Dose Adjusted EPOCH-R, to Treat Mature B Cell Malignancies

The subject will need to have a variety of tests, exams, or procedures to find out if s/he
can be on the study.

The subject will also require placement of a catheter that stays in the vein for safe
administration of chemotherapy drugs.

During the study...

If all of the tests that have been done show that s/he can participate and s/he chooses to
participate, treatment cycles will begin.

A cycle equals three weeks. The subject will have a minimum of 6 cycles of treatment,
possibly 8. The cancer drugs s/he will receive are etoposide, vincristine, doxorubicin,
cyclophosphamide, prednisone, and rituximab with each cycle. The amount of the drugs will be
determined by the subject's weight at first, and some of the drugs will be adjusted up or
down for later cycles.

Rituximab will be given on Day 1 prior to continuous infusion drugs.

After 4 cycles, the subject will have imaging scans again to see how the cancer responded to
treatment. If the cancer responds completely after 4 cycles, s/he will get 2 more cycles (6
cycles total). If the cancer partially responds, s/he will get 4 more cycles (8 total
cycles).

If the subject has cancer in the Central Nervous System, s/he will receive a drug called
methotrexate. If s/he does not have cancer in the CNS, s/he will get methotrexate to try to
prevent CNS cancer.

Inclusion Criteria:

- Patient with newly diagnosed, histologically confirmed, Group B or C diffuse large
B-cell lymphoma; or primary mediastinal B-cell lymphoma. Patients with Group B/C post
transplant lymphoproliferative disorder are eligible for the study regardless of
whether disease is newly diagnosed. (Murphy staging will be used for group
classification.)

Exclusion Criteria:

- Patient who has received previous chemotherapy or radiation therapy in the previous 3
months, except for empiric initial intrathecal administration at diagnosis. Rituximab
or steroid administration is not an exclusion criterion.

- Patient who has received any prior anthracyclines.

- Patient with symptomatic cardiac failure unrelieved by medical therapy or evidence of
significant cardiac dysfunction by echocardiogram (shortening fraction <28%) NOT due
to mediastinal mass.

- Patient with severe renal disease (i.e. creatinine greater than 3 times normal for
age; creatinine clearance less than 50 ml/min/1.73m2).

- Patient with severe hepatic disease (direct bilirubin greater than 3 mg/dl or AST
greater than 500 IU/L).

- Patient with a Karnofsky performance score <50% or Lansky score <50%.

- HIV-positive patients will be excluded unless antiretroviral therapy can be safely
withheld during chemotherapy administration, based on clinical determination of
infectious disease team evaluation.

- Female patient who is pregnant or breastfeeding.

- Patient with reproductive potential not willing to use an acceptable method of birth
control (i.e. hormonal contraception, intrauterine device, condom or diaphragm with
spermicide, or abstinence) for the duration of the study and one year post completion
of therapy.

- Patient with primary central nervous system (CNS) lymphoma (lymphoma limited to the
craniospinal axis without systemic involvement)

- Patient with Burkitt cell lymphoma or leukemia.

- Patient with group classification A disease, or group classification B stage I or II
disease with normal LDH level AND tumor mass less than 7 cm.