Darenkov I A, Marcarelli M A, Basadonna G P, Friedman A L, Lorber K M, Howe J G, Crouch J, Bia M J, Kliger A S, Lorber M I
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.
Transplantation. 1997 Sep 27;64(6):848-52. doi: 10.1097/00007890-199709270-00010.
Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD.
To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen.
Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy.
Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.
随着更有效、更强效免疫抑制药物的出现,移植后淋巴细胞增生性疾病(PTLD)的发生率日益增加。先前的研究表明,在179例连续移植受者中,有7例(3.9%)通过检测外周血B淋巴细胞增生的监测策略在PTLD早期诊断中取得了成效。这7例患者在发生PTLD之前均接受了至少一个疗程的抗胸腺细胞球蛋白、明尼苏达抗淋巴细胞球蛋白或OKT3治疗。
为确定抗病毒预防措施是否可降低PTLD的发生率,随后的198例连续受者在接受抗淋巴细胞抗体治疗期间,分别接受了更昔洛韦或阿昔洛韦治疗。当供者或受者巨细胞病毒血清学呈阳性时,给予更昔洛韦;当两者均为巨细胞病毒血清学阴性时,使用阿昔洛韦。采用免疫荧光和流式细胞术获取移植后基线和方案规定的细胞表面特征,以检测T细胞、淋巴细胞活化标志物和CD19 B细胞抗原。
两组的人口统计学因素相似,包括50岁以上受者、非白种人、既往移植史和糖尿病的发生率。此外,接受抗淋巴细胞制剂的患者数量也相似。然而,后一组接受抢先抗病毒治疗的患者中只有1例(0.5%)发生了PTLD。虽然在之前的7例患者中,CD19 + B细胞升高均先于临床PTLD出现,但后一组唯一的患者未出现外周B细胞增生的证据,这表明抗病毒治疗可能有一定作用。
预防性抗病毒治疗可能会降低外周监测B淋巴细胞增生的敏感性,但PTLD发生率的显著降低有力地支持了在有风险的移植受者中使用该治疗方法。