Hematopoietic stem cell transplantation in children with non-malignant disorders

Hematopoietic Stem Cell Transplantation (HSCT) is a curative option for specific non-malignant disorders in childhood, including hemoglobinopathies and primary immune deficiencies. Despite promising results in the recent years, many issues regarding timing of HSCT, donor selection, conditioning regimen and post-transplant care are currently open. Here, a cohort of 11 patients with Sickle Cell Disease transplanted after a Treosulfan-based conditioning regimen is described showing that this approach is suitable also when alternative donors are employed. Optimal modalities for HSCT in patients with Hemophagocytic Lymphohistiocytosis (HLH) are investigated through the analysis of outcomes of a 109 transplanted children. We demonstrate that active HLH should not preclude transplantation and that haploidentical HSCT is associated with dismal outcomes. Finally, data regarding supportive measure and psychological consequences of HSCT in children are presented

Robot-assisted splenectomy in a teenager with chronic autoimmune thrombocytopenia

The use of the Da Vinci Xi system is gaining popularity among all surgical disciplines. A splenectomy is a treatment option for patients with hematological disorders and splenic lesions. The laparoscopic approach is nowadays the standard of care. Despite the initial controversy, recently it has been demonstrated the superiority of robotic splenectomy performed in ''difficult'' cases. We report, to our knowledge, the first case of robot-assisted splenectomy following embolization of the splenic artery in a 15-year-old patient with chronic immune thrombocytopenia, worsened by a severe cerebral sinus thrombosis, while being treated with eltrombopag and mycophenolate. Due to the need for a rapid rise in platelet counts and failure of several medical treatments, splenectomy was advocated. To raise the platelet count pre-operatively and minimize intraoperative bleeding, the embolization of the spleen artery was performed before the planned splenectomy. The intervention was carried on without any complication and at 1 year follow up the patient is in good clinical condition and has improved his neurological condition. We propose a robotic splenectomy following embolization of the splenic artery as a feasible and safe procedure. The advantages of the Da Vinci Xi system are highlighted especially in complex cases, requiring maximum precision

Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience

Abstract To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P  = .030) and second or third HSCT ( P  = .018). Characteristics significantly associated with mortality were mismatched HSCT ( P  = .011), relapse of underlying disease before PICU admission ( P P  = .012), hepatic failure at admission ( P  = .021), and need for invasive ventilation during PICU course (

Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease

CARMIL2 is required for CD28-mediated co-stimulation of NF-kappa B signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelic CARMIL2 variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the same CARMIL2 null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missense CARMIL2 variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations. CARMIL2 should be included in the diagnostic work-up of patients with suspected monogenic IBD

Impact of newborn screening for SCID on the management of congenital athymia

BACKGROUND: Newborn screening (NBS) programmes for severe combined immunodeficiency (SCID) facilitate early SCID diagnosis and promote early treatment with haematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS due to severe T-cell lymphopaenia. With the expanding introduction of NBS programmes, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH), London, United Kingdom. OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared the age at referral and complications between athymic infants diagnosed after clinical presentation (N=25) and patients identified through NBS (N=19), referred for thymus transplantation at GOSH between 10/2019 and 02/2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: Infants referred after NBS identification were significantly younger and had less complications, in particular less infections. All deaths occurred in the non-NBS group, including six patients before and two after thymus transplantation because of pre-existing infections. In the absence of significant co-morbidities or diagnostic uncertainties, timely treatment was more frequently achieved after NBS. Treatment at <4 months of age was associated with higher thymic output at 6- and 12-months post-transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation prior to acquiring infections or other complications, and facilitating treatment at younger age, thus playing an important role in improving their outcomes

Impact of newborn screening for SCID on the management of congenital athymia

Background Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). Objective We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. Methods We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. Results The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. Conclusion NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes

Hematopoietic stem cell transplantation in children with non-malignant disorders

Hematopoietic Stem Cell Transplantation (HSCT) is a curative option for specific non-malignant disorders in childhood, including hemoglobinopathies and primary immune deficiencies. Despite promising results in the recent years, many issues regarding timing of HSCT, donor selection, conditioning regimen and post-transplant care are currently open. Here, a cohort of 11 patients with Sickle Cell Disease transplanted after a Treosulfan-based conditioning regimen is described showing that this approach is suitable also when alternative donors are employed. Optimal modalities for HSCT in patients with Hemophagocytic Lymphohistiocytosis (HLH) are investigated through the analysis of outcomes of a 109 transplanted children. We demonstrate that active HLH should not preclude transplantation and that haploidentical HSCT is associated with dismal outcomes. Finally, data regarding supportive measure and psychological consequences of HSCT in children are presented.Il trapianto di cellule staminali ematopoietiche (TCSE) è un trattamento curativo per specifiche patologie non oncologiche in età pediatrica, tra cui le immunodeficienze primitive e le emoglobinopatie. Negli ultimi anni, sono stati ottenuti risultati promettenti, ma non è ancora chiaramente definito in quale fase di malattia debba essere effettuato il TCSE, come selezionare il donatore, quale regime di condizionamento e quale terapia di supporto sia più efficace. In questo lavoro, è stata descritta una coorte di 11 pazienti con Drepanocitosi trapiantati impiegando un regime di condizionamento basato sul Treosulfano, dimostrando ottimi risultati anche con l’impiego di donatori alternativi. Sono state analizzate le modalità ottimali del TCSE per pazienti con Linfoistiocitosi Emofagocitica valutando una coorte di 109 pazienti trapiantati in Italia. È stato dimostrato che la malattia attiva al momento del trapianto non preclude il TCSE mentre il trapianto aploidentico è un fattore prognostico sfavorevole. Infine, vengono presentati dati riguardanti le terapie di supporto e le conseguenze psicologiche a lungo termine del TCSE in età pediatrica