Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study.

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these.

Seroprevalence and silent infection rate during SARS-CoV-2 pandemic among children and adolescents in Western Pomerania: a multicenter, cross-sectional study-the COVIDKID study.

Background: Limited data on SARS-CoV-2 seroprevalence in rural areas of northern Germany necessitate comprehensive cohort studies. We aimed to evaluate the seroprevalence, silent infection (SI) rates and risk factors for infections among children and adolescents in Western Pomerania from December 2020 to August 2022.

Methods: In this cross-sectional study, serum or plasma samples from children and adolescents (6 months to 17 years) were collected during routine blood draw.

A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant Leukemia Cells Overexpressing BCL-2.

From previous studies, it is evident that metal-organic gold(I) complexes have antiproliferative activities. The aim of this study is not only to find new anticancer agents but also to overcome existing cytostatic resistance in cancer cells. The synthesis and medicinal evaluation of two cationic 1,3-disubstituted gold(I) bis-tetrazolylidene complexes and are reported.

Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial.

Background: Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan-temozolomide and dasatinib-rapamycin (RIST) in patients with relapsed or refractory neuroblastoma.

Implementation of a telemedical urgency assessment procedure in the pediatric emergency room: evaluation results.

Background: In rural areas in Germany, the number of emergency departments with pediatric expertise decreases. Telemedicine solutions are used sporadically, but they lack certain parameters for assessing a child's health status, such as touch and smell. We tested and evaluated the implementation of a telemedical, cross-hospital urgency assessment in pediatric emergency rooms.

Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers.

Purpose: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers.

Experimental Design: We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response and cytolytic effector functions in the tumor microenvironment. To allow stratification of patients according to tumor GD2 expression, we established and validated immunofluorescence detection of GD2 on paraffin-embedded tumor tissues.

Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression.

We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1-2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.

Multimodal Therapy with Consolidating Haploidentical Stem Cell Transplantation and Dinutuximab Beta for Patients with High-Risk Neuroblastoma and Central Nervous System Relapse.

Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse who received multimodal therapy with consolidating haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta ± subcutaneous interleukin-2 (scIL-2). Following individual relapse treatment, patients aged 1-21 years underwent haplo-SCT with T/B-cell-depleted grafts followed by dinutuximab beta 20 mg/m/day × 5 days for 5-6 cycles.

Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study.

Background: Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma.

Methods: In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles.

Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy.

The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. We conducted a retrospective clinical chart review of 25 patients with relapsed/refractory neuroblastoma who had failed ≥1 second-line therapy and received compassionate use treatment with dinutuximab beta long-term infusion combined with the induction chemotherapy regimens N5 (cisplatin, etoposide, vindesine) and N6 (vincristine, dacarbazine, ifosfamide, doxorubicin) recommended by the German Pediatric Oncology and Hematology Group [GPOH] guidelines.

Combined Blockade of TIGIT and PD-L1 Enhances Anti-Neuroblastoma Efficacy of GD2-Directed Immunotherapy with Dinutuximab Beta.

Immunotherapies against high-risk neuroblastoma (NB), using the anti-GD2 antibody (Ab) dinutuximab beta (DB), significantly improved patient survival. Ab-dependent cellular cytotoxicity (ADCC) is one of the main mechanisms of action and it is primarily mediated by NK cells. To further improve antitumor efficacy, we investigated here a combinatorial immunotherapy with DB and the double immune checkpoint blockade of T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death ligand-1 (PD-L1).

Endoscope-assisted microsurgical resection of a third ventricular immature teratoma.

Background: Reaching a tumor within the third ventricle is challenging, and planning an accessible trajectory is crucial without injuring the surrounding structures. We report a 5-year-old boy presented with headache and a seizure where sequential MRI brain studies in a short time period revealed a rapid growing immature teratoma within the third ventricle with hydrocephalic changes. Several management procedures were performed for CSF diversion and medical treatment of the tumor with chemotherapy and stem cell therapy.

Rare clival localization of an eosinophilic granuloma: illustrative case.

Background: Eosinophilic granuloma (EG) belongs to the family of Langerhans cell histiocytosis (LCH) and is considered to be a benign disease typically found in children younger than 15 years of age. Here, the authors describe an EG of unusual localization and clinical presentation.

Observations: The authors report a 9-year-old girl with an EG presenting as an osteolytic lesion of the clivus.

Pediatric Hematology and Oncology Center Integrated by Telemedicine: Experience, Challenges and First Results of a Cross Border Network.

This article reports on the development, implementation and management of a German-Polish telemedicine network in the field of pediatric oncology and hematology in the Euroregion Pomerania. The achievements and challenges of joint medical case reviews involving patients and their care givers, as well as cross-border education activities for physicians, students and nursing staff, are presented. In addition to a progress report, the results of an evaluation of the participants and teachers, likewise the measurement of knowledge growth, are given.

Quantitative Diffusion-Weighted MRI of Neuroblastoma.

Neuroblastoma is the most common extracranial, malignant, solid tumor found in children. In more than one-third of cases, the tumor is in an advanced stage, with limited resectability. The treatment options include resection, with or without (neo-/) adjuvant therapy, and conservative therapy, the latter even with curative intent.

Anti-GD2 Antibody Dinutuximab Beta and Low-Dose Interleukin 2 After Haploidentical Stem-Cell Transplantation in Patients With Relapsed Neuroblastoma: A Multicenter, Phase I/II Trial.

Purpose: Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). This phase I/II trial assessed safety, feasibility, and outcomes of immunotherapy with DB plus subcutaneous interleukin-2 (scIL2) after haplo-SCT in patients with rHR-NB.

Dinutuximab beta combined with chemotherapy in patients with relapsed or refractory neuroblastoma.

Prognosis in children with refractory and relapsed high-risk neuroblastoma is poor. Only a minority of patients obtain remission when treated with second-line chemotherapy regimens. Chemotherapy combined with anti-GD2 antibodies has previously been shown to increase response and survival rates.

Chemotherapeutics Used for High-Risk Neuroblastoma Therapy Improve the Efficacy of Anti-GD2 Antibody Dinutuximab Beta in Preclinical Spheroid Models.

Anti-disialoganglioside GD2 antibody ch14.18/CHO (dinutuximab beta, DB) improved the outcome of patients with high-risk neuroblastoma (HR-NB) in the maintenance phase. We investigated chemotherapeutic compounds used in newly diagnosed patients in combination with DB.

Combination of GD2-directed bispecific trifunctional antibody therapy with Pd-1 immune checkpoint blockade induces anti-neuroblastoma immunity in a syngeneic mouse model.

Introduction: Despite advances in treating high-risk neuroblastoma, 50-60% of patients still suffer relapse, necessitating new treatment options. Bispecific trifunctional antibodies (trAbs) are a promising new class of immunotherapy. TrAbs are heterodimeric IgG-like molecules that bind CD3 and a tumor-associated antigen simultaneously, whereby inducing a TCR-independent anti-cancer T cell response.

Splenic rupture and fungal endocarditis in a pediatric patient with invasive fusariosis after allogeneic hematopoietic stem cell transplantation for aplastic anemia: A case report.

Background: Invasive mold infections are a well-known and life-threatening condition after allogeneic hematopoietic stem cell transplantation (HSCT). While species are recognized as predominant pathogens, species should also be considered due to their broad environmental distribution and the expected poor outcome of invasive fusariosis. Particularly, splenic rupture as a complication of disseminated disease has not been reported yet.

BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells.

BCL11B, an essential transcription factor for thymopoiesis, regulates also vital processes in post-thymic lymphocytes. Increased expression of BCL11B was recently correlated with the maturation of NK cells, whereas reduced BCL11B levels were observed in native and induced T cell subsets displaying NK cell features. We show that BCL11B-depleted CD8+ T cells stimulated with IL-15 acquired remarkable innate characteristics.

Immune Response and Outcome of High-Risk Neuroblastoma Patients Immunized with Anti-Idiotypic Antibody Ganglidiomab: Results from Compassionate-Use Treatments.

(1) Background: High-risk neuroblastoma (HR-NB) is associated with a poor prognosis despite a multimodal high-intensity treatment regimen, including immunotherapy with anti-GD2 monoclonal antibodies (mAb). Here, we investigated the effects of an anti-idiotypic vaccine based on the mAb ganglidiomab that structurally mimics GD2. (2) Methods: Patients with HR-NB treated with anti-GD2 mAb dinutuximab beta and who achieved complete remission after frontline or salvage therapy were offered the vaccine (0.

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients.

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB.