Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa-Results of the HIT 2000 trial.

Background: Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization, and biology in pediatric survivors of a posterior fossa tumor.

Methods: Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic tool based on Cattell-Horn-Carroll's model for intelligence were analyzed.

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.

A case report of Sanfilippo syndrome - the long way to diagnosis.

Background: Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated.

Refining M1 stage in medulloblastoma: criteria for cerebrospinal fluid cytology and implications for improved risk stratification from the HIT-2000 trial.

Background: Medulloblastoma is the most common malignant paediatric brain tumour, and cerebrospinal fluid (CSF) dissemination (M1 stage) is a high-risk prognostic factor. Criteria for CSF evaluation and for differentiating M0 from M1 stage are not clearly defined, and the prognostic significance of M1 stage in this context is unknown.

Patients And Methods: CSF investigations from 405 patients with medulloblastoma of the prospective multicenter trial HIT-2000 (HIirnTumor-2000) were reviewed.

Impact of Lymphadenectomy on the Oncologic Outcome of Patients with Adrenocortical Carcinoma-A Systematic Review and Meta-Analysis.

(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement.

Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.

Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled.

Pediatric hypophosphatasia: lessons learned from a retrospective single-center chart review of 50 children.

Background: Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all ages.

Persistent tachypnea of infancy: Follow up at school age.

Background: Persistent tachypnea of infancy (PTI) is a rare pediatric lung disease of unknown origin. The diagnosis can be made by clinical presentation and chest high resolution computed tomography after exclusion of other causes. Clinical courses beyond infancy have rarely been assessed.

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort.

Purpose: The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.

Patients And Methods: From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression.

Correction to: Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis.

Following publication of the original article [1], we have been notified that the authors' first names and last names are presented in wrong order. The presentation of names, thus, should be as follows.

Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis.

Background: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system of yet unknown etiology. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physical activity, fitness and health-related quality of life (HRQOL) in adolescents with established diagnosis of CNO versus healthy controls (HC).

Pediatric Colorectal Carcinoma is Associated With Excellent Outcome in the Context of Cancer Predisposition Syndromes.

Introduction: Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage.

Method: Thirty-one patients with CRC age ≤ 18 years and treated between 1990 and 2012 have been identified through the structures and registries of the German Society for Pediatric Oncology and Hematology.

Multiple Antenatal Dexamethasone Treatment Alters Brain Vessel Differentiation in Newborn Mouse Pups.

Antenatal steroid treatment decreases morbidity and mortality in premature infants through the maturation of lung tissue, which enables sufficient breathing performance. However, clinical and animal studies have shown that repeated doses of glucocorticoids such as dexamethasone and betamethasone lead to long-term adverse effects on brain development. Therefore, we established a mouse model for antenatal dexamethasone treatment to investigate the effects of dexamethasone on brain vessel differentiation towards the blood-brain barrier (BBB) phenotype, focusing on molecular marker analysis.

Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning.

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013.

Successful treatment of an infant with CDA type II by intrauterine transfusions and postnatal stem cell transplantation.

Congenital dyserythropoietic anemias are rare hematological disorders leading to ineffective erythropoiesis with chronic anemia, complicated by iron overload. Here we present a remarkable clinical course of an infant with CDA type II who first presented as a severe fetal hydrops, requiring serial intrauterine red cell transfusions. While postnatal transfusion dependency persisted, the patient was successfully transplanted with a myeloablative conditioning regimen and peripheral blood stem cells of a matched donor.

Indication for allogeneic stem cell transplantation in Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder characterized by a lack of thrombocyte aggregation due to the absence of thrombocyte glycoproteins IIb and αIIbβ3. The role of haematopoietic stem cell transplantation (HSCT) in GT remains controversial. However, HSCT offers the only curative approach for patients with a severe clinical phenotype.

Immune function in newly diagnosed children with malignancy.

Background: Tumor genesis of many pediatric malignancies remains unclear. Data of immune function are lacking at diagnosis. We prospectively analyzed 109 pediatric patients with malignancy at diagnosis.

Varicella-zoster virus infections in immunocompromised patients - a single centre 6-years analysis.

Background: Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZV-immunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses.

Methods: In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZV-infections in our center and compare them to published data.

Age-related changes in intracellular cytokine expression in healthy children.

Cytokine production by human lymphocytes from healthy children (ages 0-18 years) was assessed using a flow cytometric procedure involving staining of intracellular cytokines by the paraformaldehyde-saponin procedure. To establish valid cytokine values for intracellular cytokine expression in healthy children in the different age groups, we measured 117 samples after 24 h in vitro stimulation with PMA, ionomycin and brefeldin followed by staining with intracellular anti-cytokine and surface antibodies. We found decreasing IL-2 expression, increasing IFN-gamma and TNF-alpha production and stable IL-4, Ki67 and TGFb levels with advancing age.