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苯达莫司汀预处理后自体造血干细胞移植(ASCT):LYmphoma Study Association(LYSA)中心 474 例患者的法国多中心研究结果。

Bendamustine-based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers.

机构信息

Institut d'Hématologie de Basse-Normandie, CHU, Caen, France.

Department of Hematology, Institut Paoli Calmettes, Marseille.

出版信息

Am J Hematol. 2018 Jun;93(6):729-735. doi: 10.1002/ajh.25077. Epub 2018 Mar 14.

DOI:10.1002/ajh.25077
PMID:29473209
Abstract

Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.

摘要

卡莫司汀短缺导致在接受自体干细胞移植治疗淋巴瘤(包括苯达莫司汀为基础的[BeEAM])之前,更多地使用替代预处理方案。本研究旨在评估 BeEAM 方案在大量患者中的安全性。共分析了 474 例中位年龄为 56 岁的患者。大多数患者患有弥漫性大 B 细胞淋巴瘤(43.5%)。苯达莫司汀在第-7 天和第-6 天的中位剂量为 197mg/m /天(50-250)。观察到的 1-4 级毒性包括黏膜炎(83.5%)、胃肠炎(53%)、皮肤毒性(34%)、结肠炎(29%)、肝毒性(19%)、肺炎(5%)和心律失常(4%)。报告了 3.3%的患者发生非复发死亡率(NRM)。报告了 132 例(27.9%)急性肾衰竭(ARF)(G ≥2;12.3%)。预处理后发生肾衰竭的患者器官毒性和死亡更为频繁。在多变量分析中,移植前慢性肾衰竭、苯达莫司汀剂量>160mg/m 和年龄是 ARF 的独立预后因素。移植前慢性肾衰竭、水化体积、水化持续时间和依托泊苷剂量是 NRM 的预测因素。一个简单的四点评分系统可以根据 ARF 的风险水平对患者进行分层,并可能减少苯达莫司汀的剂量以避免毒性。药物短缺可能会产生危险的后果。需要前瞻性、对照研究来证实与其他类型的高剂量治疗相比,这种预处理方案的毒性/疗效范围。

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