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

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 sche...

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Main Authors: Rabea Mecklenbrauck, Bernhard M.W. Schmidt, Heike Bähre, Annamaria Brioli, Arnold Ganser, Florian H. Heidel, Felicitas Thol
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Leukemia Research Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S221304892500024X
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author Rabea Mecklenbrauck
Bernhard M.W. Schmidt
Heike Bähre
Annamaria Brioli
Arnold Ganser
Florian H. Heidel
Felicitas Thol
author_facet Rabea Mecklenbrauck
Bernhard M.W. Schmidt
Heike Bähre
Annamaria Brioli
Arnold Ganser
Florian H. Heidel
Felicitas Thol
author_sort Rabea Mecklenbrauck
collection DOAJ
description 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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spelling doaj-art-fb7f36df66cf4e8c9b013266d2956ca92025-08-20T03:30:02ZengElsevierLeukemia Research Reports2213-04892025-01-012410052210.1016/j.lrr.2025.100522Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myelomaRabea Mecklenbrauck0Bernhard M.W. Schmidt1Heike Bähre2Annamaria Brioli3Arnold Ganser4Florian H. Heidel5Felicitas Thol6Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Correspondence author: Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital Headley Way, OX3 9DS, Oxford, United Kingdom.Department of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyZFA Metabolomics, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Cellular Therapy Center (CTC), Hannover Medical School, Hannover, GermanyDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyHigh-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.http://www.sciencedirect.com/science/article/pii/S221304892500024XMultiple myelomaAutologous stem cell transplantationHigh-dose melphalanHemodialysis
spellingShingle Rabea Mecklenbrauck
Bernhard M.W. Schmidt
Heike Bähre
Annamaria Brioli
Arnold Ganser
Florian H. Heidel
Felicitas Thol
Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma
Leukemia Research Reports
Multiple myeloma
Autologous stem cell transplantation
High-dose melphalan
Hemodialysis
title Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma
title_full Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma
title_fullStr Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma
title_full_unstemmed Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma
title_short Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma
title_sort pharmacokinetics and outcome of high dose melphalan followed by autologous stem cell transplantation in dialysis dependent patients with multiple myeloma
topic Multiple myeloma
Autologous stem cell transplantation
High-dose melphalan
Hemodialysis
url http://www.sciencedirect.com/science/article/pii/S221304892500024X
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