RESUMEN
B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common childhood cancers worldwide. Although most cases are sporadic, some familial forms, inherited as autosomal dominant traits with incomplete penetrance, have been described over the last few years. Germline pathogenic variants in transcription factors such as PAX5, IKZF1, and ETV6 have been identified as causal in familial forms. The proband was a 7-year-old Mexican girl diagnosed with high-risk B-ALL at five years and 11 months of age. Family history showed that the proband's mother had high-risk B-ALL at 16 months of age. She received chemotherapy and was discharged at nine years of age without any evidence of recurrence of leukemia. The proband's father was outside the family nucleus, but no history of leukemia or cancer was present up to the last contact with the mother. We performed exome sequencing on the proband and the proband's mother and identified the PAX5 variant NM_016734.3:c.963del: p.(Ala322LeufsTer11), located in the transactivation domain of the PAX5 protein. The variant was classified as probably pathogenic according to the ACMG criteria. To the best of our knowledge, this is the first Mexican family with an inherited increased risk of childhood B-ALL caused by a novel germline pathogenic variant of PAX5. Identifying individuals with a hereditary predisposition to cancer is essential for modern oncological practice. Individuals at high risk of leukemia would benefit from hematopoietic stem cell transplantation, but family members carrying the pathogenic variant should be excluded as hematopoietic stem cell donors.
RESUMEN
Congenital Hemophilia A is a complex disease to treat, especially in places without access to hemophilia treatment centers (HTCs). The primary aim of this study was to analyze the outcomes of a cohort of adult people with congenital hemophilia A in an HTC localized in the Bajio region of Mexico. Observational retrospective study of a cohort of 82 adult people with congenital hemophilia A treated in a tertiary-level hospital in the Bajio region of Mexico, between June 2022 and June 2023. The median age of the patients was 29.5 years, 60.9% with severe hemophilia A, 53.6% were under some factor VIII prophylaxis regimen, and 52.4% had home therapy. The median annualized bleeding rate (ABR) was one bleed/year (IQR 0-3 bleeds/year) including a median of zero joint bleeds/year (IQR 0-3 bleeds/year). The presence of high-response inhibitors was detected in 8.5%, with an overall incidence of inhibitors of 14.6% of the cohort. Univariate analysis showed that inhibitors (OR 21.10; CI 95% 1.20-370.3; P = 0.03) and clinical arthropathy (OR 6.14; CI 95% 2.13-17.68; P = 0.001) were significantly higher in severe hemophilia. Clinically significant arthropathy was found in 71.9% of patients. Ultrasonography of the target joints showed that mainly cartilage degeneration was affected. Blood transfusion-associated viral infections were detected in 10.9% of patients. In our HTC, current treatment with hemostatic agents allows adequate control of ABR with acceptable inhibitor rates. However, we still have joint damage in most patients, which is partly explained by the fact that prophylaxis was introduced only in recent years.
RESUMEN
Abstract Introduction: Hemophagocytic syndrome, macrophage activation syndrome, reactive histiocytosis or hemophagocytic lymphohistiocytosis (HLH) represent a group of diseases whose common thread is reactive or neoplastic mononuclear phagocytic system cells and dendritic cell proliferation. Clinical case: We present a case of an HLH probably associated with Epstein-Barr virus (EBV) in a 4-year-old male patient treated with HLH-04 protocol. Viral etiology in HLH is well accepted. In this case, clinical picture of HLH was assumed secondary to EBV infection because IgM serology at the time of clinical presentation was the only positive factor in the viral panel. Conclusions: Diagnosis of HLH is the critical first step to successful treatment. The earlier it is identified, the less the tissue damage and reduced risk of multiple organ failure, which favors treatment response.
Resumen Introducción: El síndrome hemofagocítico, síndrome de activación de macrófagos, histiocitosis reactiva o linfohistiocitosis hemofagocítica (HLH) representan un grupo de enfermedades cuyo factor común es la proliferación reactiva o neoplásica de las células mononucleares fagocíticas y del sistema de células dendríticas. Caso clínico: Se presenta un caso de HLH sugestivo de tener una asociación con el virus del Epstein Barr (VEB) de un paciente masculino de 4 años de edad, tratado con el protocolo HLH-04. La etiología viral en HLH es reconocida. En este caso se asumió un cuadro de HLH secundario a una infección por VEB, ya que la serología de IgM en el momento de la presentación clínica fue la única positiva en el panel viral. Conclusiones: El diagnóstico de la HLH es el primer paso crítico para el éxito del tratamiento. Entre más temprano se identifique, existe menor daño tisular y menor riesgo de falla orgánica múltiple, lo que favorece la respuesta al tratamiento.