Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

This clinical trial studies genetically modified peripheral blood stem cell transplant in treating patients with HIV-associated non-Hodgkin or Hodgkin lymphoma. Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. Laboratory-treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of infusing gene-modified, human immunodeficiency virus (HIV)-protected hematopoietic stem cells (HSC) after high-dose chemotherapy for treatment of acquired immunodeficiency syndrome (AIDS)-related lymphoma.

II. To determine the dose of carmustine (BCNU) in combination with O\^6-benzylguanine (O6BG) that results in selection in vivo of gene-modified HIV-resistant cells.

III. To estimate the effect of HIV infection on the presence of HIV-resistant blood cells as measured by genetic marking for vector sequences before and after antiviral treatment interruption.

SECONDARY OBJECTIVES:

I. Evaluate the molecular and clonal composition of gene-modified cells after hematopoietic cell transplant (HCT).

II. Evaluate the molecular and clonal composition of gene-modified cells after O6BG/BCNU.

III. Determine the correlation of the level of O6-methylguanine- methyltransferase (MGMT) (P140K) marking with toxicity and response.

IV. Characterize the toxicity associated with in vivo selection. V. Determine the efficacy of the procedure for treatment of lymphoma: defined as time to disease progression, progression-free survival, treatment-related mortality, time to neutrophil and platelet recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. Effect of procedure on the latent HIV reservoir. II. Effect of procedure on HIV-specific immune reconstitution.

OUTLINE:

CONDITIONING: Patients receive carmustine intravenously (IV) over 3 hours on day -7, cytarabine IV over 2 hours twice daily (BID) and etoposide IV over 2 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: Patients receive an autologous PBSC infusion and/or infusion of autologous transduced hematopoietic cells on day 0.

Beginning 28-120 days later, patients eligible for in vivo selection after detection of gene-marked cells receive O6-benzylguanine IV over 1 hour and carmustine IV over 3 hours on days 14, 28, and then monthly until completion of therapy. Patients achieving \> 10% gene marking and CD4 count of \>= 500 cells/uL receive up to 2 courses of structured treatment interruption without undergoing in vivo selection.

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

Eligibility Criteria:
Inclusion Criteria:

* HIV seropositive
* Antiretroviral treatment for at least one month, defined as a multi-drug regimen (excluding azacitidine \[AZT\])
* HIV plasma viral load has decreased by 1.5 logs or viral load \< 5000 copies/ml
* Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:

  * Hodgkin's lymphoma beyond first remission; first partial remission; induction failure with subsequent response to salvage therapy
  * Non-Hodgkin's Lymphoma beyond first remission: first partial remission; induction failure with subsequent response to salvage therapy
  * Chemotherapy responsive disease
* Karnofsky performance score \>= 70%
* Subjects must agree to use effective contraception from enrollment through completion of the study
* Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of treatment
* Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the cluster of differentiation (CD)4 counts are =\< 200
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Serum creatinine \> 2 times upper limit of normal
* Serum bilirubin greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
* Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung of carbon monoxide (DLCO) parameters \< 60% predicted (corrected for hemoglobin)
* Left ventricular ejection fraction (LVEF) \< 50% or coronary artery disease requiring treatment
* Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
* Patients who are hepatitis C virus (HCV) antibody positive or hepatitis B virus (HBV) surface antigen positive must be free of clinical evidence of cirrhosis that would otherwise make them ineligible for HCT, as determined by the Principal Investigator (P.I.) in consultation with the Gastrointestinal Service; patients with HBV and ongoing evidence of viral replication may require therapy prior to receiving high-dose chemotherapy
* Positive serology for Toxoplasma gondii AND requiring treatment or with evidence of active infection
* Malignancy other than lymphoma, unless 1) in complete remission and more than 5 years from last treatment), or 2) cervical/anal squamous cell carcinoma in situ or 3) superficial basal cell and squamous cell cancers of the skin
* History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent (Note: Consent may not be obtained by means of a legal guardian)
* A medical history of noncompliance with highly active anti-retroviral therapy (HAART) or medical therapy