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透析依赖型多发性骨髓瘤患者大剂量美法仑后自体干细胞移植的药代动力学及疗效

Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma.

作者信息

Mecklenbrauck Rabea, Schmidt Bernhard M W, Bähre Heike, Brioli Annamaria, Ganser Arnold, Heidel Florian H, Thol Felicitas

机构信息

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.

出版信息

Leuk Res Rep. 2025 Jun 19;24:100522. doi: 10.1016/j.lrr.2025.100522. eCollection 2025.

Abstract

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for fit patients with multiple myeloma (MM). However, individuals who are dependent on hemodialysis are frequently excluded from ASCT. Recommendations on chemotherapy dosing and hemodialysis scheduling vary in literature and definite conclusions are impeded by the heterogeneity of cohorts. We aimed to evaluate the safety and efficacy of ASCT in patients with MM and end-stage renal disease and to examine the pharmacokinetics of melphalan on a fixed schedule of melphalan infusion and hemodialysis. The outcome of 13 patients undergoing ASCT while being on hemodialysis between 2000 and 2022 was retrospectively analysed and compared to matched hemodialysis-independent patients. Melphalan plasma concentrations were measured in 4 hemodialysis-dependent and 5 independent patients. Plasma concentrations of hemodialysis-dependent patients were comparable to hemodialysis-independent patients with a 6-hour interval between melphalan infusion and hemodialysis ( = 0.9). The rate of immediate side effects of high-dose melphalan was significantly higher in 13 dialysis-dependent patients compared to 47 matched controls despite not having prolonged neutropenia ( = 0.9). Overall survival both from d of ASCT and diagnosis was comparable ( = 0.33 and = 0.17, respectively). Thus, adopting the proposed schedule and management of immediate side effects make ASCT a safe option for myeloma patients with end-stage renal disease.

摘要

大剂量美法仑序贯自体干细胞移植(ASCT)仍是适合的多发性骨髓瘤(MM)患者的标准治疗方案。然而,依赖血液透析的个体通常被排除在ASCT之外。关于化疗剂量和血液透析安排的建议在文献中各不相同,队列的异质性阻碍了得出明确结论。我们旨在评估ASCT在MM合并终末期肾病患者中的安全性和有效性,并在固定的美法仑输注和血液透析时间表下研究美法仑的药代动力学。回顾性分析了2000年至2022年间13例在进行血液透析时接受ASCT的患者的结果,并与匹配的非血液透析依赖患者进行比较。在4例血液透析依赖患者和5例非依赖患者中测量了美法仑血浆浓度。美法仑输注与血液透析间隔6小时的情况下,血液透析依赖患者的血浆浓度与非血液透析依赖患者相当(P = 0.9)。13例透析依赖患者中高剂量美法仑的即刻副作用发生率显著高于47例匹配对照,尽管没有长期中性粒细胞减少(P = 0.9)。从ASCT当天和诊断时起的总生存率相当(分别为P = 0.33和P = 0.17)。因此,采用建议的时间表和即刻副作用管理方法使ASCT成为MM合并终末期肾病患者的安全选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/12264629/d3e00abea18a/gr1.jpg

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