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Allogeneic Bone Marrow Transplantation, Zidovudine, and Human Immunodeficiency Virus Type 1 (HIV-I) Infection: Studies in a Patient with Non-Hodgkin Lymphoma

H. Kent Holland, MD; Rein Saral, MD; John J. Rossi, PhD; Albert D. Donnenberg, PhD; William H. Burns, MD; William E. Beschorner, MD; Homayoon Farzadegan, PhD; Richard J. Jones, MD; Gerry V. Quinnan, MD; Georgia B. Vogelsang, MD; Huibert M. Vriesendorp, MD; John R. Wingard, MD; John A. Zaia, MD; and George W. Santos, MD
[+] Article, Author, and Disclosure Information

Grant Support: Supported in part by grants CA15396, CA06973, CA30206 from the National Cancer Institute and grant AI25959 from the National Institute of Allergy and Infectious Disease, National Institutes of Health; grant DAMD-17-88C-8019 from the United States Army; grants from the American Foundation for AIDS Research and the Harley Howell Foundation; and by contract 223-87-1107 from the Food and Drug Administration.

Requests for Reprints: Rein Saral, MD, Room 173, The Johns Hopkins Oncology Center, 600 North Wolfe Street, Baltimore, MD 21205.

Current Author Addresses: Drs. Holland, Saral, Donnenberg, Burns, Beschorner, Farzadegan, Jones, Vogelsang, Vriesendorp, Wingard, and Santos: The Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205.

Dr. Rossi: Department of Molecular Genetics, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010.

Dr. Quinnan: Center for Biologies Evaluation and Research, Food and Drug Administration, U.S. Public Health Service, Department of Health and Human Services, Bethesda, MD 20892.

Dr. Zaia: Division of Pediatrics, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010.

© 1989 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1989;111(12):973-981. doi:10.7326/0003-4819-111-12-973
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Human immunodeficiency virus type 1 (HIV-1)-infected patients with non-Hodgkin lymphoma are classified as having the acquired immunodeficiency syndrome (AIDS). Allogeneic bone marrow transplantation is a successful therapy for patients with lymphoma who have a poor prognosis. Combined therapy with allogeneic bone marrow transplantation and the antiviral drug zidovudine has the potential advantage of protecting the new donor hematopoietic-lymphoid and monocyte-macrophage cells from HIV-1 infection. A 41-year-old man infected with HIV-1 who had lymphoma was treated with high-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation. Before transplantation he received high-dose zidovudine for 2 weeks (5 mg/kg body weight intravenously every 4 hours) and after transplantation he received a lower maintenance dose (1.33 mg/kg body weight intravenously every 4 hours). No untoward toxicities attributable to zidovudine were observed. Bone marrow engraftment occurred on day 17. Chromosome and restriction fragment length polymorphism analyses demonstrated complete chimerism. Peripheral blood mononuclear cells and bone marrow samples were negative for HIV-1 by culture and polymerase chain reaction gene amplification 32 days after transplantation. The patient died 47 days after transplantation because of tumor relapse. Analysis of autopsy tissue showed no evidence of HIV-1 by either culture (brain, bone marrow, lymph node, and tumor specimens) or by polymerase chain reaction gene amplification for HIV-1 RNA and DNA sequences (brain, bone marrow, heart, kidney, liver, lung, rectosigmoid, spleen, and tumor specimens). Immunologic monitoring showed loss of HIV-1 antibody. Adoptive immunologic transfer was shown to be present to both tetanus and diphtheria antigens. Our case suggests that the HIV-1-infected recipient cells may have been eradicated secondary to the bone marrow ablative chemo-radiotherapy and that zidovudine may be able to prevent the establishment of HIV-1 infection in donor hematopoietic-lymphoid cells.





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