Plasma Cell Disorders

Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis

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Abstract

High-dose melphalan with stem cell transplantation (HDM/SCT) extends survival and induces hematologic and clinical responses in patients with light chain (AL) amyloidosis. Eighty percent of melphalan is bound to plasma proteins (60% albumin-bound). We hypothesized that patients with profound hypoalbuminemia have a greater free melphalan fraction and more toxicity. Patients with AL amyloidosis treated with HDM/SCT between 2011 and 2014 with severe hypoalbuminemia (SH), defined as serum albumin 2 g/dL were studied retrospectively. Sixteen patients with SH were identified. Forty-one patients without severe hypoalbuminemia (WSH) treated between 2011 and 2012 served as control. The incidence of acute renal failure requiring hemodialysis was 25% among patients with SH, compared with 5% among patients WSH (P=0.05). Not all patients who needed dialysis required it long term; 6.25% for SH and 2.44% for WSH (P=0.49). The rates of grade 3 or 4 febrile neutropenia and gastrointestinal toxicities were not significantly different between the groups. Engraftment kinetics were similar for both groups. Grade 4 renal toxicity and grade 3 lightheadedness were more frequent in patients with SH undergoing HDM/SCT for AL amyloidosis. Further studies into the mechanism of increased renal toxicity in patients with SH are warranted.

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Acknowledgements

We gratefully acknowledge our colleagues in the Amyloidosis Center at the Boston University School of Medicine, and the Clinical Trials Office and staff of the Solomont Center for Cancer and Blood Disorders at Boston Medical Center who assisted with the multidisciplinary evaluation and treatment of these patients with amyloidosis.

Author contributions

SYL and RSM collected and analyzed data, performed research and wrote the manuscript. DCS designed and performed research and edited manuscript. JMS, KQ, AS and DB performed research and edited manuscript. VS designed research, performed research, analyzed data and wrote the manuscript.

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Correspondence to V Sanchorawala.

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The authors declare no conflict of interest.

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