Allogeneic bone marrow transplantation, zidovudine, and human immunodeficiency virus type 1 (HIV-1) infection. Studies in a patient with non-Hodgkin lymphoma.
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.
Holland
H K
HK
Johns Hopkins School of Medicine, Baltimore, Maryland.
Saral
R
R
Rossi
J J
JJ
Donnenberg
A D
AD
Burns
W H
WH
Beschorner
W E
WE
Farzadegan
H
H
Jones
R J
RJ
Quinnan
G V
GV
Vogelsang
G B
GB
D000328:Adult; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D015683:Gene Products, gag / Q000032:analysis; D015488:HIV Antigens / Q000032:analysis; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000628:therapy*; D008297:Male; D016133:Polymerase Chain Reaction; D014758:Viral Core Proteins / Q000032:analysis; D014916:Whole-Body Irradiation; D015215:Zidovudine / Q000493:pharmacokinetics / Q000627:therapeutic use*
D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D014758:Viral Core Proteins; D015215:Zidovudine; D003520:Cyclophosphamide