Hodgkin lymphoma (HL) is the most common form of lymphoma affecting young people under the age of 30 in the Western world. Despite remarkable therapeutic advances over the past half century, 25% of people with this disease relapse after treatment. The majority of these individuals receive further treatment, consisting of both chemotherapy and bone marrow transplantation ("second-line treatment"). The survival rate of such relapse treatments is about 50%. The tumors in HL contain rare malignant cancer cells (Hodgkin Reed Sternberg cells) and the so-called "tumor microenvironment" is mainly made up of immune cells which are attracted and manipulated by the malignant cells. We have recently shown that features of the tumor, mainly related to the makeup of the microenvironment, can be used to predict whether the first treatment of the HL will cure the patient. However, our knowledge about the biology of relapsed HL is rudimentary at best and currently there are no tumor markers that allow us to predict whether second-line treatment will cure a patient who has relapsed. We have access to tumor samples from both the time of diagnosis and lymphoma relapse from 147 HL patients who received treatment. We will examine these pairs of biopsies to determine differences in both the cancer cells and the microenvironment using microscopy, special stains and expression of genes. We will use this information to build a tool to predict whether second-line treatment will cure a patient after they have relapsed. Our work will inform these patients and their doctors about likely outcomes of treatment and will also identify patients who might respond better to other treatment options. These studies will provide a greater understanding of why patients with HL relapse to potentially develop new treatments to cure HL relapse patients.