Subjects have a type of cancer called Hodgkin Disease (HD), a cancer of the lymph system. The lymph system is made up of tissue throughout the body that makes and stores infection-fighting cells. HD is one of the most treatable childhood cancers. The standard treatment for HD involves chemotherapy (treatment with anti-cancer drugs) and radiation therapy (the use of high-dose x-rays to get rid of cancer cells). Although they are cured from their cancer, some patients experience negative side effects from treatment later in life. These kinds of side effects are often referred to as late effects. This can include problems with growth, problems with some organ functions, and sometimes second cancers. These types of effects can be associated with either chemotherapy or radiation therapy. The investigators are therefore designing studies to minimize or prevent these late effects. It is thought that if some patients can be successfully treated without radiation, those patients might experience fewer late side effects.

Some patients, however, do not respond as well to the first stages of treatment (slow early responders). Slow early responders are considered to be at higher risk for relapse. This study also looks at whether these kinds of patients will benefit from additional chemotherapy.

The purpose of this study is to look at how the immune system recovers and at how certain T-cells in the blood behave after receiving chemotherapy with or without radiation. The investigators also want to identify if bio-markers (special proteins in blood and in cancer) relate to the response of HD to study treatment.

At first the subject will have 2 cycles of cancer drugs (Doxorubicin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide). The doctors call this combination of cancer drugs ABVE-PC for short. A cycle equals 21 days. The cancer drugs will be given intravenously (IV).

Those patients evaluated as having an early response to treatment will be put in the group of Rapid Early Responders (RERs). The RER group includes those patients whose disease has been reduced by 60% or more. The next step for patients with RERs is 2 more cycles of ABVE-PC chemotherapy followed by another evaluation of their response. Those determined to have a complete response (at least an 80% disease reduction) will receive no further therapy. Those patients determined to have less than a complete response will receive radiation therapy within 6 weeks after the last cycle or when blood counts are recovered. Radiation therapy will be given to the involved areas and by the standard of care of this hospital (Texas Children's Hospital). After radiation the subject will be off treatment.

Patients with disease reduction less than 60% are put in the group of Slow Early Responders (SERs). The next step for patients with SER is 2 cycles of DECA (Dexamethasone, Etoposide, Cytarabine, and Cisplatin). On Days 1 and 2, the subject will be given dexamethasone IV first; afterwards, then they will receive the Etoposide and Cytarabine mixture. Cisplatin will be given by IV only on Day 1.

BIOLOGY TESTS The doctors are investigating molecules in tumors and blood that may help them better understand the biology of Hodgkin's Disease. These studies may also help them understand differences in patients' responses to therapy.

TISSUE FOR BIOMARKER STUDIES The doctors want to study the material that shows the make-up of the cancer (the genes of the cancer tissue) and the special "markers" of the tissue. Tissue from the subject's cancer biopsies will be used for these studies. They will collect these samples when the subject has a biopsy for clinical reasons.

IMMUNE FUNCTION AND BIOMARKER BLOOD TESTS The doctors also want to collect blood samples to study the subject's immune system and to look at biomarkers in the blood.

Inclusion Criteria:

Patients with newly diagnosed, histologically confirmed Hodgkin Lymphoma (HD) who meet the following criteria:

• Stage IA and IB (non-bulky nodular lymphocyte predominant)
• Stage IIA and IIB
• Stage IIIA
• Stage IVA

Exclusion Criteria:

• Patients with Stage IA-IIA non-bulky lymphocyte predominant histology
• Patients who have received previous chemotherapy or radiation therapy (does NOT include steroids).
• Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction <27%).
• Patients with severe renal disease (i.e. Measured or estimated creatinine clearance or radioisotope GFR <= 70 ml/min/1.73 m2).
• Patients with pre-existing severe restrictive pulmonary disease (FVC less than 60% of predicted).
• Patients with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST greater than 500 IU/L).
• Known HIV positivity
• Patients with a Karnofsky performance score <70% or Lansky score <70%.
• Female patients who are pregnant or breast feeding.