Current approaches to the management of pediatric Hodgkin lymphoma

Hodgkin lymphoma is one of the few cancers that affect both adults and children. Cure rates for Hodgkin lymphoma remain among the best for pediatric cancers. However, cure is often associated with significant delayed effects of therapy, including an elevated risk for second malignancies, cardiotoxicity, pulmonary toxicity, and gonadal and non-gonadal endocrine dysfunction. Therefore, the aim of current treatment strategies is to further improve outcomes while minimizing therapy-related complications. At diagnosis, patients are classified into risk groups based on disease stage, and the presence of clinical, biologic, and serologic risk factors. In general, the most recent trials have intensified therapy in those patients with high-risk disease to improve disease control, and have limited therapy in those patients with low-risk disease to avoid secondary effects. In low-risk patients, multiple studies have been conducted to investigate limiting either radiation therapy or chemotherapy to prevent long-term side effects without affecting the excellent cure rate. In intermediate- and high-risk patients, many studies have examined intensifying therapy to improve event-free survival rates. In addition, response assessment by fluorine-18-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) may be particularly important in pediatric Hodgkin lymphoma; it may allow modification of treatment to maximize treatment efficacy and minimize late effects of chemotherapy and radiation therapy. Despite the improvements in treatment for all stages of Hodgkin lymphoma, there is still a subgroup of patients who do not enter remission with initial therapy or relapse after initial response to therapy. Unfortunately, standard-dose salvage chemotherapy for relapsed disease has disappointing results in terms of overall survival since patients have typically already received intensive therapy. While there is no standard of care in terms of salvage chemotherapy, high-dose chemotherapy with autologous stem cell transplant (ASCT) rescue has become the standard of care for the majority of children with relapsed Hodgkin lymphoma. The use of allogeneic transplantation is controversial in relapsed or refractory Hodgkin lymphoma; because of the high transplant-related mortality, allogeneic transplant has not been associated with improved overall survival over ASCT. As more has been learned about the biologic mechanisms involved in Hodgkin lymphoma, biologically-based therapies are being investigated for use in this disease, both at initial diagnosis and relapse. Both immunotherapy and small molecules are being studied as possible therapeutic agents in Hodgkin lymphoma. Unfortunately, the vast majority of investigations of novel agents have occurred exclusively in adult patients. However, since pediatric Hodgkin lymphoma and adult Hodgkin lymphoma are similar, these results may potentially be extrapolated to pediatric Hodgkin lymphoma.