• Safety [ Designated as safety issue: Yes ]
• Feasibility [ Designated as safety issue: No ]

• Safety
• Feasibility

RATIONALE: Placing a gene from HIV into a patient's stem cells may make the body build an immune response to kill cancer cells in patients with AIDS-related lymphoma.

PURPOSE: This clinical trial is studying the side effects and best dose of gene therapy in treating patients undergoing a stem cell transplant for intermediate-grade or high-grade AIDS-related lymphoma.

OBJECTIVES:

• To determine the safety and feasibility of using lentivirus-transduced hematopoietic progenitor cells (HPCs) in the setting of autologous hematopoietic stem cell transplantation in patients with AIDS-related lymphoma.
• To determine the quantity and duration of vector-marked peripheral blood cells and to characterize the duration and level of gene marking and expression of the anti-HIV RNAs in these transduced cells and the integration sites of vector sequences in circulating cells, if there is a clinical syndrome suggestive of a clonal expansion of hematopoietic cells.
• To determine whether the design of the vector prevents vector mobilization and rescue by wild-type HIV-1.

OUTLINE: Patients undergo hematopoietic progenitor cell (HPC) mobilization with a combination of chemotherapy (using their prior antilymphoma regimen or cyclophosphamide) and filgrastim (G-CSF). Approximately 24 hours after completion of chemotherapy, patients receive G-CSF subcutaneously daily until the last apheresis is completed. A portion of the apheresis products are transduced with rHIV7-shI-TAR-CCR5RZ.

Patients receive high-dose conditioning regimen comprising carmustine IV over 4 hours on days -7 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients receive rHIV7-shI-TAR-CCR5RZ-transduced autologous HPCs IV over approximately 30 minutes on day 0 and standard non-transduced autologous HPCs IV over 30 minutes on day 1.

NOTE: Patients continue their anti-HIV regimen during antilymphoma chemotherapy, as prescribed by the physician managing their HIV infection; patients stop the anti-HIV regimen at the time of initiating HPC mobilization with G-CSF and resume it after the last apheresis is completed; patients also stop the anti-HIV regimen on day -7 (initiation of high-dose conditioning) and resume it on day 3 (post-transplantation).

After completion of study therapy, patients are followed periodically for up to 15 years.

• Biological: filgrastim
• Biological: gene therapy
• Drug: carmustine
• Drug: cyclophosphamide
• Drug: etoposide
• Procedure: autologous hematopoietic stem cell transplantation
• Procedure: in vitro-treated peripheral blood stem cell transplantation

DISEASE CHARACTERISTICS:

• HIV seropositive at or before the time of lymphoma diagnosis

  • No detectible HIV-1 that has CXCR4-tropism

  • Must be on a multi-drug anti-HIV regimen (excluding zidovudine [AZT]) and have an HIV viral load < 50,000 copies/mL by RT-PCR at the time of study enrollment

    • Must agree to have anti-HIV regimen (HAART) temporarily stopped from the time filgrastim (G-CSF) is initiated for hematopoietic progenitor cell (HPC) mobilization until the mobilization is complete (approximately 7 days)
  • Must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the CD4 count is ≤ 200/mm³

• Meets 1 of the following criteria:

  • Biopsy proven intermediate- or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria:

    • In first complete remission with high-risk features as specified by the International Prognostic Index
    • In partial remission
    • Relapsed after initial complete remission
    • Failed induction therapy but responds to salvage therapy (i.e., chemosensitive disease)

  • Biopsy-proven Hodgkin lymphoma, meeting 1 of the following criteria:

    • In first or greater relapse after initial complete remission
    • In partial remission
    • Failed induction therapy but responds to salvage therapy (i.e., chemosensitive disease)
• Patients with prior marrow involvement must demonstrate ≤ 10% involvement prior to stem cell collection
• No abnormal cytogenetics not related to the lymphoma

• No active CNS lymphoma

  • Patients with a history of positive cerebrospinal fluid cytology that has become negative with intrathecal chemotherapy are eligible
• No history of HIV-associated encephalopathy
• No other AIDS-related syndromes that are perceived to cause excessive risk for morbidity post-transplantation, as determined by the principal investigator

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)
• Serum bilirubin ≤ 2.5 times ULN
• Patients who are hepatitis C virus antibody positive or hepatitis B virus surface antigen positive must be free of clinical evidence of cirrhosis as determined by the principal investigator in consultation with the Gastrointestinal Service
• Amylase and lipase normal
• Serum creatinine ≤ 2 times ULN
• Creatinine clearance ≥ 60 mL/min
• PT/PTT ≤ 2 times normal
• Other laboratory value for CBC and chemistry panel ≤ 2 times ULN
• FEV_1 or DLCO ≥ 50% predicted
• LVEF ≥ 50% by 2-D ECHO or MUGA scan
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after transplantation
• No symptomatic bacterial or fungal infection
• No AIDS-related opportunistic infections within the past year for which treatment has been unsuccessful, as determined by the principal investigator

• No active CMV retinitis or other active CMV-related organ dysfunction

  • Patients with a history of treated CMV infection are eligible
• No relapse of Pneumocystis carinii pneumonia within the past year
• No intractable, severe diarrhea, defined as > 1,500 cc diarrheal fluid per day, or diarrhea causing persistent severe electrolyte abnormalities or hypoalbuminemia
• No history of myocardial infarction or congestive heart failure
• No cardiomyopathy or dysrhythmia
• No dementia of any kind
• No seizures within the past 12 months
• No history of grade III hemorrhagic cystitis due to prior cyclophosphamide chemotherapy
• No other prior malignancy, except squamous cell carcinoma of the cervix or anus, superficial basal cell or squamous cell skin cancer, or other malignancy curatively treated ≥ 5 years ago
• No psychosocial condition that would hinder study compliance and follow-up

• No perceived inability to directly provide informed consent

  • Consent may not be obtained by means of a legal guardian
• No medical or physical contraindication or other inability to undergo HPC collection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics