Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

Abstract

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

AL amyloidosis is a systemic disorder, caused by a monoclonal light chains (LC) producing clonal dyscrasia, that mainly affects the kidneys, heart, liver, and peripheral and autonomic nervous systems.1,2 Restrictive cardiomyopathy is a severe and common manifestation of AL amyloidosis, associated with a median survival of approximately 9 months and less than 6 months once congestive heart failure is present.3

Cardiac transplantation in AL amyloidosis3–10 remains controversial, because of organ shortage, recurrence of amyloid in the graft, and progression of systemic deposits. Encouraging results were recently obtained in few cases of AL amyloid cardiomyopathy, with sequential heart transplantation followed by high dose melphalan (HDM) therapy and autologous stem cell transplantation (ASCT). Providing remission of the underlying plasma cell disorder is achieved by HDM/ASCT, amyloid deposits do not recur in the allograft and extra-cardiac disease progression is halted, resulting in prolonged survival.10 However, because of high treatment–related mortality associated with HDM/ASCT, this procedure is applicable only to selected cases. We report here a patient with systemic AL amyloidosis with congestive heart failure and multiple organ involvement, whose condition dramatically improved after cardiac transplantation following sustained clonal remission induced by melphalan plus dexamethasone.