Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.

Late effects and survival of children with malignant solid tumours in northern Finland: a single-centre cohort study.

The global survival rates for childhood cancers are high: approximately 80% of affected children will survive. Nevertheless, the burden of treatment for survivors is also high as three-quarters experience late effects of varying severity following cancer treatment. The aims of this study were to evaluate the treatment-related late effects of patients with childhood solid tumour in northern Finland and to report their survival rates. Our study included 104 patients treated for malignant solid tumours, excluding central nervous system tumours and lymphomas, between 1990 and 2015. Information regarding the type of late effects as well as other clinical data were obtained from the patients' medical records. Late effects were observed in 65 (63%) patients, and almost half (40%) of the patients displayed more than one late effect. The most common late effect was hearing loss (n = 20). The 5-year survival rate in our study was 75%.   Conclusion: Our results highlight the importance of long-term follow-up for childhood cancer survivors. As survivors age and survival rates improve, late effects and their impact on patient health as well as the value of surveillance must be considered. What is Known: • Up to three-quarters of childhood cancer survivors experience treatment-related late effects. What is New: • The 5-year survival rate and the prevalence of late effects amongst childhood solid tumour patients treated in northern Finland are in line with findings from previous studies.

[Transient hemorrhagic diathesis caused by prothrombin-binding antiphospholipid antibody in a child]. / Protrombiiniin sitoutuvan fosfolipidivasta- aineen aiheuttama lapsen ohimenevä verenvuototaipumus.

We describe three previously healthy children who developed acute extensive bruises about two weeks after a mild stomach bug. Coagulation tests revealed a shortened thromboplastin time (TT), long PT time, low level of coagulation factor II, and positive lupus anticoagulant among the antiphospholipid antibodies. In one patient the clinical symptoms disappeared during a one-week course of prednisolone, another one received a prothrombin complex preparation as substitution therapy. In the third patient the symptoms were milder and vanished without any specific treatment. The levels of coagulation factor increased in all patients and the lupus anticoagulant disappeared within a couple of months.

Cytokine responses in cord blood predict the severity of later respiratory syncytial virus infection.

BACKGROUND: It has been claimed that an early respiratory syncytial virus (RSV) infection can induce asthma and recurrent wheezing. OBJECTIVE: We addressed the question of whether infants contracting an early RSV infection differ from healthy children in their cytokine production at birth. METHODS: In a prospective cohort study cord blood samples were collected from 1084 newborns during autumn 2001. Of 47 of these newborns with subsequent virologically confirmed RSV infection before 6 months of age, 24 had enough cells for stimulation in cord blood samples (14 of those were hospitalized). Twenty-eight children had other respiratory virus infections (16 with enough cells), and samples from 48 healthy children of the 1084 total served as control specimens. Stimulated cytokine production of mononuclear cells was measured. The responses in the groups were evaluated by means of factor analysis. RESULTS: The infants hospitalized for RSV infection had higher LPS-stimulated combined IL-6 and IL-8 responses than the infants treated as outpatients (P = .005) or the healthy control subjects (P = .02). The hospitalized patients with RSV showed lower IL-1beta, IL-2, IL-4, IL-5, and IL-10 responses than those treated as outpatients (P = .02). High IL-6 and IL-8 responsiveness predicted a severe RSV infection (odds ratio, 2.20; 95% CI, 1.17-4.14; P = .01). The unstimulated cytokine responses at birth did not differ between the patients and healthy control subjects. CONCLUSION: The results suggest that natural differences in innate immunity predispose children to severe RSV infection rather than the infection modifying immune responses in childhood.

Consumption of asthma medication after RS-virus epidemic--a population based survey.

It has been suggested that a respiratory syncytial virus (RSV) infection in infancy increases the likelihood of development of asthma in childhood. The RSV epidemics have a special 2-yr pattern in Finland and this allows the evaluation of the association of RSV and asthma by epidemiological means. We evaluated whether being 0-6 months of age during an RSV epidemic has an impact on the use of asthma medication later in the childhood. The consumption of asthma medication at the age of 3-16 yr and the number of those entitled to special reimbursement for asthma medication were identified for a total of 637,922 children. These subjects were grouped in cohorts according to whether they had been aged 0-6 months (exposed) or not (unexposed) during an RSV epidemic. The means of the proportions taking asthma medication and of those receiving reimbursement were calculated for each cohort. The means of the proportions in the unexposed vs. exposed cohorts were 20.5% vs. 20.3% for consumption and 4.8% vs. 4.9% for reimbursement. These differences were insignificant. In conclusion exposure to a RSV epidemic in infancy does not increase the consumption of asthma medicines at the population level.