Duas décadas de experiência em imunodeficiência combinada grave (SCID) em um centro de referência brasileiro

• Ano de defesa: 2024
• Autor(a) principal: Gabriela Assunção Goebel
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; MEDICINA - FACULDADE DE MEDICINA; Programa de Pós-Graduação em Ciências da Saúde - Saúde da Criança e do Adolescente; UFMG
• Palavras-chave em Português: Imunodeficiência Combinada Grave; SCID; Infecções; Triagem neonatal; TREC; Transplante de células tronco hematopoiéticas; Imunodeficiência Combinada Severa; Mortalidade; Mycobacterium bovis; Transplante de Medula Óssea; Dissertação Acadêmica
• Link de acesso: http://hdl.handle.net/1843/77565

Severe combined immunodeficiency (SCID) is a heterogeneous genetic disorder characterized by severe T-cell lymphopenia with a profound impairment of T and B cell function and, in some types, also of NK cells. Although the majority of patients appear healthy at birth, affected babies present with severe infections and high mortality rates in early infancy. For this reason, SCID is considered a pediatric emergency. Increasing knowledge about the disease is essential for the optimal management of these patients until curative treatment with hematopoietic stem cell transplantation (HSCT), the only treatment currently available in Brazil. This report aims to describe the demographic, phenotypic and genotypic profile of patients diagnosed with SCID followed up at a Brazilian reference center and to correlate early diagnosis and therapy with the clinical evolution and survival of these patients. Medical records of 20 patients diagnosed with SCID over the last two decades were analyzed (including typical SCID, leaky-SCID and Omenn Syndrome). Data was collected between November 2021 and July 2023. Sixteen children were male (80%) and four female (20%). The median age at diagnosis was 164 days (ranging from 18 to 633 days). Patients were separated into two distinct groups: with early diagnosis at birth, n=7, from a pilot newborn screening program for SCID or with positive family history, and another group with late diagnosis by clinical presentation, n=13. Of the thirteen patients diagnosed late, five had very severe infections at diagnosis and died within a few months. Of the remaining eight patients, one had lost follow-up, one died while awaiting HSCT, and the other six were transplanted. The 2-year overall survival (OS) of this group was 29,2%, in contrast to the 2-year OS of the early diagnosis group, which was 71,4% (p = 0.053). All seven patients with an early diagnosis underwent HSCT. The survival rate after HSCT was similar between the two groups (p = 0.77). Between 2020 and 2021, there was an increase in the number of SCID diagnoses at this referral center (n=7), coinciding with the start of a newborn screening pilot program. As a result, more children were diagnosed and had the opportunity to get treatment before potentially fatal infections. However, the delay between diagnosis and curative treatment with HSCT in both groups was similar, with a median of 11 months. As well documented in the literature, this delay is one of the main factors that directly influence the survival of these children. As a result, in this study, there was no difference 11 in survival after HSCT between the two groups. With the official implementation of neonatal screening, we hope that, in addition to early diagnosis, a national flow can be organized to ensure that these patients receive curative treatment by 3.5 months of age and before the onset of symptoms, which could significantly reduce the morbidity and mortality of the disease in Brazil.