The benefits and risks of bacille Calmette-Guérin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID) incidence, above which BCG is associated with greater risk than benefit. METHODS: A Markov model was developed to simulate the natural histories of tuberculosis (TB) and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI) and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs). RESULTS: In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations) which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000. CONCLUSION: The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control – including early detection and treatment of infection – may be a safer, more effective alternative

Guidelines for the investigation and management of Transient Leukaemia of Down Syndrome

Methodology This guideline was compiled according to the British Society for Haematology (BSH) process at (http://www.bcshguidelines.com). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Literature review details Ovid MEDLINE and Ovid EMBASE were searched systematically for publications in English from 1980 to the end of 2015 using the key words Transient Abnormal Myelopoiesis, Transient Myeloproliferative Disorder, Transient Leukaemia, and Down Syndrome. Specific searches relating to fetal disease and hepatic parameters were also performed. References from relevant publications were also searched. Working group membership The guideline group was selected to be representative of UK‐based medical experts with invited representatives from the British Association of Perinatal Medicine and the Royal College of Paediatrics and Child Health. Review Review of the manuscript was performed by the BSH Guidelines General Haematology Task Force, the BSH Guidelines Committee and the General Haematology sounding board of BSH. It was also placed on the members section of the BSH website for comment. Further comments were invited from a sounding board of the Childhood Leukaemia Clinicians'27 Network, the Childhood Cancer and Leukaemia Group (CCLG), the Royal College of Paediatrics and Child Health, the British Association of Perinatal Medicine (BAPM) and patient representatives identified through the Down Syndrome Association; these organisations do not necessarily approve or endorse the contents. The objective of this guideline is to provide healthcare professionals with guidance on the investigation and management of patients with Transient Leukaemia of Down Syndrome (TL‐DS). Individual patient circumstances may dictate an alternative approach. This is the first BSH guideline on this topic and is in date at time of publication. Any updates will be posted on the BSH Guidelines website (http://www.bcshguidelines.com).</p

Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia

Phytosterolaemia (sitosterolaemia) is a recessively inherited metabolic condition in which the absorption of both cholesterol and plant-derived cholesterol-like molecules at the gut is unselective and unrestricted. In haematology, Mediterranean stomatocytosis or Mediterranean macrothrombocytopenia is a poorly understood haematological condition that combines stomatocytic haemolysis with the presence of very large platelets. Five pedigrees showing this haematology were identified. Gas chromatography mass spectrometry (GC-MS) showed that all of the patients with this highly specific haematology had grossly elevated levels of phytosterols in the blood, diagnostic of phytosterolaemia. All showed mutations in the ABCG5 and ABCG8 previously linked to phytosterolaemia. Three pedigrees showed five new mutations, while two pedigrees showed the common W361X mutation in ABCG8. We draw the following four conclusions: (i) that Mediterranean stomatocytosis/macrothrombocytopenia is caused by an excess of phytosterols in the blood; (ii) that phytosterolaemia, which does not respond to standard statin treatment, can be diagnosed via the distinctive haematology described here, even when the cholesterol is normal; (iii) that phytosterolaemia should be considered in the differential diagnosis of all patients with large platelets; and (iv) that the platelet size should be noted in patients with hypercholesterolaemia