Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

[Langerhans cell histiocytosis with atypical and early neonatal debut]. / Histiocitosis de células de Langerhans con debut neonatal atipico y precoz.

Langerhans cell histiocytosis is a systemic disease associated with the proliferation of this type of cells in tissues. Its prevalence is estimated at 1-9/100 000. Bone is the most frequently affected organ, followed by the skin, lymph nodes, haematopoietic system, pituitary gland, lungs and liver. In the majority of cases, onset occurs during childhood, with peak between one and three years of age, and poor prognosis before two years of age. The haematological forms (pancytopenia) are usually aggressive in infants. We report a case of Langerhans cell histiocytosis with neonatal onset and complex diagnosis: maintained and significant leukocytosis was the predominant data for the first two months of life, so some type of leukemia was considered. However, the most common blood disorder in Langerhans cell histiocytosis is pancytopenia rather than leukocytosis, so that the diagnosis was delayed.

La histiocitosis de células de Langerhans es una enfermedad sistemica asociada con la proliferación de este tipo de células en distintos tejidos. La prevalencia estimada es de 1-9/100 000. El órgano más frecuentemente afectado es el hueso, seguido por la piel, ganglios linfáticos, sistema hematopoyético, hipófisis, pulmones e hígado. En la mayoría de los casos, la enfermedad debuta en la infancia, con pico entre uno y tres años de edad, y tiene mal pronóstico cuando ocurre antes de los dos años. La afectación del sistema hematopoyético, manifestada en forma de pancitopenia, suele ser agresiva en los lactantes. Se presenta un caso de histiocitosis de células de Langerhans con debut neonatal y complejo diagnóstico, ya que, los dos primeros meses de vida, el dato predominante era una leucocitosis importante mantenida que obligaba a descartar alguna forma de leucemia, mientras que la alteración hematológica más frecuente en la histiocitosis de células de Langerhans, como se ha comentado, es la pancitopenia, lo que motivó un retraso en el diagnóstico.

Histiocitosis de células de Langerhans con debut neonatal atipico y precoz / Langerhans cell histiocytosis with atypical and early neonatal debut

La histiocitosis de células de Langerhans es una enfermedad sistemica asociada con la proliferación de este tipo de células en distintos tejidos. La prevalencia estimada es de 1-9/100 000. El órgano más frecuentemente afectado es el hueso, seguido por la piel, ganglios linfáticos, sistema hematopoyético, hipófisis, pulmones e hígado. En la mayoría de los casos, la enfermedad debuta en la infancia, con pico entre uno y tres años de edad, y tiene mal pronóstico cuando ocurre antes de los dos años. La afectación del sistema hematopoyético, manifestada en forma de pancitopenia, suele ser agresiva en los lactantes. Se presenta un caso de histiocitosis de células de Langerhans con debut neonatal y complejo diagnóstico, ya que, los dos primeros meses de vida, el dato predominante era una leucocitosis importante mantenida que obligaba a descartar alguna forma de leucemia, mientras que la alteración hematológica más frecuente en la histiocitosis de células de Langerhans, como se ha comentado, es la pancitopenia, lo que motivó un retraso en el diagnóstico.

Langerhans cell histiocytosis is a systemic disease associated with the proliferation of this type of cells in tissues. Its prevalence is estimated at 1-9/100 000. Bone is the most frequently affected organ, followed by the skin, lymph nodes, haematopoietic system, pituitary gland, lungs and liver. In the majority of cases, onset occurs during childhood, with peak between one and three years of age, and poor prognosis before two years of age. The haematological forms (pancytopenia) are usually aggressive in infants. We report a case of Langerhans cell histiocytosis with neonatal onset and complex diagnosis: maintained and significant leukocytosis was the predominant data for the first two months of life, so some type of leukemia was considered. However, the most common blood disorder in Langerhans cell histiocytosis is pancytopenia rather than leukocytosis, so that the diagnosis was delayed.

Neonatal fulminant type 2 infantile hepatic hemangioendothelioma involving skin, viscera and soft tissue.

We present the fulminant case of a neonate whose symptoms, lesions, imaging, and laboratory tests perfectly simulated a neonatal neuroblastoma and the definitive diagnosis was finally given by necropsy as follows: Infantile hepatic hemangioendothelioma type 2 with extrahepatic extension affecting skin, lung, intestine, suprarenal, and soft tissue.