It has been over 44 years since I began my fellowship in pediatric hematology and oncology. When I decided to enter this area of pediatrics, friends and family asked how I could possibly want to work with children with such dire prognoses and serious diseases. Despite the poorer survival of children with cancer when I began my journey, dramatic improvement in survival and cures has been seen in the decades that followed. In particular, the pediatric lymphomas reviewed in the February 2024 issue of Pediatrics in Review by Catueno and Cuglievan have seen overall five-year survival improve from 72.9% for the time period 1975-1979 to 94.2% in 2010-2019, based on results from the Surveillance, Epidemiology, and End Results Program (SEER) of the National Cancer Institute.
Looking at specific subsets of pediatric lymphoma Hodgkin Disease, already with a 5-year survival overall of 86% in 1975-1979, improved to greater than 97% in 2010-2019, and most remarkedly Burkitt Lymphoma has improved from 35% overall survival in the earlier period to greater than 90% the last time this was analyzed. These advancements are a result of developing an organized approach to treatment through multi-institutional cooperative group studies as developed in the US by the Pediatric Oncology Group and its legacy partners, improvements in therapies, including the use of risk adaptive therapies that deliver more intensive treatments to children with higher risk disease, and therapies targeted at specific molecular or cellular signatures of the malignant cells. In the February article, Catueno and Cuglievan present a logical approach to the many histologic variants of Hodgkin and non-Hodgkin lymphoma, describe the epidemiology, biology, presentation, staging, diagnostic evaluations necessary, possible emergent situations, treatment, and the need to be aware of the late effects of therapy for this diverse group of malignancies.
What, however, are the key issues and take-home points for the general pediatrician? In my mind the most important thing is suspicion. Lymphoma is a rare diagnosis with 3-4 new patients per 100,000 children per year in patients younger than 20 years of age. Pediatricians are continually seeing patients with fever and lymphadenopathy in their day-to-day practice. Most of these patients will have nonmalignant causes for their adenopathy and fever, as outlined in Lymphadenopathy: Differential Diagnosis and Indications for Evaluation by Stanford et al. in the August 2024 issue of Pediatrics in Review. Persistence of enlarged non-tender lymph nodes or the other warning signs discussed in the February 2025 article should lead to further diagnostic evaluation of complete blood count, possibly a chest radiograph, and basic laboratory studies and assessment for the presence of oncologic emergencies. Then, early referral to the subspecialist is appropriate. If a diagnosis of lymphoma is made the treatment will be determined by the specialist, and the pediatrician’s role becomes one of providing support and hope to the family and continued care of the siblings.
The history of cancer therapy in children is one of incremental changes to improve survival while limiting short- and long-term complications. In more recent years, the use of targeted therapies has strived to continue this improvement by developing therapies that are aimed at a specific molecular defect instrumental in the development of cancer, or a specific marker on the surface of the cancer cell. Examples of these, as mentioned by Catueno and Cuglievan, are rituximab in the treatment of Burkitt lymphoma and the use of Anti-CD 30 in the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma. The hope of targeted therapy is improvement in cure with more limited side effects compared to standard chemo and radiation therapy.
Given improvements in survival, the pediatrician will likely resume care of the patient after the completion of therapy and short-term follow-up. The pediatrician must become aware of the specific chemo-radiation therapy and targeted therapies given. The pediatrician becomes a member of the long-term survival team, monitoring for late effects of the disease and treatment, as outlined by the COG Long-term Survivor guidelines (www.survivorshipguidelines.org). Finally, it becomes the pediatrician's job to transition the patient to adult care and ensure that future care providers understand the specific needs of the patient and family.
Despite the improved survival, a pediatric lymphoma diagnosis is devastating for the patient and family involved. It is common for the general pediatrician to also feel a sense of loss. Remembering the improvements in survival and the needs of the patient for the future will help you support the patient, family, and yourself.
