Implication of HTLV-I infection, strongyloidiasis, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphomas in an endemic area (Martinique, French West Indies).

P Agapé, M C Copin, M Cavrois, G Panelatti, Y Plumelle, M Ossondo-Landeau, D Quist, N Grossat, B Gosselin, P Fenaux, E Wattel
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引用次数: 25

Abstract

A clinicopathologic study was conducted to assess the implication of HTLV-I infection, Strongyloides stercoralis (Ss) infection, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphoma (NHL) in Martinique, French West Indies. Two groups of patients, with 22 and 41 participants with B-cell and T-cell lymphoma, respectively, were analyzed. HTLV-I antibodies were detected in 24 (59%) patients with T-cell lymphoma of whom 19 (46%) fulfilled diagnostic criteria of adult T-cell leukemia/lymphoma (ATLL). By comparison with other T-cell lymphomas, patients with ATLL were significantly younger (52 versus 63 years; p = .03), had a significantly higher incidence of hypercalcemia (60% versus 0%; p = .0001), a trend for higher incidence of digestive tract localization (21% versus 4%; p = .1) and significantly shorter median survival (6 versus 17 months; p = .03). Similar results were observed when all 24 HTLV-I-infected patients with T-cell lymphoma were compared with the 17 seronegative patients. Strongyloidiasis was diagnosed in 11 of 34 patients tested for Ss infection. All 4 Ss-infected (Ss-positive) ATLL patients treated with combination chemotherapy achieved complete remission (CR) versus only 2 of 7 Ss-negative ATLL patients (p = .04). In addition, survival of Ss-positive patients with ATLL was better than that of the uninfected patients: 27 versus 5 months, p = .04, respectively). P53 expression was assessed by immunohistochemistry on lymph node biopsies from 37 patients including 18 B-cell lymphomas, 14 ATLL, and 5 other T-cell lymphomas. P53 overexpression (P53-positive) was observed in 6 samples that corresponded in all 6 patients with ATLL. All P53-positive ATLL patients had stage IV disease with elevated lactate dehydrogenase (LDH) levels. By comparison with other ATLL patients studied for p53 expression, P53-positive ATLL were characterized by a lower response rate to combination chemotherapy (CR: 0 of 6 versus 4 of 6; p = .04) and a shorter survival (2 versus 9 months, p = .04). Our results suggest that ATLL represents almost 50% of T-cell lymphomas in Martinique; Ss infection during ATLL seems to be linked with a high response rate to chemotherapy and prolonged survival; and P53 overexpression is observed in almost 50% of aggressive ATLL from Martinique and, even in advanced clinical subtypes, is associated with resistance to chemotherapy and short-term survival.

htlv - 1感染、类圆线虫病和P53过表达在流行地区(马提尼克岛、法属西印度群岛)非霍奇金淋巴瘤的发展、治疗反应和演变中的意义
一项临床病理研究旨在评估htlv - 1感染、肠类圆杆菌(Ss)感染和P53过表达在法属西印度群岛马提尼克岛非霍奇金淋巴瘤(NHL)的发展、治疗反应和演变中的意义。分析了两组患者,分别有22名和41名b细胞和t细胞淋巴瘤患者。24例(59%)t细胞淋巴瘤患者检测到HTLV-I抗体,其中19例(46%)符合成人t细胞白血病/淋巴瘤(ATLL)的诊断标准。与其他t细胞淋巴瘤相比,ATLL患者明显更年轻(52岁vs 63岁;P = .03),高钙血症发生率显著高于对照组(60% vs 0%;P = 0.0001),消化道定位的发生率有较高的趋势(21%对4%;P = 0.1),中位生存期显著缩短(6个月vs 17个月;P = .03)。将所有24例htlv -i感染的t细胞淋巴瘤患者与17例血清阴性患者进行比较,观察到类似的结果。34例Ss感染患者中有11例被诊断为类圆线虫病。所有4例ss感染(ss阳性)ATLL患者接受联合化疗后均达到完全缓解(CR),而7例ss阴性ATLL患者中只有2例(p = 0.04)。此外,ss阳性ATLL患者的生存期优于未感染患者(27个月vs 5个月,p = 0.04)。对37例患者的淋巴结活检,包括18例b细胞淋巴瘤,14例ATLL和5例其他t细胞淋巴瘤,采用免疫组织化学方法评估P53的表达。6个样本中P53过表达(P53阳性),与所有6例ATLL患者相对应。所有p53阳性的ATLL患者均为IV期疾病,乳酸脱氢酶(LDH)水平升高。与其他研究p53表达的ATLL患者相比,p53阳性的ATLL患者对联合化疗的反应率较低(CR: 0 / 6比4 / 6;P = .04)和较短的生存期(2个月对9个月,P = .04)。我们的研究结果表明,ATLL几乎占马提尼克岛t细胞淋巴瘤的50%;ATLL期间的Ss感染似乎与化疗的高反应率和延长的生存期有关;在马提尼克岛近50%的侵袭性ATLL患者中观察到P53过表达,甚至在晚期临床亚型中,也与化疗耐药和短期生存有关。
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