Autologous Stem Cell Transplant in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

OBJECTIVES:

Primary

• Determine the 3-year progression-free survival of patients with progressive or recurrent Hodgkin's lymphoma treated with tandem autologous stem cell transplantation (2 courses of high-dose therapy with autologous stem cell rescue).
• Determine the response rate in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a pilot study. Patients are stratified according to risk (poor risk [primary progressive, recurrent, or resistant relapse] vs good risk [first recurrence]).

• Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy.
• Autologous hematopoietic stem cell collection: Patients undergo autologous hematopoietic stem cell collection. Patients with an inadequate number of collected stem cells are removed from the study.
• First preparative regimen: Patients receive high-dose melphalan IV continuously over 16 hours on day -1.
• First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. They also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover. At least 4-8 weeks later, patients proceed to second preparative regimen.
• Second preparative regimen: Patients receive high-dose carmustine IV over 1-2 hours on days -6, -5, and -4, etoposide IV over 4 hours on day -3, and cyclophosphamide IV over 2 hours on day -2. Beginning 36-48 hours later, patients proceed to the second autologous SCT (day 0).
• Second autologous SCT: Patients undergo second autologous SCT on day 0. Patients also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically* confirmed Hodgkin's lymphoma meeting ≥ 1 of the following criteria:

• Disease progression during initial first line chemotherapy
• Complete response lasting ≤ 90 days after induction
• Partial response lasting ≤ 90 days after induction
• First recurrence/progression with the duration of initial response ≤ 12 months after completion of chemotherapy NOTE: *There must be unequivocal radiological evidence of recurrent or progressive disease if biopsy was not obtained at time of disease recurrence/progression
• No clonal abnormalities in marrow collection
• Must have bilateral or unilateral bone marrow aspirates and biopsy within 42 days prior to stem cell collection
• Must have adequate sections of original diagnostic specimen available for review

• Needle aspirations or cytologies are not adequate
• No prior lymphoma, myelodysplastic syndromes, or leukemia (even if disease free ≥ 5 years)
• No CNS involvement

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 50-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal* (ULN) NOTE: *Unless due to Hodgkin's lymphoma

Renal

• Creatinine clearance ≥ 60 mL/min
• Creatinine ≤ 2.0 times ULN

Cardiovascular

• Ejection fraction ≥ 45% by 2-D echocardiogram
• No significant active cardiac disease

Pulmonary

• Adequate pulmonary function
• DLCO ≥ 45%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No known HIV or AIDS infection
• No active bacterial, fungal, or viral infection
• No medical condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics