High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution

Abstract

Treatment with high-dose melphalan chemotherapy supported by hematopoietic rescue with autologous stem cells produces high rates of hematologic responses and improvement in survival and organ function for patients with AL amyloidosis. Ongoing clinical trials explore pre-transplant induction regimens, post-transplant consolidation or maintenance approaches, and compare transplant to non-transplant regimens. To put these studies into context, we reviewed our recent experience with transplant for AL amyloidosis in the Amyloid Treatment and Research Program at Boston Medical Center and Boston University School of Medicine. Over the past 10 years, there was a steady reduction in rates of treatment-related mortality and improvement in 1-year survival, now approximately 5% and 90%, respectively, based upon an intention-to-treat analysis. Median overall survival of patients treated with this approach at our center exceeds 7.5 years.

Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience

“…19 However, patients with GI amyloidosis and evidence of active GI bleeding or ulceration were not offered myeloablative chemotherapy, because of the risk of catastrophic GI hemorrhage ( Figures 3 and 4). 20 In the series we report here, severe GI bleeding a.J. occurred in only 6% of patients treated with HDM/SCT, which is comparable to rates of GI hemorrhage in other reported transplant series.…”

Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group

“…Data from large, tertiary‐referral transplant centres have shown haematological response rates as high as 76% with HDM/ASCT, with CR in up to 39% of cases . Organ response rates range from 47–63% with treatment‐related mortality (TRM) rates of 10–12%, and more recently, as low as 5% . Extended follow‐up confirms the survival benefit of a complete response, with median survival of 13.2 years in these patients compared with 3.2 years in those who fail to achieve a CR …”

“…It is clear from these studies that patients who do not undergo therapy to eradicate the plasma cell clone following transplantation will develop amyloid involvement and failure of the graft. Studies from various centres where cardiac transplantation has been combined with effective anti‐plasma cell chemotherapy have reported 1‐year overall survival around 80% with survival at 5 years dropping to around 60%, most often due to recurrent multi‐organ amyloidosis …”

“…Studies from various centres where cardiac transplantation has been combined with effective anti-plasma cell chemotherapy have reported 1-year overall survival around 80% with survival at 5 years dropping to around 60%, most often due to recurrent multi-organ amyloidosis. 37,52…”

Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis

“…5 However, this study had serious patient selection issues insofar as the treatment-related mortality associated with transplant was 24%, making it nearly impossible to show any benefit from the technique. The acceptable treatment-related mortality for transplant at one point was 10-15%, 6 although studies have shown mortality rates of 40%. 7 A high mortality rate with SCT is no longer acceptable because lower-risk alternatives, including lenalidomide-based 8,9 and bortezomib-based 10 therapies, have been introduced, with much lower immediate risk to patients.…”