Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM) Patients with Dialysis-Dependent Renal Failure Is Effective but Carries High Rates of Toxicity.

Abstract

Background: Studies have shown ASCT to be feasible in MM patients (pts) with renal impairment but there are limited data supporting this approach in pts with severe dialysis-dependent renal failure.Patients and Methods: This is a single institution retrospective review of all MM pts who were receiving regular dialysis support at the time of ASCT. Pts with light chain amyloidosis were excluded.Results: From 1998–2006, 22 hemodialysis patients underwent ASCT at our institution. Median age at transplant was 54.3 years (range, 39.4–64.7); 17(77%) pts were male; 17(76%) Salmon Durie stage II–IIIB . MM subtypes: light chains only 9(41%), IgG 8(36%), IgA 4(13%), IgD 2(9%). All pts received high-dose dexamethasone (DEX)-based induction therapy (VAD or DEX alone). High dose therapy consisted of Melphalan (MEL) 200 mg/m2 in 18 pts and MEL 140 mg/m2 in 3 pts. A median of 5.87 X 106 (range, 2.47–51.0) CD34+ cells/kg were collected using cyclophosphamide 2.5 g/m2 + GCSF 10ug/kg/day. Median days to discharge were 19 (range, 14–59). Hematologic toxicity: Of 20 pts with transfusion data available, 14(70%) required RBC and 18(90%) platelet transfusions. Median time to engraftment for neutrophils was 11 days (range, 9–14) and for platelets 13 days (range, 8–17). All patients developed febrile neutropenia. Non-hematologic toxicity (data available in 21 pts): cardiac 13(62%) (arrhythmias, myocardial infarction, CHF), hypotension 6(29%), neurologic 6(29%)(seizure, altered sensorium), infections 6(29%), diarrhea 6(29%), electrolyte imbalances 4(19%) and bleeding 3(14%). Most common grade 3–4 toxicities included mucositis 17(81%), cardiac 12(57%)(most due to atrial arrhythmias), bleeding 3(14%)(epistaxis, hematemesis, tissue hematomas) and infections 3(14%)(CMV, bacteremia, Candidemia). Transplant related mortality (TRM) was 13.6% (3/22) with causes of death including disseminated candidiasis (2) and CMV infection.Responses: Partial responses (PR) were achieved in 18/22 pts. Progression free survival (PFS) from transplant was 22.3 months (95% CI 15–45.6). Three pts (13%) became dialysis-independent (all within 30 days post-transplant). At a median follow-up of 29.6 months (range 0.8–79.6), 10/22 (45%) of patients are alive. Estimated median overall survival from date of transplant was 60 months (95%CI 20.2–79.6) with a 5-year survival probability of 53.2%.Discussion: ASCT in dialysis-dependent MM pts achieves response rates and survival data comparable to that of non-dialysis populations. However, it carries increased toxicity, prolonged median days to discharge (19 days vs. institutional mean of 14 days) and a higher TRM (13.6% vs. institutional mean of 1.6%). The higher rates of cardiac and neurological toxicities enforce the need for pre-transplant identification of pts with co-morbidities, for consideration of dose reduction and risk factor optimization.