Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases
Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases
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DOI：
10.1200/jco.1996.14.6.1943
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发表时间：
1996-06-01
影响因子：
45.3
通讯作者：
Murren, J
中科院分区：
文献类型：
--
作者：
Salloum, E;Cooper, DL;Murren, J
目的：确定在甲氨蝶呤（MTX）治疗风湿性疾病（RD）的背景下发生的淋巴组织增生性疾病（LPD）的临床病理学特征，并确定肿瘤细胞中EB病毒（EBV）的存在与LPD对MTX停药的反应之间的关系。除了9例新病例外，我们分析了文献中先前报道的28例接受MTX治疗RD的LPD患者，除MTX外，19例患者的免疫抑制治疗包括皮质类固醇，16例患者中发现有结外病变，但无CNS受累。病理结果包括5例何杰金氏病和7例低度恶性淋巴瘤，其余患者为中度或侵袭性淋巴瘤。结果：37例患者中，16例在MTX停药后未加用抗肿瘤药物治疗时，EBV-RNA转录本原位杂交（ISHS）检测阳性。6例达到自发完全缓解（CR），3例有部分缓解（PR），1例有最小缓解，6例对MTX停药无反应。在10例有反应的患者中，通过ISHS（n = 6）或聚合酶链反应（PCR）（n = 2）检测到EBV; 1例患者尽管通过PCR检测不到EBV，但仍达到CR，1例达到CR，但未进行病毒检测。结论：MTX治疗后出现LPD的患者，在初始治疗时应考虑MTX停药并观察一段时间，但不限于用ISHS或PCR检测到EBV的患者，其疗效是一致的。需要进一步的研究来证实这些发现，并评估EBV在接受MTX治疗的患者发生LPD中的作用。(C)1996年，美国临床肿瘤学会。
Purpose: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal.Patients and Methods: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD, In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one, Extranodal disease was identified in 16 patients, bur none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas, The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%).Results: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor ther-apy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal, Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal.Conclusion: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy, Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies ore required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX. (C) 1996 by American Society of Clinical Oncology.