In general, the use of combined chemotherapy and low-dose involved-field radiation therapy (LD-IFRT) broadens the spectrum of potential toxicities, while reducing the severity of individual drug-related or radiation-related toxicities. Current approaches use chemotherapy with or without LD-IFRT. The volume of radiation and the intensity/duration of chemotherapy are determined by prognostic factors at presentation, including presence of constitutional symptoms, disease stage, and bulk.
Devising the ideal therapeutic approach for children with Hodgkin lymphoma is complicated by their risk for late adverse effects. In particular, radiation therapy doses used in adults can cause profound musculoskeletal growth retardation and increase the risk for cardiovascular disease  and secondary solid malignancies in children. Further complicating the treatment of children are gender-specific differences in chemotherapy-induced gonadal injury. The desire to cure young children with minimal side effects has stimulated attempts to reduce the intensity of chemotherapy (particularly alkylating agents) and radiation dose and volume. Because of differences in age-related child developmental status and the gender-related sensitivity to chemotherapy toxicity, no single treatment approach is ideal for all pediatric and young adult patients.
Pediatric oncologists agree that standard-dose radiation therapy, particularly applied to large volumes including critical organs, such as the mantle field, has unacceptable toxicity, including growth disturbance in prepubertal children, increased risk for breast cancer in young females, and cardiovascular complications. Therefore, all children and adolescents treated in pediatric cancer centers generally receive combination chemotherapy as initial treatment. Intensity and duration of initial chemotherapy is generally based on stage, the presence or absence of symptoms at diagnosis, and the presence or absence of bulk disease.[4,5,6]
The general treatment strategy that is used to treat children and adolescents with Hodgkin lymphoma is chemotherapy for all patients, with or without radiation. An exception to this general approach is selected patients with stage I, completely resected, nodular lymphocyte-predominant Hodgkin lymphoma, whose initial treatment may be surgery alone. The number of cycles and intensity of chemotherapy may be determined by the rapidity and degree of response, as is the radiation dose and volume.
Chemotherapy for Childhood/Adolescent Hodgkin Lymphoma
Drugs utilized as frontline therapy for children and adolescents with Hodgkin lymphoma include:
When regimens containing alkylating agents were shown to be associated with an increased risk for therapy-related leukemia, nonalkylator-containing regimens such as ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) were developed. Doxorubicin, however, is associated with cardiac damage and bleomycin can produce pulmonary fibrosis. Hybrid regimens that utilized lower total cumulative doses of alkylators, doxorubicin, and bleomycin were then developed. The COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, and vinblastine) hybrid is an example of this type of regimen. In an effort to decrease risk for male infertility, etoposide has been substituted for procarbazine in the initial courses of therapy in studies of the German pediatric Hodgkin lymphoma group and dacarbazine for procarbazine in subsequent courses.; [Level of evidence: 2A] In the GPOH-HD-2002 study, the 5-year overall survival (OS) was 97% and event-free survival (EFS) was 89%, with no difference in outcome between boys and girls. ABVE (doxorubicin [Adriamycin], bleomycin, vincristine, and etoposide) and ABVE-PC (prednisone and cyclophosphamide) have been used in Pediatric Oncology Group (POG) trials.; [Level of evidence: 1iiDi] Although etoposide is associated with an increased risk for therapy-related acute myeloid leukemia (AML) with 11q23 abnormalities, the risk is very low in those treated with ABVE or ABVE-PC without dexrazoxane. Procarbazine is no longer used in frontline Hodgkin lymphoma trials by the Children's Oncology Group (COG) due to its long-term gonadal toxicity in males.