Cardiac Followed by Autologous Stem Cell Transplantation for Systemic AL Amyloidosis.
Authors: Gillmore J. D. , Wechalekar A. D. , Goodmam H. J.B. , Lachmann H. J. , Offer M. , Joshi J. , Hawkins P. N. 
Published: April 2020

Abstract
The prognosis for AL amyloidosis with conventional treatment is very poor. Treatment with high dose melphalan with stem cell rescue (SCT) may offer the best chance of haematological remission and arresting amyloid accumulation. However, patients with significant clinically apparent cardiac amyloid are not eligible for SCT due to unacceptably high treatment-related mortality. Cardiac transplantation is controversial due to the systemic and progressive nature of the disease. We report the UK experience of this combined approach in patients with predominant cardiac AL amyloidosis. Cardiac transplantation followed by SCT was undertaken in 5 patients with histologically confirmed AL amyloidosis who presented to the UK National Amyloidosis Centre. Cardiac assessment included clinical evaluation, ECG and echocardiographic studies, and measurement of NT-proBNP (retrospectively). The median age at diagnosis of amyloid was 53 years (range 38–59). The median time from diagnosis to cardiac transplantation was 4 months (range 2–9). All patients had NYHA class IV heart failure and advanced cardiac amyloidosis by echocardiographic criteria. There was no evidence of extra-cardiac amyloid related organ dysfunction. Median interventricular septal (IVS) and left ventricular posterior wall (LVPW) thicknesses were 17 mm (IVS range 15–19, LVPW range 15–18). 4 patients had a conventionally detectable serum M protein, 3 had light chains in the urine while all had abnormal serum free light chains (sFLC) (kappa light chain excess in 2 and lambda light chain excess in 3). 2/5 patients received melphalan 25mg/m2 prior to cardiac transplant. The cardiac transplant was uncomplicated in 3 patients while 1 had a single episode to tonic clonic seizures (cyclosporine induced) and 1 had reversible acute renal failure (ARF) with a median post operative stay of 24 days (range 14–30). Acute rejection occurred on a single occasion in 2 patients (ISHLT grade 2 or 3A) and responded to intravenous methylprednisolone. The median time from cardiac transplantation to SCT was 13 months (range 10–24). At the time of SCT, there was no echocardiographically detectable amyloid in any of the cardiac grafts though all patients had clinical and/or SAP scintigraphic evidence of progressive extra-cardiac amyloid. All patients received melphalan 140mg/m2 as transplant conditioning. The post transplant course was complicated by a liposomal amphoterecin responsive fungal chest infection and ARF in 1 patient each. None of the patients had any cardiac problems during the SCT. 4/5 patients had a ≥50% reduction in serum free light chain production. The median follow-up is now 95 (range, 37–118) and 90 (range, 33–114) months from diagnosis of amyloidosis and cardiac transplantation respectively. Three of 5 patients are alive, in haematological remission with no evidence of intra or extra-cardiac amyloid accumulation. Median overall survival by Kaplan-Meier estimate has not been reached. Of the 2 patients who died, 1 patient had a poor response to SCT while the other patient relapsed 80 months post SCT. Both had progressive amyloid deposition including echocardiographic evidence of amyloid in the transplanted heart. In summary, cardiac transplantation followed by SCT is feasible in carefully selected patients with predominantly cardiac AL amyloidosis and may be associated with prolonged survival.