Children with acquired hypocellular bone marrow failures of unknown cause (AHBMF) are usually diagnosed either as severe aplastic anaemia (SAA) or refractory cytopenia of Childhood (RCC). Patients with AHBMF who lack a matched donor and failed or relapsed after immunosuppressive therapy need alternative therapies. Haploidentical stem cell transplant (HAPLO) offers a curative treatment for these patients. To probe that HAPLO can be a successful therapy in paediatric patients with AHBMF and to assess therapy-related toxicity METHODOLOGY: A multicentre retrospective review of AHBMF treated with HAPLO. Eleven paediatric patients (SAA 9, RCC 2) were transplanted with HAPLO with different strategies of lymphodepletion (five post-transplant cyclophosphamide, two α/β CD19 depletion, and four CD45 RA depletion). Most patients (10/11) had failed to respond or relapsed after immunosuppressive therapy. The conditioning regimen was reduced intensity in SAA and myeloablative in RCC. Patients with SAA received low-dose radiotherapy as part of the conditioning regimen. All patients engrafted. Viral reactivation was common (8/11). Acute GVHD ≥ II was seen in 5 patients. Chronic GVHD was diagnosed in 4 of the long-term survivors. Transplant-associated microangiopathy was a frequent complication in SAA patients and was related to a worse outcome. Two patients died of transplant-related complications. Overall survival was 81%, with a median follow-up of 36 months. HAPLO was a successful salvage curative treatment for paediatric patients with AHBMF, but with significant toxicities that must be addressed. Transplant-associated microangiopathy was the most critical complication.

Introduction: The differential diagnosis of splenomegaly is a complex process that encompasses a wide variety of diseases. Moreover, it is not always standardized and lacks a definitive consensus on which tests should be performed and in what order. Gaucher disease (GD) and acid sphingomyelinase deficiency (ASMD) are lysosomal diseases (LD) that present with splenomegaly, the diagnosis of which requires a high index of suspicion and specific biochemical and genetic techniques. The aim of the project for the education and diagnosis of Gaucher disease and acid sphingomyelinase deficiency (PREDIGA) was to conduct educational training alongside an observational, multicenter, ambispective, cross-sectional, single-cohort study among patients having an enlarged spleen or undergone splenectomy to further assess these subjects to exclude two lysosomal diseases, namely GD and ASMD. Methods: Using dried blood spot (DBS) testing, we identified patients with abnormally low values of the enzymes glucocerebrosidase and acid sphingomyelinase, who then underwent sequencing of the GBA1 and SPMD1 genes, respectively. The study involved 34 hospitals and 52 medical specialists. Results: We identified 220 patients (208 adults and 12 children under 18 years) with cryptogenic splenomegaly or who had undergone splenectomy (12 patients) without having reached a diagnosis. The median age was 11 years (interquartile range [IQR] 3–16) in the pediatric population and 51 years (IQR 38–65) in the adult population. Lower-than-normal enzyme values were detected in 19 DBSs, confirming eight positive cases, which corresponded to six patients with GD and two with ASMD. The rest of the DBSs with low enzyme activity were not genetically confirmed (58%). We determined that lysosomal diseases accounted for 3.6% of cryptogenic splenomegaly/splenectomy cases in our setting: 2.7% were GD and 0.9% ASMD, in a ratio of 1 ASMD patient to every 3 GD patients. Lyso-GL1 values in patients with GD were elevated in all but one individual, corresponding to a child diagnosed at 4 months old. The variants detected in the GBA1 gene were consistent with the most frequent variants found in Spain. Discussion/Conclusion: The development and implementation of this protocol for the education and diagnosis of cryptogenic splenomegaly/splenectomy, even in asymptomatic patients, constitutes a comprehensive, simple, rapid, and effective screening method for the diagnosis of GD and ASMD.

Background: Pulmonary complications of transfusion are a leading cause of morbidity and mortality. Transfusion‐associated circulatory overload (TACO) is the most common, whereas transfusion‐related acute lung injury (TRALI) is less frequent but potentially fatal. Objective: To describe a pediatric case with overlapping features of TACO and TRALI following platelet transfusion and to highlight diagnostic and management challenges. Methods: We report the case of a 15‐year‐old patient with acute myeloid leukemia who developed acute respiratory compromise after platelet transfusion. Clinical findings, laboratory data (including pro‐BNP), imaging, and immunologic investigations were evaluated. Results: Elevated pro‐BNP levels and signs of fluid overload were consistent with TACO. However, chest radiography demonstrated non‐cardiogenic pulmonary edema, and pre‐existing pulmonary involvement supported a diagnosis of type II TRALI. Management included immediate cessation of transfusion, oxygen therapy, and comprehensive evaluation with cytokine profiling, antibody screening, and advanced immunologic testing. Conclusion: This case illustrates the diagnostic complexity of transfusion‐related pulmonary complications, particularly when TACO and TRALI features overlap, and underscores the importance of a multidisciplinary approach to management and investigation.

Las lesiones histiocíticas o histiocitosis se consideran neoplasias inflamatorias de origen mieloide, compuestas por células dendríticas o derivadas de macrófagos/monocitos de origen clonal, que infiltran tejidos y son causadas por alteraciones recurrentes que activan quinasas, con mayor frecuencia en las vías de señalización de la proteína quinasa activada por mitógenos (MAPK), PI3K-AKT y tirosina quinasa del receptor (RTK). La vía común conduce a la sobreexpresión de ERK y a la supervivencia celular. Los efectos devastadores de la histiocitosis se relacionan menos con su capacidad proliferativa y más con el daño tisular permanente y el daño fibroinflamatorio en sitios críticos (p. ej., hipófisis, cerebro, hígado), que ahora se sabe que están orquestados por células mediadoras inflamatorias tisulares. La histiocitosis de células de Langerhans es la forma más común en pediatría, con un amplio espectro de presentación clínica. El pronóstico habitualmente es bueno, pero, algunas veces, está condicionado por secuelas significativas. Las histiocitosis no Langerhans son menos frecuentes y también cubren un amplio grupo de entidades nosológicas. La linfohistiocitosis hemofagocítica no es una patología neoplásica histiocitaria, sino producto de la alteración de los mecanismos de regulación inmunológica.