Mycophenolate mofetil for the treatment of children with immune thrombocytopenia and Evans syndrome. A retrospective data review from the Italian association of paediatric haematology/oncology.

Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments.

Pediatric unit spending in the North of Italy during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, accesses to pediatric health care services decreased, as well as the consumption of traditional drugs, while the median cost per patient at the emergency department slightly increased and the cost of pediatric COVID-19 admissions to the pediatric ward too. Overall spending of a secondary level Pediatric Unit in the last two years has not been previously reported. METHODS: This is a retrospective study conducted by the Pediatric Unit of S. Chiara Hospital of Trento, North of Italy. We collected data on consumption and spending before and during the COVID-19 pandemic (between January 2018 and December 2022). RESULTS: The total spending ranged from 2.141.220 to 2.483.931 euros between 2018 and 2022. COVID-19 spending accounted only for 5-8% of the overall budget, while two macro-areas of spending were identified: (i) biologic drugs for inherited metabolic diseases (IMDs), that impacted for 35.4-41.3%, and (ii) technology devices for type 1 diabetes (T1D), that accounted for 41.6-32.8% of the overall budget, in 2021 and 2022, respectively. Analysis of costs along with the different health care services revealed that: (i) the spending for COVID-19 antigen tests and personal protective equipment had a major impact on the Emergency room budget (from 54 to 68% in the two years); (ii) biological drugs accounted mainly on the Pediatric Ward (for 57%), Day Hospital (for 74%) and rare disease center budget (for 95% of the spending); (iii) the cost for T1D devices was mainly due to continuous glucose monitoring, and impacted for the 97% of the outpatient clinic budget. CONCLUSIONS: The main impact on the budget was not due to COVID-19 pandemic related costs, but to the costs for biologic drugs and T1D devices. Therefore, cost savings could be mainly achieved through generic and biosimilars introduction and with inter-regionals calls for technology devices. We emphasize how the control of spending in pediatric hospital care has probably moved from the bedside (savings on traditional drugs as antibiotics) to the bench of national or inter-regional round tables, to obtain discounts on the costs of biologic drugs and medical devices. Here we provide for the first-time in literature, data for bench-marking between secondary level Pediatric Units before and during the COVID-19 pandemic.

Consensus on COVID-19 Vaccination in Pediatric Oncohematological Patients, on Behalf of Infectious Working Group of Italian Association of Pediatric Hematology Oncology.

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS-CoV-2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS-CoV-2 infection and disease (COVID-19) in the pediatric subjects; COVID-19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID-19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. A high grade of Consensus was obtained on topics such as the potential risk of severe COVID-19 outcome in pediatric oncohematological patients, the need for vaccination as a preventative measure, the type, schedule and booster dose of vaccine, the eligibility of the patients for vaccination, and the timing, definition, and management of contraindications and serious adverse events, and other general prevention measures. All 21 of the statements were approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID-19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays.

Association of Immune Thrombocytopenia and Inflammatory Bowel Disease in Children.

BACKGROUND: The association between inflammatory bowel disease (IBD) and immune thrombocytopenia (ITP) is still uncertain. In this multicenter retrospective study, the coexistence of both diseases was investigated in children diagnosed from 1 January 2000 to 31 December 2019. METHODS: Clinical characteristics of both IBD and ITP, onset of disorders, and patient's response to treatment were collected through a structured form sent to 55 Italian pediatric referring centers for hematological disorders. RESULT: Centers responded to the survey and reported the coexistence of IBD and ITP in 14 children. The first diagnosis was ITP in 57.1% and IBD in 35.7% of patients: it was simultaneous in 7.1%. IBD was classified as ulcerative colitis (57.1%), Crohn disease (35.7%), and unclassified (7.1%). No therapy for IBD other than steroids had any effect on ITP course. Colectomy resulted in recovery from ITP in 1 of the 2 patients surgically treated. ITP was always mild but turned to be chronic in half of patients. CONCLUSIONS: In all patients, ITP was mild without any evident impact on IBD severity, but the incidence of chronic ITP seems to be higher than what is usually observed in the pediatric age group. Colectomy had unpredictable effects on ITP.

Efficacy of mycophenolate on lung disease and autoimmunity in children with immunodeficiency.

The autoimmune manifestations of primary immunodeficiencies, such as autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID), often constitute a great therapeutic challenge and have a significant impact on patients' morbidity and mortality. The most common autoimmune presentations are autoimmune cytopenias, but organ-related autoimmunity is also frequently observed. From a pulmonology perspective, granulomatous/lymphocytic interstitial lung disease (GLILD) is a severe immunological complication which significantly worsens the clinical outcome of these patients and for which there are currently few guidelines or protocols for treatment. We present three cases where the use of Mycophenolate in the context of autoimmune cytopenias proved beneficial also on the lung disease.