Pediatric cancer patients vaccinated against SARS-CoV-2-a clinical and laboratory follow-up.

BACKGROUND: Vaccination against SARS-CoV-2 is recommended for cancer patients. However, long-term data on the effectiveness in the pediatric setting are lacking. METHODS: Pediatric patients < 18 years on active treatment for cancer and without prior SARS-CoV-2 infection received three doses of an mRNA vaccine. The clinical course and humoral and cellular immunity were evaluated at the end of the follow-up period of ≥ 1 year after the third dose of vaccine. RESULTS: SARS-CoV-2 infection occurred in 17 of 19 analyzed patients (median age 16.5 years) during the follow-up period (median 17 months), but no severe symptoms were seen. At ≥ 1 year after the last SARS-CoV-2 antigen exposure, 4 of 17 patients had received the recommended booster vaccine. At the end of the follow-up period, all evaluable 15 patients had anti-SARS-CoV-2 receptor-binding domain IgG antibodies. Twelve of the 15 patients had neutralizing antibody titers ≥ 1:10 against the Delta variant and 12/15 and 13/15 against the BA.1 and BA.5 variants, respectively. Specific T cells against SARS-CoV-2 antigens were seen in 9/13 patients. CONCLUSIONS: Most SARS-CoV-2-vaccinated pediatric cancer patients had SARS-CoV-2 infections and limited interest in booster vaccination. At 1 year after the last antigen exposure, which was mostly an infection, humoral immune responses remained strong. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025254, May 26, 2021.

Committed Lone Fighters And Group Experiences: An International Survey On Pediatric Hematology And Oncology Training In German-Speaking Countries.

INTRODUCTION: In German-speaking countries children with cancer are treated in about 70 hospitals. While national and European curricula for pediatric oncology and hematology (POH) have been developed, little is known, how far these curricula have been implemented into daily training and what topics are deemed urgent by instructors. METHODS AND MATERIALS: In 2022 the Didactics and Educational working party of the German Pediatric Hematology/Oncology Society conducted a survey plus interview by phone call on local educational conditions in POH and needs of educators. RESULTS: Thirty-two (45%) POH centers answered the questionary, half have appointed persons overseeing the training. A wide range educational scenarios were described in some centers. Trainees identified urgent needs in areas such as hybrid education and demanded training workshops on specific topics and intensified networking and a general curriculum implemented into daily care as mandatory. CONCLUSION: This is the first survey on educational issues in POH in German speaking centers, describing the current situation before and under pandemic conditions. Great individual efforts have already been achieved by dedicated teachers. A comprehensive training program in POH is still missing, which translates the national curriculum into daily practice, while improving networking and balancing the resources of the individual centers.

Longitudinal Immune Response to 3 Doses of Messenger RNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Pediatric Patients Receiving Chemotherapy for Cancer.

Our study in 21 pediatric cancer patients demonstrates that 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccine (BioNTech/Pfizer) elicited both humoral and cellular immunity in most patients during chemotherapy. Immunity was stronger in children with solid tumors and during maintenance therapy compared to those with hematological malignancies or during intensive chemotherapy. Clinical Trials Registration.ȃGerman Registry for Clinical Trials (DRKS00025254).

School and kindergarten attendance and home schooling of pediatric cancer patients before and during the SARS-CoV-2 pandemic: results of a survey of the German Society for Pediatric Oncology and Hematology.

In this multicenter survey (July 07 to August 08, 2020) in pediatric oncology centers (POCs) belonging to the German Society for Pediatric Oncology and Hematology (GPOH), 36 POCs participated (response rate 70.6%). Home schooling practice was judged as satisfying by 79% prior to and by 38% during the pandemic (P=0.0007). The individual risk of a SARS-CoV-2 infection and the risk of transmission to other patients/caregivers were arguments against attendance. Most POCs recommended regular social participation/school attendance after the end of intensive therapy. 81% stated that persisting restrictions result in serious negative psychosocial consequences for the patients and their families. In-hospital school education, home schooling and re-attendance of school and kindergarten among pediatric cancer patients have suffered a severe setback during the SARS-CoV-2 pandemic. Continuous communication and education concerning protective measures as well as an individual risk assessment are required to avoid the detrimental exclusion of pediatric oncology patients from kindergarten and school.

Cofactor-independent antiphospholipid antibodies activate the NLRP3-inflammasome via endosomal NADPH-oxidase: implications for the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) is an autoimmune disease characterised by thromboembolic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Here we show that three cofactor independent human monoclonal aPL can induce transcription of NLRP3 and caspase-1 resulting in inflammasome activation specific for NLRP3. This depends fully on activation of endosomal NADPH-oxidase-2 (NOX2) by aPL. Activation of NOX2 and subsequent inflammasome activation by aPL are independent from TLR2 or TLR4. While endosomal superoxide production induces caspase-1 and NLRP3 transcription, it does not affect prae-IL-1ß transcription. Therefore, release of IL-1ß occurs only after activation of additional pathways like TLR7/8 or TLR2. All effects exerted by the monoclonal aPL can be reproduced with IgG fractions of APS patients proving that the monoclonal aPL are representative for the APS. IgG fractions of healthy controls or patients suffering from systemic lupus erythematosus have no effect. In a mouse model of the APS we can show inflammasome activation in vivo. Furthermore, mononuclear cells isolated from patients with the APS show an increased expression of caspase-1 and NLRP3 which is accompanied by a three-fold increased serum concentration of IL-1ß suggesting chronic inflammasome activation in APS patients. In summary, we provide further evidence that endosomal NOX2 can be activated by cofactor independent aPL. This leads to induction of the NLRP3 inflammasome. Our data indicate that cofactor independent aPL might contribute significantly to the pathogenesis of the APS.