Lee S Y, Meehan R S, Seldin D C, Sloan J M, Quillen K, Shelton A, Brauneis D, Sanchorawala V
Amyloidosis Center, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.
Section of Hematology/Oncology, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA.
Bone Marrow Transplant. 2016 Oct;51(10):1318-1322. doi: 10.1038/bmt.2016.132. Epub 2016 May 16.
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.
大剂量美法仑联合干细胞移植(HDM/SCT)可延长轻链(AL)淀粉样变性患者的生存期,并诱导血液学和临床反应。美法仑80%与血浆蛋白结合(60%与白蛋白结合)。我们推测,严重低白蛋白血症患者的游离美法仑比例更高,毒性更大。对2011年至2014年间接受HDM/SCT治疗且患有严重低白蛋白血症(SH)(定义为血清白蛋白⩽2 g/dL)的AL淀粉样变性患者进行了回顾性研究。确定了16例SH患者。2011年至2012年间接受治疗的41例无严重低白蛋白血症(WSH)患者作为对照。SH患者中需要血液透析的急性肾衰竭发生率为25%,而WSH患者中为5%(P = 0.05)。并非所有需要透析的患者都需要长期透析;SH患者为6.25%,WSH患者为2.44%(P = 0.49)。两组之间3级或4级发热性中性粒细胞减少症和胃肠道毒性的发生率无显著差异。两组的植入动力学相似。接受HDM/SCT治疗AL淀粉样变性的SH患者中,4级肾毒性和3级头晕更为常见。有必要对SH患者肾毒性增加的机制进行进一步研究。