Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies: ACCELERATE in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration.

The first (2017) and sixth (2021) multistakeholder Paediatric Strategy Forums focused on anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies. ALK is an important oncogene and target in several paediatric tumours (anaplastic large cell lymphoma [ALCL], inflammatory myofibroblastic tumour [IMT], neuroblastoma and hemispheric gliomas in infants and young children) with unmet therapeutic needs. ALK tyrosine kinase inhibitors have been demonstrated to be active both in ALK fusion-kinase positive ALCL and IMT.

[Registries and studies in the Society for Pediatric Oncology and Hematology (GPOH) - What contribution do they make to progress?].

Cancer in children and adolescents under the age of 18 is rare; in 2017, approximately 2220 new cases in Germany were reported to the German Childhood Cancer Registry. The aim of the GPOH has always been to treat as many affected patients as possible in a standardized way, preferably in prospective, controlled studies. The Joint Federal Committee has also laid down this requirement in the paediatric oncology guideline.

Non-anaplastic peripheral T-cell lymphoma in children and adolescents--a retrospective analysis of the NHL-BFM study group.

Mature (peripheral) T-cell lymphoma (PTCL) other than anaplastic large cell lymphoma is a heterogeneous group of diseases and exceedingly rare in children and adolescents. Survival rates range between 46% and 85%. This study reports the disease characteristics, treatment and outcome of all patients with the diagnosis of mature TCL registered in the Berlin-Frankfurt-Munster non-Hodgkin lymphoma database between 1986 and 2012.

Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster (BFM)-type first-line therapy: a BFM-group study.

Purpose: To evaluate risk factors for outcome in children and adolescents with relapse of anaplastic large-cell lymphoma (ALCL) after comparable first-line therapy.

Patients And Methods: We analyzed a population-based cohort of 74 children with relapsed ALCL after Berlin-Frankfurt-Muenster-type first-line therapy between April 1990 and December 2003. The recommended salvage strategy was reinduction chemotherapy followed by autologous hematopoietic stem-cell transplantation (SCT).

Inhibition of anaplastic lymphoma kinase (ALK) activity provides a therapeutic approach for CLTC-ALK-positive human diffuse large B cell lymphomas.

ALK positive diffuse large B-cell lymphomas (DLBCL) are a distinct lymphoma subtype associated with a poor outcome. Most of them feature a t(2;17) encoding a clathrin (CLTC)-ALK fusion protein. The contribution of deregulated ALK-activity in the pathogenesis and maintenance of these DLBCLs is not yet known.

Mini buffy coat photopheresis for children and critically ill patients with extracorporeal photopheresis contraindications.

Background: Conventional extracorporeal photopheresis (ECP) has proven efficacy for the treatment of several diseases but is limited to patients with sufficient body weight. A novel simplified mini buffy coat ECP technique that allows treatment of small children and patients with apheresis contraindications has been developed.

Study Design And Methods: White blood cell (WBC)-rich buffy coat fractions were prepared from 5 to 8 mL/kg whole blood in a closed system, diluted, and ultraviolet A (UVA)-irradiated after addition of 8-methoxypsoralen (8-MOP).

Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation.

Anaplastic large cell lymphomas (ALCL) in children express anaplastic lymphoma kinase (ALK) fusion genes, most commonly NPM1-ALK. The distribution of X-ALK among 66 childhood ALCLs was analysed. One ALCL was ALK-negative.

Flow cytometric detection of circulating tumour cells in nucleophosmin/anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: comparison with quantitative polymerase chain reaction.

Quantification of occult circulating tumour cells in blood or bone marrow (BM) enables the identification of patients with a high risk for relapse in nucleophosmin/anaplastic lymphoma kinase (NPM-ALK)-positive anaplastic large cell lymphoma (ALCL). We have developed a flow cytometric (FCM) assay to quantify the rare ALK- and CD30-positive ALCL cells. When ALCL cells were admixed with normal peripheral blood or BM, ALK- and CD30-positive cells could be detected above background level at an added concentration of 10(-5) for all three cell lines tested.

Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large-cell lymphoma.

Clinical and histopathological characteristics have limited prognostic value for children with anaplastic large-cell lymphoma (ALCL). We evaluated the presence, extent, and prognostic impact of circulating tumor cells in bone marrow (BM) and peripheral blood (PB) of children and adolescents with NPM-ALK-positive ALCL at diagnosis using qualitative and quantitative polymerase chain reaction (PCR) for NPM-ALK. Numbers of NPM-ALK transcripts were normalized to 10(4) copies ABL (NCNs).

Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Münster group report.

Patients with refractory or early relapsed anaplastic large cell lymphoma (ALCL) have a poor chance of survival. We report 20 children and adolescents with high-risk relapsed or refractory ALCL who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively analysed 20 patients who relapsed between December 1991 and April 2003 during (six patients) or soon after first-line Berlin-Frankfurt-Münster-type chemotherapy (14 patients) and underwent allogeneic HSCT.

ERK signaling pathway is differentially involved in erythroid differentiation of K562 cells depending on time and the inducing agent.

K562 cells can be induced to differentiate along the erythroid lineage by a variety of chemical compounds, including hemin, butyrate, cisplatin and ara-C. Differential signaling through MAP kinases has been suggested to be involved in this differentiation process. We have investigated the involvement of ERK activation/inhibition in hemin-, butyrate-, cisplatin- and ara-C-induced erythroid differentiation using the K562 cell line.

RNA interference: new mechanisms for targeted treatment?

Nucleic acid-based sequence-specific therapeutic intervention offers the potential for treatment of particular cancers without side effects. RNA interference (RNAi) induced by small interfering RNA (siRNA) (19-21 bp) is a normal cellular mechanism leading to highly specific and extraordinarily efficient degradation of the corresponding mRNA. The mechanism of RNAi as well as strategies for the design and delivery of siRNA are described.

Ras-mediated activation of ERK by cisplatin induces cell death independently of p53 in osteosarcoma and neuroblastoma cell lines.

Activation of the mitogen-activated protein kinases ERK1/2 by the chemotherapeutic agent cisplatin has been shown to result in either survival or cell death. The downstream mediators of these opposing effects are unknown, as are the upstream signaling molecules. Activation of ERK is required for accumulation and phosphorylation of p53 following cisplatin treatment.