Summary Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two‐day Pan‐European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus‐based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes.

The findings suggest that in SCD (1): High steady-state expression of alphaMbeta2 integrin and l-selectin by leukocytes predisposes to severe manifestations. (2) Increased leukocyte AM expression above steady-state levels could be important in the genesis of crisis. (3) The early symptomatic improvement that follows hydroxyurea therapy is mediated via mechanisms independent of increased HbF, and may involve reduced AM expression in leukocytes. (4) Other treatment modalities that reduce leukocyte AM expression might also confer clinical benefit.

SummaryWe previously reported that daily dose pomalidomide (CC-4047), a thalidomide analogue, has excellent anti-myeloma activity but is associated with myelosuppression and deep vein thrombosis. We report here a phase 1 study to determine the maximum tolerated dose (MTD) of pomalidomide at 1 mg, 2 mg, 5 mg and 10 mg on alternate days (ad). Twenty patients with relapsed myeloma were treated. Grade 4 neutropenia occurred in all patients receiving 10 mg and the MTD was defined as 5 mg ad. No thrombotic events were observed. Pomalidomide was continued following the 4-week MTD study in 17/20 patients for a median of 14 months. 10% of patients had a complete response and >50% reduction in paraprotein was achieved in 50% of subjects. Progression-free survival was 10AE5 months and median overall survival was 33 months. A significant rise was observed in the proportion of CD8 + cells. Alternate day pomalidomide was associated with a marked reduction in the incidence of thrombosis whilst maintaining excellent anti-myeloma activity. This trial provides further in vivo evidence that pomalidomide modulates the immune system in myeloma patients. Phase 2 studies to further assess the optimal schedule of administration and anti-myeloma activity of this agent are planned.

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Summary Increasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion and electrospray triple quadrupole mass spectrometry–mass spectrometry (MSMS) in multiple reaction monitoring acquisition mode for the identification of the clinically important haemoglobin variants, S, C, DPunjab, OArab, and E. A total of 200 blood samples, comprising 52 haemoglobin AA, 57 AS (sickle cell trait), 44 AC (C trait), 16 SC (SC disease), 14 SS (sickle cell disease), 10 AE (E trait), 2 ADPunjab (DPunjab trait) and 1 each of AOArab (OArab trait), CC (C disease), DPunjabDPunjab (DPunjab disease), OArabOArab (OArab disease), and EE (E disease), have been analysed in parallel with existing phenotype and molecular methods. All haemoglobin variants were correctly identified by MSMS, with no false positives or false negatives. The system detects both heterozygotes and homozygotes and has potential applications in neonatal and antenatal screening.

Background Sickle cell disease (SCD) is a recognized cause of childhood mortality. Tanzania has the fifth highest incidence of SCD (with an estimated 11 000 SCD annual births) worldwide. Although newborn screening (NBS) for SCD and comprehensive healthcare have been shown to reduce under-5 mortality by up to 94% in high-income countries such as the USA, no country in Africa has maintained NBS for SCD as a national health program. The aims of this program were to establish and evaluate NBS-SCD as a health intervention in Tanzania and to determine the birth prevalence of SCD. Methods Muhimbili University of Health and Allied Sciences conducted NBS for SCD from January 2015 to November 2016. Dried blood spot samples were collected and tested for SCD using isoelectric focusing. Results Screening was conducted on 3981 newborns. Thirty-one (0.8%) babies had SCD, 505 (12.6%) had sickle cell trait and 26 (0.7%) had other hemoglobinopathies. Twenty-eight (90.3%) of the 31 newborns with SCD were enrolled for comprehensive healthcare. Conclusions This is the first report on NBS as a health program for SCD in Tanzania. The SCD birth prevalence of 8 per 1000 births is of public health significance. It is therefore important to conduct NBS for SCD with enrollment into a comprehensive care program.

SummarySerum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and a-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA] n and HMOX1 [GT] n promoter polymorphisms and a globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/b 0 , 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P < 0AE0001 and P < 0AE01, respectively). While HMOX1 genotype had no effect, co-inheritance of a-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD.