Returning to daily life: a qualitative interview study on parents of childhood cancer survivors in Germany.

Objectives: To investigate experiences of parents of paediatric cancer survivors in cancer-related changes in the parents' daily life (work life, family life, partner relationship and social life) during and after intensive cancer treatment and to examine the reintegration process with its impeding and facilitating factors.

Design: The design of this cross-sectional study involves a qualitative content analysis of semistructured interviews.

Setting: Participants were consecutively recruited in clinical settings throughout Germany.

Novel Gene Mutation in a Case of Abetalipoproteinemia with Central Hypothyroidism.

Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive.

Results of CoALL 07-03 study childhood ALL based on combined risk assessment by in vivo and in vitro pharmacosensitivity.

We conducted a clinical trial and report the long-term outcome of 773 children with acute lymphoblastic leukemia upon risk-adapted therapy accrued in trial CoALL 07-03 (from the Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia). In a 2-step stratification, patients were allocated to receive either low- or high-risk treatment, based on initial white blood cell count, age, and immunophenotype. A second stratification was performed according to the results of in vitro pharmacosensitivity toward prednisolone, vincristine, and asparaginase (PVA score) and in vivo response after induction therapy (minimal residual disease [MRD]).

Pediatric ALL relapses after allo-SCT show high individuality, clonal dynamics, selective pressure, and druggable targets.

Survival of patients with pediatric acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-SCT) is mainly compromised by leukemia relapse, carrying dismal prognosis. As novel individualized therapeutic approaches are urgently needed, we performed whole-exome sequencing of leukemic blasts of 10 children with post-allo-SCT relapses with the aim of thoroughly characterizing the mutational landscape and identifying druggable mutations. We found that post-allo-SCT ALL relapses display highly diverse and mostly patient-individual genetic lesions.

Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

Background: Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the intensive care unit (ICU) is challenged by the clinical overlap with sepsis.

Recommendations for the management of hemophagocytic lymphohistiocytosis in adults.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH).

IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia.

IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r).

Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial.

Background: The EsPhALL2004 randomised trial showed a 10% advantage in disease-free survival for short, discontinuous use of imatinib after induction compared with no use of imatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia receiving Berlin-Frankfurt-Münster chemotherapy and haemopoietic stem-cell transplantation (HSCT). Other contemporary studies showed an advantage from continuous protracted exposure to imatinib, challenging the indications to transplant. The EsPhALL2010 study was designed to assess whether imatinib given from day 15 of induction and continuously throughout chemotherapy led to a different outcome to that obtained in EsPhALL2004, despite decreasing the number of patients having HSCT.

Trypsin-encoding variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.

Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten trial groups contributed remission samples from patients aged 1.0-17.

PDX models recapitulate the genetic and epigenetic landscape of pediatric T-cell leukemia.

We compared 24 primary pediatric T-cell acute lymphoblastic leukemias (T-ALL) collected at the time of initial diagnosis and relapse from 12 patients and 24 matched patient-derived xenografts (PDXs). DNA methylation profile was preserved in PDX mice in 97.5% of the promoters (ρ = 0.

Long-term Dental Anomalies after Pediatric Cancer Treatment in Children.

Objective: The aim of this study is to determine the frequency of dental anomalies (DAs) (microdontia, hypodontia, hyperdontia, enamel defect, root malformation) in pediatric cancer patients at the ages <5 years and between 5 and 7 years, and understand their relationship with the received therapy.

Materials And Methods: Pediatric patients who were diagnosed with cancer and treated before the age of 7 years were investigated in a case- control design. The study included 93 pediatric patients whose ages at diagnosis were between 9 months and 7 years and whose treatments were completed before 5-8 years.

Recommendations for the Use of Etoposide-Based Therapy and Bone Marrow Transplantation for the Treatment of HLH: Consensus Statements by the HLH Steering Committee of the Histiocyte Society.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome requiring aggressive immunosuppressive therapy. Following 2 large international studies mainly targeting pediatric patients with familial disease and patients without underlying chronic or malignant disease, the HLH-94 protocol is recommended as the standard of care when using etoposide-based therapy by the Histiocyte Society. However, in clinical practice, etoposide-based therapy has been widely used beyond the study inclusion criteria, including older patients and patients with underlying diseases (secondary HLH).

Pediatric acute lymphoblastic leukemia-Conquering the CNS across the choroid plexus.

Despite the high prevalence of central nervous system (CNS) involvement in relapsing pediatric acute lymphoblastic leukemia (ALL), our understanding of CNS invasion is still vague. As lymphoblasts have to overcome the physiological blood-CNS barriers to enter the CNS, we investigated the cellular interactions of lymphoblasts with the choroid plexus (CP) epithelium of the blood-cerebrospinal fluid barrier (BCSFB). Both a precurser B cell ALL (pB-ALL) cell line (SD-1) and a T cell ALL (T-ALL) cell line (P12-Ishikawa) were able to actively cross the CP epithelium in a human in vitro model.

Daunorubicin during delayed intensification decreases the incidence of infectious complications - a randomized comparison in trial CoALL 08-09.

Anthracyclines are integral components of antileukemic treatment. Apart from cardiotoxicity, myelosuppression and infectious complications have been described for doxorubicin (DOX) and daunorubicin (DNR) as predominant side effects, but little is known about their differential toxicities. To address the question whether DNR is associated with a lower rate of infectious complications compared with DOX, 307 children with newly diagnosed acute lymphoblastic leukemia, enrolled in trial CoALL 08-09, were randomized to receive either DOX 30 mg/m (n = 153) or DNR 36 mg/m (n = 154) in delayed intensification.

Aplastic Anemia as an Immune-mediated Complication of Thymoma: A Case Report.

Thymomas are the most common masses located in the anterior mediastinum, and they are often associated with autoimmune disorders including myasthenia gravis, polymyositis, and aplastic anemia (AA). Autoreactive T-cell clones generated by the thymoma may lead to autoimmune disorders. We report the case of a 14-year-old boy who was examined for AA, and the underlying cause was determined to be an immune-mediated complication of thymoma.

Imatinib in the treatment of chronic myeloid leukemia in children and adolescents is effective and well tolerated: Report of the Polish Pediatric Study Group for the Treatment of Leukemias and Lymphomas.

Background: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children.

Inflammatory myofibroblastic tumors-A retrospective analysis of the Cooperative Weichteilsarkom Studiengruppe.

Background: Inflammatory myofibroblastic tumors (IMTs) are a rare subgroup of soft tissue tumors. The outcome of patients with IMT has been reported as favorable when the tumor is completely resected. If surgical resection is not possible, systemic therapy has to be considered.

Corrigendum: Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

[This corrects the article on p. 449 in vol. 8, PMID: 28507545.