DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

Lomentospora prolificans is a filamentous fungus and an emerging pathogen in immunocompromised patients. It is encountered most commonly in Australia, Spain, and USA. We described the first case of Lomentospora prolificans fungemia in South America. The patient was a hematopoietic stem cell transplantation (HSCT) recipient who developed the infection 37days after stem cells infusion. In addition, we performed a literature review of invasive lomentosporiosis in HSCT patients.

Hematopoietic stem cell transplantation (HSCT) is a curative alternative for patients with Chronic Granulomatous Disease (CGD), a primary immunodeficiency (PID) characterized by an inherited defect of the neutrophil function which can lead to life threatening infections and granulomas. Historically, HSCT with conventional myeloablative conditioning regimens has been associated with high toxicity for patients with CGD. More recently, International Working Groups on PID have published an experience with reduced toxicity regimen showing important improvements in transplant outcomes for these patients. We describe here the experience of our center with a reduced toxicity regimen for patients with CGD. Methods: We conducted a retrospective analysis of nine patients who underwent allogeneic HSCT for Chronic Granulomatous Disease at the Children's Institute of the University of São Paulo, using a reduced toxicity regimen. Results: From 2010 to May 2016, nine patients with CGD were submitted to HSCT in our center. Risk features pre-HSCT included: pulmonary aspergillosis, pulmonary tuberculosis, staphylococcal abscess, disseminated BCGosis, most having multiple severe infections and granulomas. Three of the patients had active infection at the moment of transplant. Median age at transplant was 7 years (range 1-14). Donors were: siblings (n = 3) or matched unrelated donors (MUD) (n = 6), considering HLA A, B, C and DRB1 (high resolution). Graft source was bone marrow for all 9 patients. All patients received the same preparative regimen consisting of: fludarabine 180 mg/m2, intravenous bussulfan (AUC range 45-65 mg/l*h) and either antithymocyte globulin (ATG) 7,5 mg/Kg (n = 7) or alemtuzumab 0,6 mg/Kg (n = 2). Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine A and mycophenolate. Post-transplantation complications included: mild mucositis (n = 6), acute GVHD grade II-III (n = 5; 4 = only skin and 1 = skin and gut), and infections (CMV, n = 3; BKvirus, n = 1; sepsis, n = 1). One patient developed limited chronic GVHD of skin and mouth. All patients engrafted, with predominantly donor chimerism. One patient had loss of chimerism 8 months after HSCT and was successfully submitted to a second transplant with the same sibling donor. One patient died 50 days after transplant of sepsis. Eight patients are alive and well, at a median follow-up of 19 (range 4-57) months post-transplantation. Conclusion: Allogeneic HSCT with reduced toxicity regimen is a good alternative in the treatment of patients with CGD. These good results may expand the indications of transplant in this disease, including patients with less severe complications pre HSCT.