Causes of Mortality in Pediatric Hodgkin Lymphoma: Understanding the Risks and Complications

Hodgkin lymphoma is one of the most treatable forms of childhood cancer, particularly when diagnosed at an early stage. For pediatric patients with Stage I or II disease, the cure rate ranges between 80% and 90%, thanks to advances in chemotherapy, radiation therapy, and supportive care. However, despite high overall survival rates, certain complications—especially in cases of relapsed or refractory disease—can lead to life-threatening conditions. Understanding these risks is crucial for improving long-term outcomes and patient monitoring.

Advanced Disease and Bone Marrow Involvement

One of the most serious complications occurs when Hodgkin lymphoma progresses to Stage IV, characterized by widespread dissemination, including infiltration of the bone marrow. This advanced form, sometimes referred to as leukemic phase, disrupts normal hematopoiesis—the process of blood cell production. As a result, children may develop severe cytopenias: low platelet counts (thrombocytopenia), reduced red blood cells (anemia), and diminished white blood cells (leukopenia).

Thrombocytopenia increases the risk of uncontrolled bleeding, while leukopenia severely compromises the immune system, making patients highly susceptible to infections. Even common pathogens can lead to sepsis in immunocompromised children. Severe infections are among the leading causes of death in pediatric Hodgkin lymphoma, especially during intensive treatment phases or disease relapse.

Neurological Complications from CNS Involvement

Although rare, central nervous system (CNS) involvement is another critical factor contributing to mortality. When lymphoma cells infiltrate the brain or surrounding tissues, they can cause significant neurological damage.

Intracranial hemorrhage

In addition, tumor mass effect within the skull can elevate intracranial pressure, resulting in symptoms such as persistent headaches, vomiting, seizures, and altered mental status. Untreated or rapidly progressing cerebral edema can lead to herniation and death. Seizures caused by cortical irritation further complicate clinical management and may contribute to fatal outcomes if not promptly controlled.

Other Contributing Factors and Long-Term Risks

Beyond immediate disease progression, survivors of pediatric Hodgkin lymphoma face long-term health challenges due to treatment-related toxicity. While not directly causing early mortality, late effects such as secondary cancers, cardiovascular disease, and pulmonary dysfunction can impact overall survival years after remission. These underscore the importance of lifelong follow-up care and personalized survivorship plans.

Early detection, aggressive supportive care, and tailored therapies for high-risk or relapsed cases are essential to reducing mortality. Ongoing research into targeted therapies and immunotherapies offers hope for improving outcomes even in advanced-stage pediatric Hodgkin lymphoma.