Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series

Background Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6–NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. Objective To report our experience with the use of larotrectinib in pediatric patients. Methods Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. Results Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. Conclusion Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations (AU)

Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series.

BACKGROUND: Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6-NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. OBJECTIVE: To report our experience with the use of larotrectinib in pediatric patients. METHODS: Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. RESULTS: Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. CONCLUSION: Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations.

Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice-site mutations: Two case reports and a literature review.

The clinical and laboratory criteria for hemophagocytic lymphohistiocytosis should be taken into account during the juvenile myelomonocytic leukemia diagnosis, specifically in CBL syndrome, to reveal the presence of primary rather than secondary associated hemophagocytosis.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.

Más allá de las células CAR-T, inmunoterapia con linfocitos natural killer / Beyond CAR-T cells: Natural killer cells immunotherapy

A pesar de la mejoría en el pronóstico del cáncer infantil, la recaída o la refractariedad a los tratamientos convencionales todavía condicionan un mal pronóstico. En el momento actual, la investigación en el área de la inmunoterapia, con medicamentos como los inhibidores de puntos críticos de control inmunitario y los linfocitos T modificados genéticamente, tisagenlecleucel o axicabtagene ciloleucel, están revolucionando el tratamiento del cáncer. En paralelo, se están desarrollando otras inmunoterapias, como la terapia celular con linfocitos natural killer (NK). La rápida y potente actividad citotóxica de las células NK respetando las células sanas y la posibilidad de expandirlas, manipularlas y combinarlas con otros tratamientos, hacen de estas células una poderosa herramienta terapéutica a desarrollar, con un perfil de seguridad muy alto. Además, se están desarrollando nuevas estrategias para incrementar el beneficio terapéutico de estas células, como la manipulación genética para la expresión de receptores de antígeno quiméricos

Children and adolescents suffering from refractory leukaemia, relapse after stem cell transplantation, solid metastatic tumour or refractory to conventional treatments still condition a dismal prognosis. The critical role of the immune system in the immunosurveillance of cancer is becoming relevant with the development of new treatments such as the checkpoint inhibitor drugs and genetic modified T lymphocytes, tisagenlecleucel or axicabtagene ciloleucel. In addition, other immunotherapies are being developed such as cell therapy with natural killer (NK) lymphocytes. The rapid and potent cytotoxic activity of NK cells respecting healthy cells and the possibility of expansion, manipulating them and combining them with other treatments, make these cells a powerful therapeutic tool to be developed, with a very high safety profile. Furthermore, new strategies are being developed to increase the therapeutic benefit of NK cells such as genetic manipulation for the expression of chimeric antigen receptors

Beyond CAR-T cells: Natural killer cells immunotherapy. / Más allá de las células CAR-T, inmunoterapia con linfocitos natural killer.

Children and adolescents suffering from refractory leukaemia, relapse after stem cell transplantation, solid metastatic tumour or refractory to conventional treatments still condition a dismal prognosis. The critical role of the immune system in the immunosurveillance of cancer is becoming relevant with the development of new treatments such as the checkpoint inhibitor drugs and genetic modified T lymphocytes, tisagenlecleucel or axicabtagene ciloleucel. In addition, other immunotherapies are being developed such as cell therapy with natural killer (NK) lymphocytes. The rapid and potent cytotoxic activity of NK cells respecting healthy cells and the possibility of expansion, manipulating them and combining them with other treatments, make these cells a powerful therapeutic tool to be developed, with a very high safety profile. Furthermore, new strategies are being developed to increase the therapeutic benefit of NK cells such as genetic manipulation for the expression of chimeric antigen receptors.

Presentation of severe combined immunodeficiency with respiratory syncytial virus and pneumocystis co-infection.

Severe combined immunodeficiency can cause severe, life-threatening viral, bacterial and fungal infections at an early age. We report a case of a 4-month-old boy with co-infection by respiratory syncytial virus and Pneumocystis jiroveci infection that led to recognition of severe combined immunodeficiency.