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利妥昔单抗联合氟达拉滨和米托蒽醌(R-FM)治疗胃黏膜相关淋巴组织边缘区淋巴瘤的长期疗效及毒性:单中心经验及文献综述

Long-term efficacy and toxicity of rituximab plus fludarabine and mitoxantrone (R-FM) for gastric marginal zone lymphoma: a single-center experience and literature review.

作者信息

Cencini Emanuele, Fabbri Alberto, Lauria Francesco, Bocchia Monica

机构信息

Haematology Unit, Azienda Ospedaliera Universitaria Senese, Viale Bracci, 16, 53100, Siena, Italy.

University of Siena, Siena, Italy.

出版信息

Ann Hematol. 2018 May;97(5):821-829. doi: 10.1007/s00277-018-3243-7. Epub 2018 Jan 16.

Abstract

There is no consensus about the best treatment option for patients with HP-negative gastric MALT lymphomas or persistent disease after HP eradication.We have investigated fludarabine and mitoxantrone with rituximab (R-FM) as first-line treatment. A cohort of 13 patients was analyzed. Induction treatment consisted of fludarabine (25 mg/m i.v. on days 2 to 4), mitoxantrone (10 mg/m i.v. on day 2), and rituximab (375 mg/m i.v. on day 1), for up to six cycles every 28 days. All patients achieved a complete remission, a median of four cycles was given. Treatment-related toxicities were mainly hematologic, with grade 3-4 neutropenia observed in 11/13 patients (84.6%). One patient had grade 3 febrile neutropenia, two patients developed prolonged pancytopenia (15%), and one patient experienced CMV reactivation at 2 months. After a median follow-up of 84 months, 1/13 had disease relapse and received total gastrectomy; estimated 10-year progression-free survival and overall survival were 92.4 and 100%, respectively. Our study suggests R-FM regimen has a high long-term efficacy for untreated HP-negative gastric MALT lymphoma patients and HP-positive patients who failed HP eradication. The elevated incidence of grade 3-4 hematological toxicity, yet manageable, makes this treatment less safe compared to rituximab in combination with chlorambucil or bendamustine.

摘要

对于幽门螺杆菌(HP)阴性的胃黏膜相关淋巴组织(MALT)淋巴瘤患者或根除HP后仍有持续性疾病的患者,最佳治疗方案尚无共识。我们研究了氟达拉滨、米托蒽醌联合利妥昔单抗(R-FM)作为一线治疗方案。分析了一组13例患者。诱导治疗包括氟达拉滨(第2至4天静脉注射25mg/m²)、米托蒽醌(第2天静脉注射10mg/m²)和利妥昔单抗(第1天静脉注射375mg/m²),每28天进行多达六个周期的治疗。所有患者均实现完全缓解,中位给予四个周期的治疗。治疗相关毒性主要为血液学毒性,11/13例患者(84.6%)出现3-4级中性粒细胞减少。1例患者出现3级发热性中性粒细胞减少,2例患者出现长期全血细胞减少(15%),1例患者在2个月时出现巨细胞病毒再激活。中位随访84个月后,1/13例患者疾病复发并接受了全胃切除术;估计10年无进展生存率和总生存率分别为92.4%和100%。我们的研究表明,R-FM方案对未经治疗的HP阴性胃MALT淋巴瘤患者和根除HP失败的HP阳性患者具有较高的长期疗效。3-4级血液学毒性发生率升高,但可控制,与利妥昔单抗联合苯丁酸氮芥或苯达莫司汀相比,这种治疗的安全性较低。

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