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BackgroundBlinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.Methods and findingsA systematic review was conducted in Pubmed up to December 10, 2021 to retain pediatric clinical trials on blinatumomab. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Four out of the 255 initial references were selected, of which 2 were phase 1/2 clinical trials and 2 phase 3 clinical trials. Blinatumomab was associated with a lower risk of serious adverse events (Risk ratio RR, 0.56; 95% CI, 0.32–0.99), febrile neutropenia (RR, 0.13; 95% CI, 0.06–0.26), infection (RR, 0.40; 95% CI, 0.29–0.56), and grade ≥ 3 adverse events (RR, 0.79; 95% CI, 0.67–0.93) compared to chemotherapy. No difference in the risk of CRS (RR, 8.37; 95% CI, 0.27–260.97) and seizure (RR, 6.43; 95% CI, 0.79–53.08) was observed between groups, while for encephalopathy a higher risk was associated with blinatumomab compared to chemotherapy (RR, 8.90; 95% CI, 1.08–73.29).ConclusionOur data support the good safety profile of bliantumomab in treating pediatric patients with B-ALL.

Poikiloderma with neutropenia (PN) is a very rare genetic disorder mainly characterized by poikiloderma and congenital neutropenia, which explains the recurrence of respiratory infections and risk of developing bronchiectasis. Patients are also prone to develop hematological and skin cancers. Here, we present the case of a patient, the only child of apparently unrelated Serbian parents, affected by PN resulting from the homozygous mutation NM_024598.3:c.243G>A (p.Trp81Ter) of USB1; early onset of poikiloderma (1 year of age) was associated with cutaneous mastocytosis. We also provide a review of the literature on this uncommon condition with a focus on dermatological findings.

BackgroundAmong factors influencing the higher risk of developing unknown or rare adverse drug reactions (ADRs) among children and adolescents, there is the frequent off-label use of drugs that seems to be very common in pediatric oncological patients. Our study aim to collect and evaluate data on the safety profile of antineoplastic drugs and their off-label use in the pediatrics population using real life data.MethodsWe retrieved Individual Case Safety Reports (ICSRs) with an anticancer agent as suspected drug among those reported through the Campania spontaneous reporting system from 1 January 2013 to 30 September 2019. We classified ICSRs into four off-label categories: “age,” “route of administration,” “weight,” and “therapeutic indication.” We defined an ICSR as an off-label case if it met at least one of the aforementioned categories for at least one of the reported suspected antineoplastic drugs.ResultsA total of 18 ICSRs (7.6%) out of 236 were classified as off-label cases. The median age of patients was 13 years (interquartile range, IQR: 6–16), with 94.4% of cases occurring in male patients. In the classification of the off-label category, 16 ICSRs were categorized according to the “therapeutic indication” and two for the “age.” No case was categorized for the off-label categories “route of administration” and “weight.” The two off-label cases categorized as “age” were both related to the use of brentuximab vedotin for Hodgkin’s lymphoma in patients aged 16 years. Twenty-nine ADRs (1.6 suspected adverse drug reactions per ICSR) were identified among off-label cases. Among ADRs, those reported more than one were diarrhea (N = 3), neutropenia (N = 3), nausea (N = 2), pyrexia (N = 2), and vomit (N = 2).ConclusionsOur findings showed a low number of ICSRs classified as off-label. The majority of off-label ICSRs were categorized for the “therapeutic indication.” This low number of off-label ICSRs might be largely due to the underreporting phenomenon, which is a major limit in pharmacovigilance. Therefore, we believe that spreading pharmacovigilance knowledge and awareness might improve this aspect.