Comoli P, Basso S, Zecca M, Pagliara D, Baldanti F, Bernardo M E, Barberi W, Moretta A, Labirio M, Paulli M, Furione M, Maccario R, Locatelli F
Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy.
Am J Transplant. 2007 Jun;7(6):1648-55. doi: 10.1111/j.1600-6143.2007.01823.x.
The treatment of Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell transplantation (HSCT) is still unsatisfactory. We conducted a prospective trial to evaluate the impact of routine EBV surveillance and preemptive treatment with the anti-CD20 monoclonal antibody rituximab on the development of PTLD in pediatric recipients of extensively T-cell depleted HSCT from an HLA-haploidentical relative. Twenty-seven patients were included in the surveillance program, 12 developed EBV DNA positivity, with 8 of 12 presenting with sustained viral DNA levels requiring treatment with rituximab. Treatment was well tolerated, and induced clearance of EBV DNA in all patients. However, 4/8 patients showed a new increase in EBV load, coincident with the emergence of CD20(-)/CD19(+) B cells in peripheral blood, accompanied by overt PTLD in 3 patients. The latter cleared PTLD after receiving donor EBV-specific cytotoxic T-lymphocytes (CTLs), and persist in remission at a median 30-month follow-up. EBV-specific T-cell frequency, undetectable at time of EBV DNA positivity, was restored by T-cell therapy to levels comparable with controls. We conclude that preemptive therapy with rituximab is safe, but only partly effective in haplo-HSCT recipients. Patients who progress to PTLD under rituximab treatment can be rescued permanently by infusion of EBV-specific CTLs.
造血干细胞移植（HSCT）后，爱泼斯坦-巴尔病毒（EBV）相关的移植后淋巴细胞增殖性疾病（PTLD）的治疗仍不尽人意。我们进行了一项前瞻性试验，以评估常规EBV监测和使用抗CD20单克隆抗体利妥昔单抗进行抢先治疗对来自HLA单倍体相合亲属的广泛T细胞去除的HSCT儿科受者中PTLD发生的影响。27名患者被纳入监测计划，12名出现EBV DNA阳性，其中12名中有8名出现持续病毒DNA水平，需要用利妥昔单抗治疗。治疗耐受性良好，并使所有患者的EBV DNA清除。然而，4/8患者的EBV载量出现新的增加，与外周血中CD20（-）/CD19（+）B细胞的出现同时发生，3名患者伴有明显的PTLD。后者在接受供体EBV特异性细胞毒性T淋巴细胞（CTL）后清除了PTLD，并在中位30个月的随访中持续缓解。在EBV DNA阳性时无法检测到的EBV特异性T细胞频率通过T细胞疗法恢复到与对照组相当的水平。我们得出结论，利妥昔单抗抢先治疗是安全的，但在单倍体HSCT受者中仅部分有效。在利妥昔单抗治疗下进展为PTLD的患者可以通过输注EBV特异性CTL得到永久挽救。
