms of resistance and the development of novel and next generation products and strategies in order to address relapse, and issues related to global access and health care economics. This article is a survey of each of these areas as it pertains to the rapidly evolving field of CAR T-cell therapy, written by an International community of lymphoma experts, who also happen to be women.
ABSTRACT
Background: Paroxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia. Objective: This study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation. Methods: Patients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14. Results: Twenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group. Conclusion: More than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.
ABSTRACT
Background. The admission of children to an intensive care unit (ICU) necessitates the selection of children who will benefit most from scarce ICU resources. Decisions should be based on objective data available on outcomes related to particular conditions and resource availability. Objective. To determine which sociodemographic factors and paediatric scoring systems can be used on admission to identify patients who would derive the most benefit.Methods. A retrospective review was undertaken of the charts of children admitted to a paediatric ICU (PICU) over a 6-month period. Charts were analysed according to health status; biographical and demographic data; as well as Pediatric Risk of Mortality (PRISM); Pediatric Logistic Organ Dysfunction (PELOD) and Paediatric Index of Mortality 3 (PIM3) scores to determine which factors were associated with an increased mortality risk.Results. Two hundred and two children were admitted during the study period. Ninety-six children were included in the study; 79 files were not found and 27 children were ineligible. The median age was 14 months and the mortality rate was 15.6%. The significant factor associated with mortality was severe malnutrition. In total 88% of required data were available for the calculation of both the PRISM and PELOD scores and 95% for PIM3 score. The PRISM; PELOD and PIM3 standardised mortality ratios were 2.5; 4.8 and 2.9; respectively. P-values for PRISM; PELOD and PIM3 were 0.05.Conclusion. Severe malnutrition is a statistically significant factor in predicting mortality. This possibly reflects the social context in which the children live. PRISM; PELOD and PIM3 underpredict mortality in our setting. A larger sample is required to verify these outcomes and to determine whether other factors play a role