Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience

Abstract

Summary:Recent reports from large amyloidosis referral centers suggest that primary systemic AL amyloidosis patients treated with high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) survive longer than historical controls treated with less intensive chemotherapy, despite high transplant-related mortality (TRM) rates of 410%. A retrospective review was conducted to determine if the outcome of ASCT for AL amyloidosis at our institution was similar to that reported at major amyloidosis referral centers. Over a 7 year period, we treated a total of 15 AL amyloidosis patients with ASCT, including four with poor prognosis cardiac or multisystem involvement. No TRM was observed. Overall, 10 patients (67%) achieved a complete hematological response and four patients (27%) achieved a complete organ response. The 4-year event-free and overall survival rates were 60% (95% CI 32-89%) and 75% (95% CI 50-100%), respectively. One patient, who presented with cardiac failure and multiorgan involvement with colonic bleeding currently remains in complete remission 62 months post-ASCT. In conclusion, ASCT for primary AL amyloidosis can safely be performed at experienced transplant centers that are not associated with major amyloidosis referral centers, and is feasible for patients who have multisystem involvement, particularly for motivated patients with good performance status. In primary systemic AL amyloidosis, amyloid fibrils derived from monoclonal immunoglobulin light chains are produced by an underlying clonal plasma cell dyscrasia.These amyloid fibrils accumulate in vital organs, leading to progressive organ dysfunction, physical debility and death. The median survival of untreated patients is 10-14 months, while that of patients with cardiomyopathy and congestive heart failure is generally less than 6 months.1,2 Conventional chemotherapy with melphalan and prednisone produces response rates between 20 and 30%, median survival times of 12-18 months, and 5-year survival rates of 15%. 3-5High-dose melphalan (HDM) with autologous peripheral stem cell transplantation (ASCT) is a promising therapeutic option which initially demonstrated hematological response rates of 62% and organ response rates as high as 44% in small series.6,7 Unfortunately, reported transplant-related mortality (TRM) rates are high, between 15 and 43%.7-10 Therefore, prognostic variables were analyzed in an attempt to better select patients and reduce TRM. Patients with poor performance status, symptomatic cardiac involvement, or involvement of greater than two organs tended to have increased TRM and were considered poor candidates for ASCT.6-12 Although HDM/ASCT seems to produce higher response and survival rates than conventional chemotherapy, criteria for selecting patients for ASCT are still not firmly established. [12][13][14][15] Owing to the high TRM of HDM/ASCT for primary systemic AL amyloidosis, it may be possible that the results of this form of aggressive therapy are better when administered at tertiary referral centers that...

Transplantation for amyloidosis

“…In our cohort of 270 patients, the mortality rate on day 100 was 11%; this compares favorably with other institutions that reported mortality rates as high as 40% [11][12][13]. A low mortality rate is necessary to compare stem cell transplantation with conventional chemotherapy when using survival as an endpoint.…”

Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation

“…Untreated, the prognosis of patients with advanced amyloidosis is grim. Treatment with high-dose chemotherapy and HCT may reverse the amyloid-related disease (Skinner et al, 2004;Chow et al, 2005), however, the benefit of HCT is still controversial (Jaccard et al, 2007;Kumar et al, 2008). Compared to multiple myeloma, where the transplant-related mortality is <2%, mortality rates for transplantation in patients with amyloidosis ranges from 11% to 25%.…”

Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients

“…6 Single and multicenter studies show CR rates of 16%-67%, organ responses in 25%-45% of patients, and a median overall survival (OS) of ϳ 5 years. [7][8][9][10][11][12][13][14][15][16] A case-control study demonstrated the benefit of this procedure for patients younger than 70 years compared with nontransplant regimens, most of them alkylator-based oral chemotherapy. 17 A major issue in HDM/SCT for AL amyloidosis is the potential for high treatment-related mortality (TRM) because of underlying organ dysfunction in this disease.…”