Cardiac Transplant Followed by High-Dose Melphalan and Autologous Stem Cell Transplantation (ASCT) for Patients with AL Amyloidosis and Severe Heart Failure.
Authors: Dey Bimalangshu R. , Spitzer Thomas R. , MacGillivray Thomas E. , Chung Stephen S. , Dec G.W. , Seldin David C. , McAfee Steven L. , Ballen Karen , Attar Eyal , Skinner Martha , Madsen Joren C. , Semigran Marc J. 
Published: October 2019

Abstract
Patients with AL amyloidosis who present with severe heart failure due to cardiac amyloidosis rarely survive beyond 6 months. Cardiac transplantation has been used to treat these patients, but survival is markedly reduced (40% at 48 months; Hosenpud et al, Circulation, 1991) due to further progression of systemic amyloidosis, including involvement of the cardiac allograft. ASCT is a standard approach to newly diagnosed AL amyloidosis patients, but this strategy cannot be offered to patients with severe heart failure because of high transplant-related mortality. This led to the development of a treatment plan at Massachusetts General Hospital (listed at clinicaltrials.gov) where the objectives are to evaluate the tolerability and efficacy of sequential cardiac transplant and ASCT. Since Sept. 2000, 24 patients (n=4, diagnosed at MGH; n=20, outside institutions) have been evaluated. Due to contraindications related to the extent of amyloidosis, 7 patients were excluded. Nine patients died prior to cardiac transplant due to lack of a donor. A total of 8 patients underwent cardiac transplant followed by ASCT. All patients (median age, 57 years, range 38–67) had biopsy-proven cardiac AL amyloid; all had a lambda-restricted plasma cell dyscrasia. Patient #4 received combined heart and kidney transplant because of concomitant renal failure. The median time from the diagnosis to cardiac transplant was 6 months (range, 3–10). All 8 patients achieved a target of ≥2×06 CD34+ cells/kg following GCSF stimulation. High-dose melphalan (140–180 mg/m2) and ASCT was performed at a median time of 7 months (range, 4–11) after cardiac transplantation, with Patient #8 currently recovering from ASCT. Patient #3 had a slight increase in serum lambda light chain concentration with marrow plasmacytosis (8% plasma cells) 20 months after ASCT; her plasma cell dyscrasia was stable on thalidomide, but she had sudden death 45 months after cardiac transplant. Patient #5 developed recurrent amyloidosis 11 months following ASCT, and she died of progressive amyloidosis (involving kidneys, liver and lastly cardiac allograft) at 34 months after cardiac transplant. Seven of eight patients have shown no evidence of amyloid in cardiac allograft at any time points. At a median follow-up of 48 months, 6 patients are alive, 7 to 81 months from the time of cardiac transplant, including 5 with no evidence of recurrent amyloidosis who are fully functional [Patient #8 not evaluable yet]. The survival of these patients is comparable to that of 83 patients transplanted at the MGH during the same time who did not have amyloid heart disease (85%, non-amyloid vs. 69%, amyloid at 5 years), in contrast to the survival of 40% at 4 years in amyloid patients who received only cardiac transplant without ASCT (Hosenpud et al). In conclusion, our experience indicates that cardiac transplantation followed by AHSCT is feasible in selected patients with systemic AL amyloidosis who have severe heart failure as their presenting symptoms and that such a sequential transplant strategy may lead to a significant improvement in the quality of life and overall survival.