Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

This clinical trial studies the side effects and best dose of giving fludarabine and total-body irradiation (TBI) together followed by a donor stem cell transplant and cyclosporine and mycophenolate mofetil in treating human immunodeficiency virus (HIV)-positive patients with or without cancer. Giving low doses of chemotherapy, such as fludarabine, and TBI before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after the transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. To determine the safety of treating high-risk HIV1-infected patients with 200 centigray (cGy) TBI plus post-transplant MMF/CSP.

II. To determine whether 200 cGy TBI plus post-transplant MMF/CSP results in stable mixed donor lymphocyte chimerism (5-95% donor cluster of differentiation \[CD\]3) in high-risk human immunodeficiency virus (HIV)-1 infected patients.

SECONDARY OBJECTIVES:

I. To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in HIV1-infected patients.

II. To determine the effect of a non-lethal conditioning regimen on viral load.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0.

TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine IV or orally (PO) 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of graft-vs-host disease (GVHD). Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.

After completion of study treatment, patients are followed up for at least 1 year.

Eligibility Criteria:
Inclusion Criteria:

* Patients with hematologic malignancy, lymphoma or other HIV-associated malignancy are eligible provided these criteria are met:

  * The malignancy is in complete remission or very good partial remission, defined as a significant reduction of disease with therapy and no evidence for continued tumor growth in the case of lymphoma or solid tumors
  * Highly active antiretroviral therapy (HAART) is initiated within one month of hematopoietic cell transplant
  * Viral load has decreased by \>= 1.5 logs or viral load \< 5000 copies/ml plasma on HAART therapy
  * CD4 count is allowed to be \> 100 cells/ul
* HIV infected patients without malignancy who have failed HAART are eligible provided that these criteria are met:

  * They have been treated with more than one regimen of HAART for a total of at least 6 months duration
  * The viral load is \< 50 copies/ml plasma
  * The CD4 count \< 100 cells/ul
* DONOR: Human leukocyte antigen (HLA) genotypically/phenotypically identical donor; if more than one HLA-identical sibling is available, priority will be given to donors matched for cytomegalovirus (CMV) status, ABO titer, and sex

  * Peripheral blood stem cells will be collected from donors greater than 12 years of age
  * Bone marrow will be collected from donors less than 12 years of age
* DONOR: HLA phenotypically identical unrelated donor; match grades allowed:

  * Match grade 1: Matched at allele level for HLA-A, B, C, DRB1, and DQB1
  * Match grade 2.1: Single allele disparity for HLA-A, B, C, DRB1, and DQB1

Exclusion Criteria:

* Positive serology for toxoplasma gondii on treatment or with evidence of active infection
* Patients with other disease or organ dysfunction that would limit survival to less than 30 days
* Patients with medical history of noncompliance with HAART or medical therapy
* DONOR: Donors for whom medical or psychologic reasons would make donor procedure intolerable
* DONOR: Marrow donors who have increased anesthetic risk
* DONOR: Donors who are HIV positive
* DONOR: Age \> 75 years