Rituximab-HyperCVAD (R-HCVAD) Alternating With Rituximab-Methotrexate-Cytarabine- (R-MC) in Newly Diagnosed Patients With Diffuse Large B-Cell Lymphoma With MYC-Rearrangement.

Inclusion Criteria:

1. Diffuse large B-cell lymphoma or intermediate ("Burkitt-like") lymphoma, newly
diagnosed from an excisional biopsy or from a large core biopsy with sufficient
diagnostic material to perform genetic testing for MYC-R.

2. Positivity for MYC-R by Fluorescent in-situ Hybridization (FISH) or by classical
cytogenetics.

3. No prior lymphoma treatment, with one exception: One cycle of R-CHOP regimen is
permitted (consisting of one single dose each of Rituximab, of cyclophosphamide, of
doxorubicine, and of vincristine, as well as up to 5 doses of Prednisone when part of
chemotherapy).

4. No prior radiation therapy is permitted

5. Age ≥ 18 years to 70 years of age

6. CT imaging of neck, chest, abdomen and pelvis within 28 days prior to registration.
Any additional imaging used to assess extent of disease must also have been done
within 28 days prior to registration

7. Bidimensionally measurable disease by imaging within 28 days prior to registration

8. Adequate bone marrow biopsy, and aspiration performed for staging within 28 days
before registration, and before start of any treatment

9. Indication for primary treatment with systemic multiagent chemotherapy

10. Creatinine ≤ 2.0 mg/dL and estimated (Cockroft-Gault) creatinine clearance> 50 ml/min
within 7 days prior to registration

11. Cardiac ejection fraction of ≥ 50% by MUGA scan or by 2-D echocardiogram , as well as
EKG without significant abnormality within 28 days prior to registration

12. Performance status of 0, of 1, or of 2 (ECOG scale)

13. Patient willing to have, and to maintain, a central venous line throughout the
treatment phase (either PICC line, or double lumen tunnelled catheter, or double
lumen subcutaneous venous port system)

14. Willing and logistically able to be followed as outpatient at least twice weekly,
during the treatment phase.

15. Signed informed consent to accept transfusion of blood products as medically
indicated

16. Signed informed consent to participate in this trial

Exclusion Criteria:

1. Age > 70 years

2. Leukemic presentation, or no evidence of disease by imaging

3. Unwilling to be screened for HIV. HIV positive patients must receive combined
antiretroviral treatment while on study. They are excluded from participation unless
they show a CD4 count >250/uL and a viral load < 50 within 28 days of registration.

4. Hepatic involvement and total serum bilirubin ≥ 5 mg/dL within 7 days prior to
registration, or total serum bilirubin ≥ 1.6 mg/ dL without hepatic involvement
within 7 days prior to registration

5. Patients with bone marrow involvement and either ANC < 1000/uLor Platelets <
50,000/uL, within 7 days before registration

6. Patients without bone marrow involvement by lymphoma, and either ANC < 1500/uL or
Platelets < 100,000/uL within 7 days before registration

7. Patients with myelodysplastic syndrome, with sickle cell disease, or with transfusion
dependence for over 6 months antedating the diagnosis oflymphoma.

8. Known hypersensitivity to E. coli derived proteins

9. Patients at risk of reactivation of hepatitis B who are unwilling to be treated with
appropriate antivirals as medically indicated.

10. Pregnant or nursing women, or any patient with reproductive potential and unwilling
to use effective contraceptive method from study start to one year after the last
dose of protocol therapy. Adequate contraception is defined as hormonal birth
control, intrauterine device, double barrier method, or total abstinence.

11. Additional or prior malignancy except adequately treated basal cell or squamous cell
skin cancer, in situ cervical cancer, or other cancer for which the patient has been
disease-free for ~ 5 years

12. Unwilling to receive transfusions of blood products as medically indicated