Ferreri Andrés J M, Ponzoni Maurilio, Guidoboni Massimo, Resti Antonio Giordano, Politi Letterio S, Cortelazzo Sergio, Demeter Judit, Zallio Francesco, Palmas Angelo, Muti Giuliana, Dognini Giuseppina P, Pasini Elisa, Lettini Antonia Anna, Sacchetti Federico, De Conciliis Carlo, Doglioni Claudio, Dolcetti Riccardo
Medical Oncology Unit, Department of Oncology, San Raffaele H Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
J Natl Cancer Inst. 2006 Oct 4;98(19):1375-82. doi: 10.1093/jnci/djj373.
An association between ocular adnexal MALT lymphoma (OAL) and Chlamydia psittaci (Cp) infection has been proposed, and recent reports suggest that doxycycline treatment causes tumor regression in patients with Cp-related OAL. The effectiveness of doxycycline treatment in Cp-negative OAL has not been tested.
In a prospective trial, 27 OAL patients (15 newly diagnosed and 12 having experienced relapse) were given a 3-week course of doxycycline therapy. Objective lymphoma response was assessed by computerized tomography scans or magnetic resonance imaging at 1, 3, and 6 months after the conclusion of therapy and every 6 months during follow-up. Cp infection in patients was determined by touchdown enzyme time-release polymerase chain reaction (TETR-PCR). Statistical tests were two-sided.
Eleven patients were Cp DNA-positive and 16 were Cp DNA negative. Doxycycline was well tolerated. At a median follow-up of 14 months, lymphoma regression was complete in six patients, and a partial response (> or = 50% reduction of all measurable lesions) was observed in seven patients (overall response rate [complete and partial responses] = 48%). Lymphoma regression was observed in both Cp DNA-positive patients (seven of 11 experienced regression) and Cp DNA-negative patients (six of 16 experienced regression) (64% versus 38%; P = .25, Fisher's exact test). The three patients with regional lymphadenopathies and three of the five patients with bilateral disease achieved objective response. In relapsed patients, response was observed both in previously irradiated and nonirradiated patients. The 2-year failure-free survival rate among the doxycycline-treated patients was 66% (95% confidence interval = 54 to 78), and 20 of the 27 patients were progression free.
Doxycycline is a fast, safe, and active therapy for Cp DNA-positive OAL that was effective even in patients with multiple failures involving previously irradiated areas or regional lymphadenopathies. The responses observed in PCR-negative OAL may suggest a need for development of more sensitive methods for Cp detection and investigation of the potential role of other doxycycline-sensitive bacteria.
有人提出眼附属器黏膜相关淋巴组织淋巴瘤（OAL）与鹦鹉热衣原体（Cp）感染之间存在关联，最近的报告表明，强力霉素治疗可使与Cp相关的OAL患者的肿瘤消退。强力霉素治疗Cp阴性OAL的有效性尚未得到检验。
在一项前瞻性试验中，27例OAL患者（15例新诊断患者和12例复发患者）接受了为期3周的强力霉素治疗。在治疗结束后1、3和6个月以及随访期间每6个月通过计算机断层扫描或磁共振成像评估客观淋巴瘤反应。通过触地酶延时聚合酶链反应（TETR-PCR）确定患者的Cp感染情况。统计检验采用双侧检验。
11例患者Cp DNA阳性，16例患者Cp DNA阴性。强力霉素耐受性良好。中位随访14个月时，6例患者淋巴瘤完全消退，7例患者观察到部分缓解（所有可测量病灶减少≥50%）（总缓解率[完全缓解和部分缓解] = 48%）。Cp DNA阳性患者（11例中有7例出现消退）和Cp DNA阴性患者（16例中有6例出现消退）均观察到淋巴瘤消退（64%对38%；P = 0.25，Fisher精确检验）。3例有区域淋巴结肿大的患者和5例双侧疾病患者中的3例实现了客观缓解。在复发患者中，既往接受过放疗和未接受过放疗的患者均观察到缓解。强力霉素治疗患者的2年无失败生存率为66%（95%置信区间 = 54%至78%），27例患者中有20例无进展。
强力霉素是一种治疗Cp DNA阳性OAL的快速、安全且有效的疗法，即使在涉及既往放疗区域或区域淋巴结肿大的多次治疗失败患者中也有效。在PCR阴性的OAL中观察到的缓解可能表明需要开发更敏感的Cp检测方法，并研究其他对强力霉素敏感细菌的潜在作用。
