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人类免疫缺陷与霍奇金淋巴瘤。

Human immunodeficiency and Hodgkin lymphoma.

作者信息

Sissolak Gerhard, Sissolak Dagmar, Jacobs Peter

机构信息

Division of Clinical Haematology, Department of Internal Medicine, Faculty of Health Sciences, Stellenbosch University, Tygerberg Academic Hospital, South Africa.

出版信息

Transfus Apher Sci. 2010 Apr;42(2):131-9. doi: 10.1016/j.transci.2010.01.008.

Abstract

Presentation of Hodgkin lymphoma (HL) is distinctive in the infected individual being more advanced, accompanied by B symptoms and the presence of extranodal disease particularly lymphadenopathy of the head and neck. Bone marrow involvement may be found in over 50% of cases. Virtually all co express gamma-herpesvirus. Phenotypically there is prominence of the mixed-cellularity and lymphocyte depleted histopathologic subtypes that define an aggressive clinical course in comparison to other variants. Prior to the induction of cART, median survival was only 1-2 years. Notably the first chemotherapy trial using ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in 21 patients, without treating the viral infection, resulted in a 43% complete remission rate accompanied by severe haematological toxicities but did not extend median survival with this being 1.5 years matching the negative cases. Significant change accompanied concomitant anti-retroviral therapy that could be given safely even with dose intensive regimens exemplified by BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in 12 patients or the Stanford V regimen (doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, prednisone) coupled with involved-field radiation for bulky disease studied in 59 patients. BEACOPP extended overall survival (OS) to 83% at 2 years. A similar trend was seen when using the Stanford V regimen with an OS rate of 51% at 3 years, disease-free survival (DFS) of 68% and freedom from progression (FFP) in 60%. Additional benefits accrued from supportive care with stimulatory peptides such as G-CSF and when combined with bacterial prophylaxis results approached that found in the uninfected reference group. Current consensus holds this particular lymphoma as still among the non-AIDS defining cancers being lung, stomach, liver or anal despite these having recently gained more attention as several of these neoplasms may be occurring more commonly in the era of cART. While the relative risk of developing a non-AIDS-defining neoplasm in HIV-infected persons on the average is 2-3 times, the risk for developing HL in HIV-infected cases impressively ranges between 5 and 25 times when compared to the general population. Based on the precedent in which Kaposi sarcoma and the non-Hodgkin lymphomas distinctively alter the course of this retroviral infection in a way indistinguishable from concurrent Hodgkin lymphoma we propose that this entity be similarly regarded and the hypothesis tested in large randomised prospective study.

摘要

霍奇金淋巴瘤(HL)在感染个体中的表现较为独特,病情往往更严重,伴有B症状且存在结外病变,尤其是头颈部淋巴结病。超过50%的病例可能会出现骨髓受累。几乎所有病例都共同表达γ-疱疹病毒。从表型上看,混合细胞型和淋巴细胞消减型组织病理学亚型较为突出,与其他亚型相比,这两种亚型具有侵袭性的临床病程。在开始抗逆转录病毒治疗(cART)之前,中位生存期仅为1至2年。值得注意的是,在21例患者中进行的首次使用ABVD(多柔比星、博来霉素、长春碱和达卡巴嗪)的化疗试验,未治疗病毒感染,完全缓解率为43%,伴有严重的血液学毒性,但并未延长中位生存期,中位生存期为1.5年,与未治疗组相当。随着抗逆转录病毒治疗的同时使用,情况发生了显著变化,即使是采用剂量密集型方案如BEACOPP(博来霉素、依托泊苷、多柔比星、环磷酰胺、长春新碱、丙卡巴肼和泼尼松)治疗12例患者,或采用斯坦福V方案(多柔比星、长春碱、氮芥、依托泊苷、长春新碱、博来霉素、泼尼松)联合受累野放疗治疗59例大块病灶患者,都能安全给药。BEACOPP将2年总生存率(OS)提高到了83%。使用斯坦福V方案时也观察到了类似趋势,3年OS率为51%,无病生存率(DFS)为68%,无进展生存率(FFP)为60%。使用刺激肽如粒细胞集落刺激因子(G-CSF)进行支持治疗以及联合细菌预防可带来额外益处,结果接近未感染参照组。目前的共识认为,尽管在cART时代,这些非艾滋病定义的癌症(如肺癌、胃癌、肝癌或肛门癌)最近受到了更多关注,但这种特殊的淋巴瘤仍属于非艾滋病定义的癌症。虽然HIV感染者发生非艾滋病定义肿瘤的平均相对风险是2至3倍,但与普通人群相比,HIV感染病例发生HL的风险显著在5至25倍之间。基于卡波西肉瘤和非霍奇金淋巴瘤以与并发霍奇金淋巴瘤难以区分的方式显著改变这种逆转录病毒感染病程的先例,我们建议对该实体进行类似的看待,并在大型随机前瞻性研究中对这一假设进行检验。

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