Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia.

We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective "off-the-shelf" immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.

Systemic granulomatosis after surgical injection of silicone oil for retinal detachment in a child affected by Fisher-Evans syndrome.

UNLABELLED: Silicone oil is used for complicated retinal detachment, but it can be associated with relevant side effects. We report a 6-year-old South American female admitted to our hospital with steroid-resistant Fisher-Evans syndrome. She also had developed a retinal detachment, managed with intravitreal oil injection. During treatment for Fisher-Evans syndrome, she progressively developed recurrent and refractory bronchospasm, peaks of hypereosinophilia and orbital soft-tissue swelling. Despite the persistent negativity of all microbiologic tests, she was treated empirically with antibiotics. Failure of the treatment led to the execution of a biopsy of the periocular tissue that revealed an intense polymorphous infiltrate constituted by numerous monoclonal population (FR2 monoclonality) of plasma-cells. A diagnosis of lymphoma with plasmacytoid differentiation was suspected and cytotoxic treatment was started without response. For the appearance of swelling in left parotid and laterocervical region, an excisional biopsy was performed and a diagnosis of granulomatous reaction to ocular implant of silicone oil was made. In consideration of the clinical evolution, enucleation was considered, but parents did not consent to the procedure until the child developed cerebral lesions suspected to be silicone localizations. After enucleation, eosinophilic count normalized and the child no longer presented any new episode of fever or swelling. CONCLUSIONS: In this patient a granulomatous reaction is present at distance from the site of oil injection. This case suggests caution in using this substance even in ocular diseases, especially in immunocompromised patients.

Diet and physical activity "defeated" Tuberil® in treatment of childhood obesity.

AIM: Childhood obesity is remarkably spreading worldwide, involving both industrialized and low-income countries. Its prevalence, outcome and socioeconomic impact call for the attention of medical community. We conducted a monocentric, open, two-arm, parallel-group study to evaluate the efficacy at reducing appetite and increasing dietary compliance of obese children of Tuberil®, a weight-loss supplement derived from potato and devoid of side effects. METHODS: We recruited participants, children with BMI ≥ 85th, through direct referrals in pediatrician's surgeries. Children were randomized to receive Tuberil® (group A) or nothing (group B), following a chronological order (A-B-A-B). Every child received a nutritionally balanced diet and had to record their appetite and to describe their meals in a diary. RESULTS: Even if we found a significant reduction in BMI, weight and waist circumference in both groups, no statistically significant differences between groups were noted. We did not found any significant differences in appetite between group A and B. CONCLUSION: Our data show that Tuberil® has no efficacy neither in reducing appetite in children nor in increasing dietary compliance. We believe that only a nutritionally balanced diet and our attention in verifying their compliance led to the reduction in BMI, weight and waist circumferences noted in our series.

Wolf-Hirschhorn syndrome with improvement of renal function.

Wolf-Hirschhorn syndrome (WHS) is a chromosomal disorder characterized by partial deletion of the short arm of chromosome 4. We describe a girl with a de novo unbalanced traslocation t(4;7)(p16.2;p22), associated with a mild version of a classical WHS phenotype. She did not present major urinary tract abnormalities but had parenchymal hyperechogenicity at renal ultrasound at the birth with normal renal scintigraphy. She had also a reduction of GFR with elevated levels of blood urea nitrogen and serum potassium until the age of 6 months. We followed the patient with periodic clinical examination and laboratory and radiological investigations and observed at the age of 5 years a normal renal ultrasound without parenchymal hyperechogenicity.