The impact of secondary hypogammaglobulinaemia in children with acute lymphoblastic leukaemia receiving maintenance chemotherapy

Hypogammaglobulinaemia is a potential complication in children with acute lymphoblastic leukaemia (ALL) receiving chemotherapy. However, real-world data on its prevalence and clinical impact remain limited. This study retrospectively reviewed 85 paediatric ALL patients completing Taiwan Pediatric Oncology Group (TPOG)-ALL-2013 maintenance therapy to investigate secondary hypogammaglobulinaemia. At diagnosis, 6% (5/85) of patients had hypogammaglobulinaemia, increasing to 49.2% (32/65) during maintenance chemotherapy. Patients with very-high-risk disease, poor cytogenetics or baseline immunoglobulin G (IgG) <1000 mg/dL were more likely to develop secondary hypogammaglobulinaemia. Febrile episodes were significantly more common in the hypogammaglobulinaemia group (40.6% had >10 fever episodes) and were particularly frequent in patients with IgG <400 mg/dL. However, hypogammaglobulinaemia was not associated with white blood cell count, measurable residual disease or long-term survival outcomes. Although intravenous immunoglobulin (IVIG) replacement is well established in primary immunodeficiency and B-cell malignancies, its role in paediatric ALL remains uncertain. Given the high prevalence of hypogammaglobulinaemia and its association with febrile episodes, routine IgG monitoring may help identify at-risk patients. Further studies are needed to determine the clinical benefits of IVIG supplementation in this population.