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Syngeneic Bone Marrow Transplantation and Adoptive Transfer of Peripheral Blood Lymphocytes Combined with Zidovudine in Human Immunodeficiency Virus (HIV) Infection
- H. Clifford Lane, MD;
- Kathryn M. Zunich, MD;
- Wyndham Wilson, MD, PhD;
- Frank Cefali, BSN, RN;
- Margaret Easter, RN;
- Joseph A. Kovacs, MD;
- Henry Masur, MD;
- Susan F. Leitman, MD;
- H. G. Klein, MD;
- Ronald G. Steis, MD;
- Dan L. Longo, MD; and
- Anthony S. Fauci, MD
Abstract
Objective: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection.
Design: A partially randomized outpatient trial.
Setting: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility.
Patients: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic).
Interventions: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologie monitoring were done monthly.
Measurements and Main Results: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (± SE) CD4 cell percent (19.1% ± 3.1% to 28.1% ± 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation.
Conclusions: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIVspecific antigens.
Article and Author Information
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From the National Institutes of Health, Bethesda, Maryland. For current author addresses, see end of text.
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Requests for Reprints: H. Clifford Lane, MD, Building 10, Room 11B13, National Institutes of Health, Bethesda, MD 20892.
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Current Author Addresses: Drs. Lane and Zunich and Ms. Easter: National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 11B13, Bethesda, MD 20892.
Drs. Kovacs, Masur, and Mr. Cefali: Clinical Center, Building 10, Room 7D43, National Institutes of Health, Bethesda, MD 20892.
Drs. Leitman and Klein: Clinical Center, Building 10, Room 5D56, National Institutes of Health, Bethesda, MD 20892.
Dr. Wilson: National Cancer Institute, National Institutes of Health, Building 31, Room 3A49, Bethesda, MD 20892.
Dr. Steis: NCI-FCRDC, 501 W 7th Street, Suite 3, Frederick, MD 21701.
Dr. Longo: NCI-FCRDC, Building 567, Fort Detrick, Frederick, MD 21701.
Dr. Fauci: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 31, Room 7A03, Bethesda, MD 20892.
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