Long-term results of a risk-adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis

Background and Objectives. High-dose melphalan with autologous peripheral blood stem cell transplantation (ASCT) is an effective treatment for systemic primary amyloidosis. This procedure is, however, associated with substantial toxicity and mortality, particularly if the heart is involved. Refined selection of patients suitable for transplantation and personalized adaptation of the doses of melphalan might improve the outcome. Design and Methods. Twenty-two consecutive patients were selected for age, number of organ systems involved, heart and kidney function, and treated with risk-adapted melphalan conditioning. This was first-line therapy in 81% of cases. Results. Fifty-five percent of the patients had amyloid involvement of two organ systems, with renal involvement predominant in half. Approximately 70% received full-dose melphalan. Toxicity was manageable and three transplant-related deaths (14%) occurred only in the early phase of the study. The median overall survival was 68 months. The intent-to-treat hematologic response rate was 55% at +12 months (complete, 36%; partial, 19%), which was accompanied by organ responses in 75%. Survival was positively influenced by: (i) hematologic response at +3 months (complete+partial responses 55%, median not reached, more than 108 months; no response, median 17 months) (p=0.001); (ii) amyloid involvement of a single organ system (p=0.016). Prolonged follow-up demonstrated that remissions are durable, but relapses may occur as 4 of 12 responsive patients (33%) relapsed, three from complete response, between +30 to +38 months. Interpretation and Conclusions. The present risk-adapted approach produced acceptable toxicity and peri-transplant mortality with prolonged survival in responsive patients. Additional therapy should be considered if no hematologic response is observed at +3 months after ASCT.