ALLOGENEIC BONE-MARROW TRANSPLANTATION, ZIDOVUDINE, AND HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) INFECTION - STUDIES IN A PATIENT WITH NON-HODGKIN LYMPHOMA
ALLOGENEIC BONE-MARROW TRANSPLANTATION, ZIDOVUDINE, AND HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) INFECTION - STUDIES IN A PATIENT WITH NON-HODGKIN LYMPHOMA
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DOI：
10.7326/0003-4819-111-12-973
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发表时间：
1989-12-15
影响因子：
39.2
通讯作者：
SANTOS, GW
中科院分区：
文献类型：
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作者：
HOLLAND, HK;SARAL, R;SANTOS, GW
人类免疫缺陷病毒1型（HIV-1）感染的非霍奇金淋巴瘤患者被归类为获得性免疫缺陷综合征（AIDS）。异基因骨髓移植是治疗预后不良的淋巴瘤的一种成功方法。异基因骨髓移植和抗病毒药物齐多夫定的联合治疗具有保护新供体造血淋巴细胞和单核巨噬细胞免受HIV-1感染的潜在优势。一名感染HIV-1并患有淋巴瘤的41岁男子接受了大剂量环磷酰胺和全身照射，然后进行了异基因骨髓移植。在移植前，他接受高剂量齐多夫定2周（每4小时静脉注射5 mg/kg体重），移植后，他接受较低的维持剂量（每4小时静脉注射1.33 mg/kg体重）。未观察到齐多夫定引起的不良毒性。骨髓植入发生在第17天。染色体和限制性片段长度多态性分析表明完全嵌合体。移植后32天，外周血单个核细胞和骨髓样本培养和聚合酶链反应基因扩增均为HIV-1阴性。患者在移植后47天因肿瘤复发死亡。尸检组织分析显示，无论是通过培养（脑、骨髓、淋巴结和肿瘤标本）还是通过HIV-1 RNA和DNA序列的聚合酶链反应基因扩增（脑、骨髓、心脏、肾脏、肝脏、肺、直肠乙状结肠、脾脏和肿瘤标本），均无HIV-1证据。免疫学监测显示HIV-1抗体丢失。破伤风和白喉抗原均存在免疫转移。我们的病例表明，HIV-1感染的受体细胞可能已被根除继发于骨髓烧蚀性放化疗，齐多夫定可能能够防止建立HIV-1感染的供体造血淋巴细胞。
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.