Rituximab, Cyclophosphamide, and G-CSF Followed By Combination Chemotherapy in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant Followed By Rituximab and GM-CSF for Refractory Diffuse Large B-Cell Lymphoma

RATIONALE: Giving colony-stimulating factors, such as G-CSF, monoclonal antibodies, such as rituximab, and chemotherapy, such as cyclophosphamide, helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored for peripheral stem cell transplant. Giving chemotherapy, such as carmustine, etoposide, and cyclophosphamide, before transplant stops the growth of cancer cells by stopping them from dividing or killing them. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. More rituximab is given after transplant to kill any remaining cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with cyclophosphamide and G-CSF followed by combination chemotherapy works in treating patients undergoing an autologous stem cell transplant followed by rituximab and GM-CSF for refractory diffuse large B-cell lymphoma.

OBJECTIVES:

* Determine the disease-free and overall survival of patients with refractory diffuse large B-cell lymphoma treated with stem cell mobilization comprising rituximab, cyclophosphamide, and filgrastim (G-CSF) followed by high-dose chemotherapy comprising carmustine, etoposide, and cyclophosphamide and autologous peripheral blood stem cell transplantation, rituximab, and sargramostim (GM-CSF).
* Determine any potential infectious complications in patients treated with this regimen.
* Determine the effect of GM-CSF on antibody-dependent cellular cytotoxicity in patients treated with this regimen.

OUTLINE: Stem cell mobilization: Patients receive rituximab IV over 4-8 hours on days 1, 5, 8, and 13. Patients also receive cyclophosphamide IV over 1-2 hours on day 9 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 10 and continuing until an adequate number of peripheral blood stem cells (PBSC) are collected.

High-dose preparative regimen: Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2.

Autologous PBSC transplantation: Patients undergo autologous PBSC transplantation on day 0. Patients receive sargramostim (GM-CSF) SC once daily beginning on day 6 and continuing until blood counts recover.

Post-transplant regimen: Patients receive GM-CSF SC once daily on days 42-73, 177-208, 362-393, 543-574, and 727-758. Patients also receive rituximab IV over 4-8 hours on days 45, 52, 59, 66, 180,187, 194, 201, 365, 372, 379, 386, 546, 553, 560, 567, 730, 737, 744, and 751.

After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of diffuse large B-cell lymphoma, meeting 1 of the following criteria:

  * Failed to achieve at least partial remission
  * Failed to respond to prior primary therapy or salvage chemotherapy
  * Disease progression within 6 weeks after achieving remission
* CD20 expression at diagnosis or relapse
* No more than 4 prior regimens using chemotherapy, radiotherapy, or immunotherapy

  * The addition of radiotherapy or a monoclonal antibody to chemotherapy is considered 1 treatment regimen provided the addition was part of the initial treatment plan

    * The addition of these therapies due to lack of response or poor response is considered an additional treatment regimen whether given in the front line or salvage setting

PATIENT CHARACTERISTICS:

Performance status

* ECOG 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* Direct bilirubin ≤ 2 mg/dL
* AST or ALT \< 3 times upper limit of normal

Renal

* Creatinine ≤ 2.0 mg/dL

Cardiovascular

* Ejection fraction ≥ 40%

Pulmonary

* DLCO ≥ 60% of predicted

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* No active infection requiring oral or IV antibiotics
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* See Radiotherapy

Chemotherapy

* See Disease Characteristics

Radiotherapy

* See Disease Characteristics
* No prior radioimmunotherapy