Over the past decades, survival of patients with acute lymphoblastic leukemia (ALL) has dramatically improved, but the subgroup of patients with relapsed/refractory ALL still continues to have dismal prognosis. As an emerging therapeutic approach, chimeric antigen receptor-modified T-cells (CAR-T) represent one of the few practice-changing therapies for this subgroup of patients. Originally conceived and built in Philadelphia (University of Pennsylvania), CTL019 or tisagenlecleucel, the first CAR-T approved by the US Food and Drug Administration, showed impressive results in refractory/relapsed ALL since the publication on two pediatric patients in 2013. It is in this context that we provide a review of this product in terms of manufacturing, pharmacology, toxicity, and efficacy studies. Evaluation and management of toxicities, particularly cytokine release syndrome and neurotoxicity, is recognized as an essential part of the patient treatment with broader use of IL-6 receptor inhibitor. An under-assessed aspect, the quality of life of patients entering CAR-T cells treatment, will also be reviewed. By their unique nature, CAR-T cells such as tisagenlecleucel operate in a different way than typical drugs, but also provide unique hope for B-cell malignancies.

Non-epithelial ovarian tumours are rare neoplasms that occasionally arise in childhood and adolescence. They can be associated with various cancer susceptibility syndromes. The morphological overlap seen across these tumours and their rarity can make the diagnosis challenging. In the case of an incorrect diagnosis, the underlying genetic susceptibility may be missed. In this review, we outline the genetic background of ovarian non-epithelial tumours arising in children, emphasizing the genes harbouring pathogenic germline variants associated with each tumour type. Specifically, juvenile granulosa cell tumours, Sertoli-Leydig cell tumours, sex cord tumours with annular tubules, Sertoli cell tumours, germ cell tumours and small cell carcinoma of the ovary of hypercalcaemic type are discussed in this review. For each tumour type, we detail the personal and family history features and the presenting characteristics of the ovarian tumour as well as the pathological features and molecular markers that point towards a cancer predisposition syndrome. Throughout, we stress the need for specialised pathological review in difficult cases.

No abstract

During recent decades, the prognosis of childhood acute lymphoblastic leukemia (ALL) has improved dramatically, nowadays, reaching a cure rate of almost 90%. These results are due to a better management and combination of old therapies, refined risk-group stratification and emergence of minimal residual disease (MRD) combined with treatment's intensification for high-risk subgroups. However, the subgroup of patients with refractory/relapsed ALL still presents a dismal prognosis indicating necessity for innovative therapeutic approaches. Areas covered: We performed an exhaustive review of current first-line therapies for childhood ALL in the worldwide main consortia, summarized the major advances for front-line and relapse treatment and highlighted recent and promising innovative therapies with an overview of the most promising ongoing clinical trials. Expert opinion: Two major avenues marked the beginning of 21 century. First, is the introduction of tyrosine-kinase inhibitor coupled to chemotherapy for treatment of Philadelphia positive ALL opening new treatment possibilities for the recently identified subgroup of Ph-like ALL. Second, is the breakthrough of immunotherapy, notably CAR T-cell and specific antibody-based therapy, with remarkable success observed in initial studies. This review gives an insight on current knowledge in these innovative therapeutic directions, summarizes currently ongoing clinical trials and addresses challenges these approaches are faced with.