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接受克拉屈滨(2-氯脱氧腺苷)治疗的患者发生输血相关移植物抗宿主病:通过聚合酶链反应分析在各种组织提取物中证实存在外源性DNA

Transfusion-associated graft-versus-host disease in a patient treated with Cladribine (2-chlorodeoxyadenosine): demonstration of exogenous DNA in various tissue extracts by PCR analysis.

作者信息

Zulian G B, Roux E, Tiercy J M, Extermann M, Diebold-Berger S, Reymond J M, Helg C, Zubler R, Betticher D C, Alberto P

机构信息

Division of Onco-haematology, Geneva University Hospital, Switzerland.

出版信息

Br J Haematol. 1995 Jan;89(1):83-9. doi: 10.1111/j.1365-2141.1995.tb08906.x.

Abstract

Transfusion-associated graft-versus-host disease can occur in both immunocompetent and immunocompromised hosts. Cladribine is a synthetic analogue of adenine used in the treatment of lymphoid malignancies, commonly associated with a decrease in T lymphocytes. Cladribine was given for a low-grade non-Hodgkin's lymphoma with thrombocytopenia as the main side-effect. Six units of pooled non-irradiated platelets were transfused from six unrelated donors; 10 d later a clinical picture typical of graft-versus-host disease resulted. Polymerase chain reaction of the highly polymorphic DNA minisatellites and HLA-DR oligotyping were used to demonstrate the exogenous DNA. In the patient's blood and tissues, only the pattern of donor 5 was found. The patient (DRB10301/1101; DRB30101/02) and this donor (DRB10301/1104; DRB302) by chance shared a partial common haplotype. This complication highlights the sensitivity of DNA minisatellite analysis. It further raises the question of transfusion and of prophylactic irradiation of all blood products in immunosuppressed patients and those treated with cladribine. This case represents a previously unreported situation where an immunosuppressed patient was able to eliminate cells from five totally HLA-DR dissimilar donors but not from one heterozygous donor with strong HLA-DR similarity.

摘要

输血相关移植物抗宿主病可发生在免疫功能正常和免疫功能低下的宿主中。克拉屈滨是一种用于治疗淋巴系统恶性肿瘤的腺嘌呤合成类似物,通常会导致T淋巴细胞减少。克拉屈滨用于治疗以血小板减少为主要副作用的低度非霍奇金淋巴瘤。从六名无关供者输注了六个单位的混合未辐照血小板;10天后出现了典型的移植物抗宿主病临床表现。利用高度多态性的DNA小卫星聚合酶链反应和HLA-DR寡核苷酸分型来证实外源性DNA。在患者的血液和组织中,仅发现了供者5的图谱。患者(DRB10301/1101;DRB30101/02)与该供者(DRB10301/1104;DRB302)偶然共享了部分共同单倍型。这一并发症凸显了DNA小卫星分析的敏感性。它进一步引发了关于输血以及对免疫抑制患者和接受克拉屈滨治疗的患者的所有血液制品进行预防性辐照的问题。该病例代表了一种此前未报道的情况,即一名免疫抑制患者能够清除来自五名HLA-DR完全不同的供者的细胞,但无法清除来自一名具有高度HLA-DR相似性的杂合供者的细胞。

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