RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.

OBJECTIVES:

• Determine the long term disease-free survival of patients with mantle cell lymphoma treated with etoposide, carmustine, melphalan, and cytarabine followed by allogeneic peripheral blood stem cell transplantation.
• Determine the incidence of molecular remissions in these patients treated with this regimen.
• Correlate the persistence of minimal residual disease with clinical outcome in these patients treated with this regimen.
• Determine the effect of donor lymphocytes in patients with progressive disease after treatment with this regimen.

OUTLINE: This is a multicenter study.

Patients receive carmustine IV over 2 hours on day -6; etoposide IV over 3 hours and cytarabine IV over 1 hour every 12 hours on days -5 to -2 for a total of 8 doses; and melphalan IV over 20-30 minutes on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus IV continuously over 24 hours beginning on day -2 and then orally twice daily until day 120 and methotrexate IV over 30 minutes on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim (GM-CSF) IV or subcutaneously daily beginning on day 7 and continuing until blood counts recover.

Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists.

Patients are followed at 6 and 12 months posttransplantation and then annually for 4 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3.5 years.

• Graft Versus Host Disease
• Lymphoma

• Biological: sargramostim
• Biological: therapeutic allogeneic lymphocytes
• Drug: carmustine
• Drug: cytarabine
• Drug: etoposide
• Drug: melphalan
• Drug: methotrexate
• Drug: tacrolimus
• Procedure: peripheral blood stem cell transplantation

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma of any stage with at least 1 of the following:

  • Immunophenotype with expression of CD5 and CD19 and absence of CD23
  • Cytogenetic analysis with presence of t(11;14)
  • Overexpression of cyclin D1
  • Rearrangement of BCL1 gene

• Bone marrow biopsy required

  • No needle or core biopsy as sole means of diagnosis

• First remission allowed if at least 1 of the following poor prognostic characteristics present:

  • International Prognostic Index (IPI) score higher than 1 defined by the following risk factors:

    • Performance status higher than 1
    • Elevated LDH
    • Presence of more than 1 extranodal site
    • Stage III or IV disease
  • Blastic variant of mantle cell lymphoma*
  • Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14)*
  • Proliferative index more than 10%*
  • Presence of p53 mutations NOTE: *Regardless of IPI score

• Failure of initial therapy with anthracycline-containing regimen allowed

  • Failure to achieve clinical complete remission after initial therapy OR
  • Recurrent disease after initial therapy

• HLA matched (6/6) sibling donor by serologic typing (A, B, or DR)

  • Any age
  • No syngeneic (identical twin) donor
• No active CNS lymphoma

PATIENT CHARACTERISTICS:

Age:

• Under 60

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2 mg/dL
• AST and ALT no greater than 3 times upper limit of normal

Renal:

• Creatinine less than 2 mg/dL

Pulmonary:

• DLCO at least 40%
• No symptomatic pulmonary disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow transplantation

Chemotherapy:

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy

Radiotherapy:

• No concurrent radiotherapy to bulky sites

Surgery:

• See Disease Characteristics