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.

Methylation-associated PHOX2B gene silencing is a rare event in human neuroblastoma.

Neuroblastoma (NB), an embryonic tumour originating from neural crest cells, is one of the most common solid tumours in childhood. Although NB is characterised by numerous recurrent, large-scale chromosome rearrangements, the genes targeted by these imbalances have remained elusive. We recently identified the paired-like homeobox 2B (PHOX2B, MIM 603851) gene as disease-causing in dysautonomic disorders including Congenital Central Hypoventilation Syndrome (CCHS), Hirschsprung disease (HSCR) and NB in various combinations.

High-dose chemotherapy in childhood brain tumours.

New therapeutic strategies are required to improve the prognosis of malignant brain tumours in children, in terms of survival and quality of life. During the last 10 years, high-dose chemotherapy (HDCT) with autologous haematopoietic stem cell rescue has been studied in different types of paediatric brain tumours. The most frequently used combined regimens were busulfan-thiotepa and etoposide-thiotepa along with carboplatin or BCNU.

[Large cell variant of small cell carcinoma of the ovary with hypercalcemia].

We describe an original distinct type of ovarian small cell carcinoma: large cell variant. The distinctive histologic features of tumor cells were the presence of large nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry revealed strong diffuse vimentin, smooth muscle actin positivity and slight reactivity with epithelial markers.

T-cell receptor repertoire in neuroblastoma patients.

Spontaneous regression of widespread lesions is a characteristic feature of neuroblastoma. One may postulate that the immune response contributes to these clinical regressions. Accordingly, we studied the T-cell receptor (TCR) repertoire of tumor-infiltrating lymphocytes in eight neuroblastoma tumors.