Clinical Features Before Hematopoietic Stem Cell Transplantation or Enzyme Replacement Therapy of Children With Combined Immunodeficiency

Background: Survival of children with combined immunodeficiency is strongly related to patient's age and clinical situation at the time of hematopoietic stem cell transplantation (HSCT). We describe the clinical features before HSCT or enzyme replacement therapy (ERT) in a cohort of children treated in a National Reference Unit. Methods: A retrospective study of children with CIDs treated in our Hospital during a 20-year period (1995-2014) was performed, analyzing their clinical situation before HSCT/ERT. Results: Thirty-one children were included. Risk factors such as family history or consanguinity were present in 35% of cases, but only 3 children (9%) were initially studied because of family history. Median ages at clinical onset, diagnosis and HSCT/ERT were 3.3, 5.6 and 8.1 months, respectively. All patients had lymphopenia before HSCT/ERT. At the time of admission to our unit, 68% of cases had abnormal lung auscultation, 72% were malnourished, 45% reported chronic gastroenteritis and 35% had hepatosplenomegaly. Before HSCT/ERT, respiratory infections and sepsis episodes were documented in 80% and 42% of cases, respectively. In 23% of children, a viral systemic infection was confirmed. The mortality rate was 35%, and 72% of children who died had Gram-negative bacterial sepsis or a viral infection. Conclusions: The present study shows the characteristics and outcome of children with CIDs in the absence of neonatal screening. Although all our patients had lymphopenia and most of them had suffered relevant infections or had a positive family history, these factors were not identified early. Respiratory and systemic viral infections were the main source of infection with important implications in clinical outcome. Our results highlight the importance of the implementation of neonatal screening, to improve survival rates.