Hematopoietic stem cell transplantation for inborn errors of immunity: 30-year single-center experience.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an effective treatment for a variety of inborn errors of immunity (IEI). We report the experience of children affected by IEI who received allo-HSCT over a period of 32 years at IRCCS Istituto Giannina Gaslini, Genoa, Italy. HSCTs were performed in 67 children with IEI. Kaplan-Meier estimates of overall survival (OS) rate at 5 years in the whole group of patients was 83.4% after a median follow-up of 4 years. Median age at transplant was 2.5 years. Eight allo-HSCTs were complicated by either primary or secondary graft failure (GF), the overall incidence of this complication being 10.9%. Incidence of grade 3-4 acute GvHD (aGvHD) was 18.7%, significantly lower in the haploidentical transplant cohort (p = 0.005). Year of transplant (≤2006 vs. >2006) was the main factor influencing the outcome. In fact, a significant improvement in 5-year OS was demonstrated (92.5% >2006 vs. 65% ≤2006, p = 0.049). Frequency of severe aGvHD was significantly reduced in recent years (≤2006 61.5%, vs. >2006 20%, p = 0.027). A significant progress has been the introduction of the TCR αß/CD19-depleted haploidentical platform, which was associated with the absence of severe aGvHD. However, it was associated with 23.5% incidence of GF. All but one patient experiencing GF in the this specific cohort were successfully retransplanted. In summary, allo-HSCT is confirmed to be an effective treatment for children with IEI, even in the absence of an HLA-matched donor.

Prophylaxis of Invasive Fungal Infection in Neonates: A Narrative Review for Practical Purposes.

Candida albicans is the most frequent cause of invasive fungal disease in preterm and/or low birth weight neonates, followed by Candida parapsilosis, whilst infections from other species are rare. Considering the severity of the disease, associated with poor clinical signs and diagnostic difficulties, primary prophylaxis becomes relevant. This paper summarizes the pathogenesis and clinical presentation of invasive candidiasis in neonates, focusing on prophylaxis. For late onset invasive disease, e.g., those occurring after the 3rd (or 7th according to some definitions) day of life possible approaches are the use of fluconazole, recommended in case of weight <1000 g or <1500 g if the local incidence of invasive candidiasis is higher than 2%, or the use of nystatin (for patients < 1500 g). Micafungin must be used in case of colonization by Candida auris, or in centers with a high prevalence of this pathogen. Concurrently, correct management of the central venous catheter and isolation procedures, with special regard to patients colonized by resistant strains, are fundamental. Other approaches such as reduced use of H2 blockers and broad-spectrum antibiotics (e.g., 3rd generation cephalosporins or carbapenems) and promotion of breast feeding proved useful. Reduction of early-onset infections (those occurring in the first 3 days of life) can also be obtained by treating maternal vulvo-vaginal candidiasis, which can represent a fastidious problem during pregnancy. In this case, topic azoles (the only recommendable treatment) can represent a kind of "prophylaxis" of early neonatal candidiasis. However, it must always be remembered that prophylaxis reduces the risk of invasive candidiasis but can not completely eliminate its occurrence, with the parallel risk of selecting for antifungal-resistant strains. Clinicians must maintain a high level of suspicion to start an appropriate therapy and strict epidemiological surveillance to identify the occurrence of clusters and the appearance of strains resistant to prophylaxis.

Type 1 Diabetes and Addison's Disease: When the Diagnosis Is Suggested by the Continuous Glucose Monitoring System.

Our objective is to emphasize the important role of continuous glucose monitoring (CGM) in suggesting adrenal insufficiency in patients affected by type 1 diabetes. We describe an adolescent girl with type 1 diabetes and subsequent latent Addison's disease diagnosed based on a recurrent hypoglycemic trend detected by CGM. In patients with type 1 diabetes, persistent unexplained hypoglycemic episodes at dawn together with reduced insulin requirement arouse souspicionof adrenal insufficiency. Adrenal insufficiency secondary to autoimmune Addison's disease, even if rarely encountered among young patients, may be initially symptomless and characterized by slow progression up to acute adrenal crisis, which represents a potentially life-threatening condition. Besides glycometabolic assessment and adequate insulin dosage adjustment, type 1 diabetes needs prompt recognition of potentially associated autoimmune conditions. Among these, Addison's disease can be suspected, although latent or paucisymptomatic, through periodic and careful evaluation of CGM data.