High-Dose Melphalan and Stem Cell Transplantation in Patients on Dialysis Due to Immunoglobulin Light-Chain Amyloidosis and Monoclonal Immunoglobulin Deposition Disease

Abstract

The kidney is the most common organ affected by immunoglobulin light-chain (AL) amyloidosis and monoclonal immunoglobulin deposition disease (MIDD), often leading to end-stage renal disease (ESRD). High-dose melphalan and stem cell transplantation (HDM/SCT) is effective for selected patients with AL amyloidosis, with high rates of complete hematologic response and potential for improved organ dysfunction. Data on tolerability and response to HDM/SCT in patients with ESRD due to AL amyloidosis and MIDD are limited. We analyzed data on toxicity, efficacy, and hematologic and renal response of HDM/SCT in 32 patients with AL amyloidosis and 4 patients with MIDD who were dialysis-dependent for ESRD treated at Boston Medical Center between 1994 and 2016. The most common grade 3/4 nonhematologic toxicities were infections (75%), metabolic abnormalities (56%), mucositis (42%), constitutional symptoms (39%), pulmonary complications (39%), and diarrhea (28%). Treatment related mortality (defined as death within 100 days of SCT) occurred in 8% (3 of 36). A complete hematologic response was achieved in 70% of evaluable patients (19 of 27) at 1 year after HDM/SCT. In the entire cohort, median overall survival (OS) after HDM/SCT was 5.8 years; median OS was 1 year for those who did not achieve a complete hematologic response and 8 years for those who did achieve a complete hematologic response. Twelve patients (33%) underwent kidney transplantation after successful treatment with HDM/SCT at a median of 2.4 years after SCT. HDM/SCT is safe and effective in inducing hematologic complete responses and prolonging survival in patients with ESRD from AL amyloidosis and MIDD. Achievement of a durable hematologic response can make these patients possible candidates for renal transplantation.

Systemic immunoglobulin light chain amyloidosis

“…Eligibility criteria for HDM/SCT vary between centers, but broadly require a confirmed tissue diagnosis of amyloidosis, clear evidence of a clonal plasma or B cell dyscrasia, and adequate measures of performance status (a grade of 0-2 at the ECOG performance status), cardiac function (a left ventricular ejection fraction of >40%, cardiac biomarkers below the thresholds, NewYork Heart Association class of <3), pulmonary function (O2 saturation >95% on room air), hepatic function (total bilirubin level <2 mg/dL) and hemodynamic stability (baseline systolic blood pressure >90 mm Hg). Patients on hemodialysis or peritoneal dialysis are not excluded at some centers if other eligibility criteria are met 89.…”

Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

“…In the context of renal impairment, certain drugs are preferred, such as cyclophosphamide and bortezomib that are better tolerated than melphalan and lenalidomide. Despite a limited response to melphalan and prednisone in light-chain deposition disease [48], a case series of four dialysis-dependent MIDD patients reported that high-dose melphalan followed by autologous stem cell transplant to be a safe and effective option that resulted in durable responses and subsequently allowed patients to receive a kidney transplant [49]. Many patients who develop end-stage renal impairment are often not considered for kidney transplantation due to their high rate of recurrence, as eradication of the underlying B-cell clone is not frequently possible [36][37][38].…”

High-Dose Melphalan and Autologous Peripheral Blood Stem Cell Transplantation in AL Amyloidosis

“…Risk factors for AKI included higher urine protein excretion, lower creatinine clearance at baseline, cardiac involvement, higher melphalan dose, and development of bacteremia during SCT [45]. HDM/SCT can also be safely and cautiously performed in patients with end-stage renal disease on dialysis and inducing durable hematologic responses then can make patients eligible for renal transplantation [46].…”