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

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports Pub Date : 2025-01-01 DOI:10.1016/j.lrr.2025.100522

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

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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 (p = 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 (p = 0.9). Overall survival both from d₀ of ASCT and diagnosis was comparable (p = 0.33 and p = 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.

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高剂量美伐兰后自体干细胞移植治疗依赖透析的多发性骨髓瘤患者的药代动力学和疗效

高剂量美法兰后自体干细胞移植（ASCT）仍然是适合多发性骨髓瘤（MM）患者的标准治疗方法。然而，依赖血液透析的个体经常被排除在ASCT之外。关于化疗剂量和血液透析计划的建议在文献中有所不同，并且由于队列的异质性，明确的结论受到阻碍。我们的目的是评估ASCT在MM和终末期肾病患者中的安全性和有效性，并在固定时间表的美伐兰输注和血液透析中检查美伐兰的药代动力学。回顾性分析了2000年至2022年间13例接受ASCT同时进行血液透析的患者的结果，并与匹配的不进行血液透析的患者进行了比较。测定4例血液透析依赖患者和5例血液透析独立患者的血浆浓度。在美法兰输注和血液透析间隔6小时时，血液透析依赖患者的血药浓度与血液透析独立患者相当（p = 0.9）。高剂量美法兰的即时副作用率在13名透析依赖患者中显著高于47名匹配对照，尽管没有长期中性粒细胞减少症（p = 0.9）。ASCT 0和诊断的总生存率相当（p = 0.33和p = 0.17）。因此，采用建议的时间表和即时副作用的管理使ASCT成为骨髓瘤终末期肾脏疾病患者的安全选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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