RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy also work in different ways to kill more cancer cells or stop them from growing. It is not yet known whether rituximab is more effective with combination chemotherapy or bendamustine hydrochloride in treating patients with mantle cell lymphoma undergoing peripheral blood stem cell transplantation.

PURPOSE: This randomized phase II trial studies how well giving rituximab together with combination chemotherapy or bendamustine hydrochloride followed by consolidation chemotherapy and peripheral blood stem cell transplantation works in treating older patients with previously untreated mantle cell lymphoma.

OBJECTIVES:

• To estimate the 2-year progression-free survival (PFS) of patients with newly diagnosed mantle cell lymphoma (MCL) treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone (RHCVAD), methotrexate and cytarabine (MTX/Ara-C), and autologous stem cell transplant (ASCT) or rituximab and bendamustine (R-bendamustine) and autologous stem cell transplant and to select a regimen for further development.
• To assess the response rate and overall survival of patients with newly diagnosed MCL treated with R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT.
• To assess the toxicity and tolerability of R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT in patients with newly diagnosed MCL.
• To determine the prognostic value of quantitative minimal-residual disease (MRD) monitoring in the peripheral blood of MCL patients after induction therapy and serially after high-dose chemotherapy and ASCT on treatment outcome.
• To bank diagnostic tissue sections for future translational research studies.

OUTLINE: This is a multicenter study. Patients are stratified according to risk classification by Mantle Cell Lymphoma International prognostic Index (MIPI) score (low risk vs intermediate/high risk). Patients are randomized to 1 of 2 treatment arms.

• Arm I (induction therapy):

  • Courses 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2.
  • Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of course 2.
  • Each course is 21 days long and continues in the absence of disease progression or unacceptable toxicity.

• Arm II (induction therapy):

  • Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks later, patients with responsive disease receive 2 additional courses of treatment.
  • Stem cell mobilization: Beginning within 8 weeks, patients receive rituximab IV and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell collection about 26 days later.

Consolidation therapy: Patients receive one of the following preparative regimens.

• BCV* chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2.
• BEAM* chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1.
• TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2.
• NOTE: * Patients 61 years of age or older receive either BCV or BEAM.
• NOTE: * *TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 8 years from registration.

DISEASE CHARACTERISTICS:

• All patients must have previously untreated stage III, IV, or bulky stage II mantle cell lymphoma (MCL)

  • A diagnosis of MCL must be confirmed by histopathological diagnosis including immunohistochemistry and flow cytometry documenting both of the following phenotypes:

    • CD19+ or CD20+
    • Cyclin D1+ or evidence of the t(11;14) translocation by cytogenetics or FISH

• Adequate sections from the original diagnostic specimen must be available for submission for central review

  • An adequate biopsy requires sufficient tissue to establish the architecture and a WHO histologic subtype with certainty

    • Core biopsies, especially multiple core biopsies, MAY be adequate, but needle aspirations or cytologies are not adequate

  • Bone marrow core biopsy or clot sections (not aspirates) may be used as diagnostic material if it is significantly involved and are the only diagnostic material available

• All patients must have bidimensional measurable disease documented on the Lymphoma Baseline Tumor Assessment Form (Form #48031)

  • Patients who also have non-measurable disease in addition to measurable disease must have all nonmeasurable disease assessed within 28 days prior to registration

• Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma

  • Any laboratory or radiographic tests performed prior to registration to assess CNS involvement must be negative

• Patients must have a unilateral/bilateral bone marrow aspirate and biopsy for staging performed within 42 days prior to registration

  • If the biopsy cannot be performed but the aspirate is unequivocally consistent with mantle cell lymphoma, this will be considered adequate for staging purposes

• Patients must be eligible for stem cell transplantation by institutional guidelines with the plan that transplant will be conducted at a cooperative group-approved transplant center

  • Patients must be planning to undergo stem cell transplantation within 84 days after day 1 of the last induction course
  • Patients must have had at least 1.5 X 10^6 CD34^+ cells/kg collected and stored prior to second registration for stem cell transplantation

PATIENT CHARACTERISTICS:

• Zubrod performance status of 0-2

• Bilirubin ≤ 3 times upper limit of normal (ULN)

• Serum creatinine ≤ 2.0 times ULN

• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Platelet count ≥ 100,000/mcL, unless due to bone marrow infiltration by lymphoma

• All patients ≥ 45 years of age must have an echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA )scan within 42 days prior to registration (whichever method is used at baseline must be used at restaging)

  • Patients < 45 years of age should have ECHO/MUGA only if clinically indicated
  • Patients with an ejection fraction < institutional lower limit of normal (ILLN) are not eligible

• Serum Lactate dehydrogenase (LDH) and a Complete Blood Count (CBC with differential must be measured within 28 days prior to registration

• Patients known to be HIV positive, or who have a history of solid organ transplantation, are ineligible

• No active hepatitis

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated Stage I or II cancer from which the patient is currently in complete remission; or any other cancer from which the patient has been disease-free for 5 years

• Pregnant or nursing women may not participate

• Women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics