Prognostic Factors in Childhood and Adolescent Hodgkin Lymphoma
As the treatment of Hodgkin lymphoma has improved, factors that influence outcome have diminished in importance. Several factors, however, continue to influence the success and choice of therapy. These factors are interrelated in the sense that disease stage, bulk, and biologic aggressiveness are frequently codependent. Further complicating the identification of prognostic factors are their use in determining the aggressiveness of therapy. For example, in a report from the German-Austrian Pediatric multicenter trial DAL-HD-90, bulk disease was not a prognostic factor for outcome on multivariate analysis. However, in this study boost irradiation doses were given to patients who had postchemotherapy residual disease, which could have obfuscated the relevance of bulky disease at presentation. This underscores the complexity in determining prognostic factors.
Pretreatment factors associated with an adverse outcome in one or more studies include advanced stage of disease, the presence of B symptoms, the presence of bulk disease, extranodal extension, male sex, and elevated erythrocyte sedimentation rate. One study showed that African American patients had a higher relapse rate than Caucasian patients, but overall survival was similar. Examples from selected multi-institutional studies are discussed here. In the Society for Paediatric Oncology and Haematology (GPOH) GPOH-95 study, B symptoms, histology, and male sex were adverse prognostic factors for event-free survival on multivariate analysis. In 320 children with clinically staged Hodgkin lymphoma treated in the Stanford-St. Jude-Dana Farber Cancer Institute consortium, male gender; stage IIB, IIIB, or IV disease; white blood cell count 11,500/mm� or higher; and hemoglobin lower than 11.0g/dL were significant prognostic factors for inferior disease-free survival and overall survival. Prognosis was also associated with the number of adverse factors. In the CCG-5942 study, the combination of B symptoms and bulky disease was associated with an inferior outcome.
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.
There is some controversy as to whether histology is an important prognostic factor. Serum markers that have been associated with an adverse outcome include soluble vascular cell adhesion molecule-1, tumor necrosis factor, soluble CD30, beta-2 microglobulin, transferrin, and serum IL-10 level. High levels of caspase 3 in Reed-Sternberg cells have been associated with a favorable outcome.
The rapidity of response to initial cycles of chemotherapy also appears to be prognostically important and is being used in the research setting to determine subsequent therapy.[13,14,15] Positron emission tomography (PET) scanning is being evaluated as a method to assess early response in pediatric Hodgkin lymphoma. Fluorodeoxyglucose-PET avidity after two cycles of chemotherapy for Hodgkin lymphoma in adults has been shown to predict treatment failure and progression-free survival.[16,17,18] Further studies are required to assess the magnitude of the prognostic effect with different chemotherapy regimens and to determine whether improved outcome can be achieved by altering the therapeutic strategy based on early PET response.