High-Dose Melphalan and Autologous Stem Cell Transplantation In AL Amyloidosis and Monoclonal Immunoglobulin Deposition Disease Associated End-Stage Renal Disease Requiring Dialysis
Authors: Sanchorawala Vaishali , Quillen Karen , Finn Kathleen T , Andrea Nancy T , Sloan J. Mark , Dember Laura , Segal Adam , Doros Gheorghe , Skinner Martha , Seldin David 
Published: October 2019

Abstract
Abstract 3553
Treatment of AL amyloidosis (AL) and monoclonal immunoglobulin deposition disease (MIDD) with high dose melphalan and autologous stem cell transplant (HDM/SCT) offers a high rate of durable complete hematologic responses and leads to clinical responses and improvement in survival. The development of end-stage renal disease (ESRD) is common among patients with AL amyloidosis and MIDD-associated renal disease leading to requirement for renal replacement therapy. Because of toxicity associated with HDM/SCT, there has been concern about its safety in patients with ESRD Therefore the role of HDM/SCT for patients with renal insufficiency has been called into question. Here we report on standard operating procedure, toxicities, hematologic responses and survival of patients with ESRD treated with HDM/SCT for AL amyloidosis and MIDD. Between 7/1994 and 6/2010, 32 patients with AL amyloidosis and 4 patients with MIDD associated ESRD were treated with HDM/SCT. The median age was 53 (range, 28–68). There were 21 (58%) males and 18 (50%) with kappa clonal plasma cell dyscrasia. Organ involvement distribution was typical for this disease: 75% patients (n=27) had 2 or more organs involved; 25% (n=9) had only renal involvement and 28% (n=10) had symptomatic cardiac involvement. The median duration of dialysis-dependence prior to HDM/SCT was 3.4 months and the median time from diagnosis to HDM/SCT was 6.5 months. Peripheral blood stem cells were mobilized using G-CSF alone at 10–16 m/kg/day for 3–4 days. Melphalan was administered intravenously in divided doses on 2 consecutive days. Oral cryotherapy was administered during and 15 minutes before and after infusion of melphalan since 2/2002 to reduce the incidence and severity of mucositis. The total dose of melphalan ranged from 100–200 mg/m2, depending on age, severity of cardiac disease and performance status. Stem cells were infused 24–72 hours after completion of melphalan. Hemodialysis patients were dialyzed according to the patient's usual schedule but with an interval of at least 2 hours between the administration of melphalan or infusion of stem cells and the initiation of hemodialysis. An extra session of hemodialysis was performed either on the second day of melphalan infusion and/or the day of stem cell infusion. Peritoneal dialysis exchanges were performed according to the patient's usual schedule. Antimicrobial prophylaxis with an oral quinolone, acyclovir and fluconazole was started on D + 1. Five patients received peritoneal dialysis and the remainder received hemodialysis. Thirty-one % (n=11) received 200 mg/m2 HDM, 47% (n=17) 140 mg/m2 HDM and 22% (n=8) 100 mg/m2 HDM. Treatment-related mortality, defined as deaths within 100 days of SCT, occurred in 6% (n=2/36). There were no deaths during stem cell mobilization and collection or stem cell infusion. There were additional 7 deaths (19%) during the first year after HDM/SCT. Hematologic response was assessed at 1 year following HDM/SCT. Hematologic complete response (CR) was defined as absence of monoclonal gammopathy by serum and urine by IFE, absence of clonal plasma cells in the bone marrow, and normalization of serum free light chain concentration and ratio since 2003. CR occurred in 70% (n=19) of 27 surviving patients at 1 year following HDM/SCT. The median time to neutrophil and platelet engraftment was 10 and 14 days, respectively. The median number of red cell and platelet transfusion was 4 units and 6 packs, respectively. Thirteen (36%) patients developed grade 3 or 4 mucositis. Of note, 45% (n=10/22) developed grade 3 or 4 mucositis before institution of oral cryotherapy compared to 14% (n=2/14) after its initiation (p=0.07). The median survival for the entire group of 36 patients is 64 months (5.3 years) from the time of SCT. The median survival is 62 months from the time of initiation of dialysis. The median survival is 74 months (6.1 years) for the patients achieving a CR compared to 38 months (3.1 years) for those not achieving a CR (p=0.439). Nine patients with hematologic CR have either undergone or are awaiting renal transplantation. In conclusion, HDM/SCT is an effective treatment in selected patients with AL amyloidosis or MIDD associated ESRD with treatment-related morbidity and mortality and outcomes similar to those for non-dialysis patients.

Disclosures:
No relevant conflicts of interest to declare.