Simoctocog alfa (Nuwiq) in children: early steps in life's journey for people with severe hemophilia A.

People with severe hemophilia A usually experience their first bleed early in life. In children with severe hemophilia A, primary prophylaxis is recommended to prevent recurrent and potentially life-threatening bleeds that significantly impact day-to-day life. Factor VIII (FVIII) prophylaxis is well-established in children and has been shown to reduce the development of hemophilic arthropathy.

Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL-class fusion.

Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively.

Characterization and treatment of congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years.

Major bleeding disorders: diagnosis, classification, management and recent developments in haemophilia.

In this review, we outline the standard of care for children in the UK with the most common major bleeding disorder, haemophilia, and how exciting new developments in therapy have the potential for further improvements in quality of life and clinical outcome. The combination of comprehensive specialist medical care, safer factor concentrates, earlier introduction of prophylaxis and patient-specific education has allowed the current generation of patients with haemophilia to grow into adulthood with excellent joint function, pursuing full-time employment with a good quality of life. We are entering an exciting new phase in paediatric haemophilia as potentially life-changing products appear on the scene taking a step towards achieving better, easier and personalised prophylaxis.

Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update.

Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is preceded by a transient neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in the key haematopoietic transcription factor gene GATA1.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT.

We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).

Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells.

HDAC inhibitors (HDACi) increase transcription of some genes through histone hyperacetylation. To test the hypothesis that HDACi-mediated enhanced transcription might be of therapeutic value for inherited enzyme deficiency disorders, we focused on the glycolytic and pentose phosphate pathways (GPPPs). We show that among the 16 genes of the GPPPs, HDACi selectively enhance transcription of glucose 6-phosphate dehydrogenase (G6PD).

GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia.

Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis.

An unusual case of hypereosinophilia and abdominal pain: an outbreak of Trichostrongylus imported from New Zealand.

We report an outbreak of severe symptomatic Trichostrongylus spp. in travelers visiting a sheep farm in New Zealand. The unusual source of the outbreak was traced as the use of sheep manure as an organic fertilizer on a salad garden.

Exhaled nitric oxide after a single dose of intramuscular triamcinolone in children with difficult to control asthma.

In a previous study, we reported that intramuscular (IM) triamcinolone improves symptoms in children with difficult asthma. In 2005, we revised our difficult asthma protocol to include assessment of airway inflammation, both directly using sputum induction and indirectly by measurement of exhaled nitric oxide (eNO). In this retrospective review, we aimed to describe (i) the changes in eNO and symptoms after a single 60 mg dose of IM triamcinolone and (ii) the changes in inflammatory markers in the subgroup with non-eosinophilic asthma (i.