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在资源有限的国家,药物短缺对淋巴瘤患者自体造血细胞移植中四种不同预处理方案的早期毒性和疗效的影响。

Early Toxicity and Efficacy of Four Different Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Patients With Lymphoma: Impact of Drug Shortages in a Resource-Constrained Country.

机构信息

Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; Servicio de Hematología y Hemoterapía, Hospital Vozandes, Quito, Ecuador.

Laboratório de Investigação Médica (LIM) 31, Universidade de São Paulo, São Paulo, Brazil; Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; Hospital Vila Nova Star-Rede D'Or, São Paulo, Brazil.

出版信息

Transplant Cell Ther. 2024 Oct;30(10):1003.e1-1003.e9. doi: 10.1016/j.jtct.2024.07.025. Epub 2024 Aug 2.

Abstract

High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.

摘要

高剂量化疗后自体造血细胞移植(AHCT)仍然是一部分复发或难治性(R/R)淋巴瘤患者可行的巩固治疗策略。BEAM(卡莫司汀、依托泊苷、阿糖胞苷和马法兰)由于其令人满意的疗效和耐受性而被广泛认为是主要的预处理方案。然而,卡莫司汀和马法兰的短缺迫使临床医生探索替代预处理方案。本研究旨在比较 BEAM、CBV(卡莫司汀、依托泊苷、环磷酰胺)、BuMel(白消安、马法兰)和 BendaEAM(苯达莫司汀、依托泊苷、阿糖胞苷、马法兰)预处理后患者的毒性和移植结局。我们回顾性分析了 2014 年至 2020 年间 213 例 R/R 淋巴瘤患者接受 AHCT 的数据(CBV 65 例、BuMel 42 例、BEAM 68 例、BendaEAM 38 例)。基于预处理类型,采用多变量模型评估毒性和移植结局。在 III 级至 IV 级毒性中,BuMel(45%)和 BendaEAM(24%)的口腔黏膜炎发生率高于 BEAM(15%)和 CBV(6%)(P ≤.001)。BendaEAM(42%)腹泻更为常见,而 BuMel(7%)腹泻较少(P =.01)。急性肾损伤仅发生在 BendaEAM 后(11%)。BendaEAM 后发热性中性粒细胞减少和感染并发症更为常见。根据预处理类型,其他治疗相关毒性的发生率没有显著差异。BendaEAM(比值比 [OR] 3.07,P =.014)和 BuMel(OR 4.27,P =.002)与 D+100 时更高的 III 级至 IV 级毒性独立相关。然而,四种方案之间在复发/进展、非复发死亡率、无进展生存期或总生存期方面没有显著差异。BuMel 和 BendaEAM 与更高的 III 级至 IV 级毒性相关。基于卡莫司汀的方案似乎毒性更小、更安全;然而,移植结局没有显著差异。由于药物短缺而使用替代预处理方案可能会导致淋巴瘤患者接受 AHCT 后毒性增加。

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