Autologous stem cell transplantation for Amyloidosis – pro

Lay Summary: AuSCT is supported by credible evidence for amylod for patients without organ damage.

Treatment for systemic amyloidosis targets the aberrant plasma cell clone to prevent further synthesis and deposition of the amyloid protein. Conventional therapy usually combines oral melphalan with prednisone (MP), shown to yield higher response rates and longer survival than colchicine or prior therapies. Initial results of HDC/AuSCS in uncontrolled patient series were published in 1998. Clinical response rates (50% to 60%) were nearly twice those reported for conventional therapy, and two-year survival reportedly ranged from 56% to 68%. However, two issues tempered initial enthusiasm for these favorable results. First, early series reported procedure-related mortality of 15% to 43%, substantially higher than after HDC/AuSCS for multiple myeloma (less than 5%). Studies that evaluated risk factors for early death identified involvement of more than two organ systems and symptomatic cardiac involvement as significant predictors of treatment-related mortality.
In addition to longer survival, there is evidence suggesting improvement in symptoms and quality of life for amyloidosis patients treated with HDC/AuSCS. Skinner and colleagues reported the largest retrospective series of amyloidosis patients eligible for transplant (n=394). Of the 394 eligible patients, 63 declined treatment and 19 lost eligibility when their disease progressed before treatment started. Estimated median survival for 312 patients who initiated stem-cell mobilization was 4.6 years, but median follow-up was not reported. Of 181 evaluable patients (alive and followed for one year or more), 40% achieved complete hematologic response, defined as no evidence of plasma cell dyscrasia at one year after transplant. They reported functional improvement in at least one affected organ for 44% of evaluable patients: 66% of 73 patients with complete hematologic response and 30% of 108 patients with an incomplete or no hematologic response.

Skinner and colleagues also reported that of 277 patients who completed the transplant protocol, 36 (13%) died of treatment related toxicity before day 100 post-transplant, 21 (8%) died between day 100 and one year, and 39 are alive but had not reached one year since transplant. (13) Note that this series included all patients transplanted between July 1994 and June 2002, of which half (n=196) had three or more organs involved and 43% had some cardiac involvement. Patients with these poor prognostic features likely predominate among the 21% who died within the first year. For example, median survival for those with cardiac involvement (n=137) was significantly shorter (1.6 versus 6.4 years; p=0.001) than for those without cardiac involvement (n=175).

Additional support comes from a registry analysis of 114 amyloidosis patients transplanted between 1995 and 2001 at 50 centers, thus far published only as an abstract. (15) Only 35% of patients reported to the registry were transplanted for initial therapy of amyloidosis, while 25% were transplanted after two years or more prior therapies. With a median follow-up of 29 months after transplant, overall survival at one and three years was 68% and 57%, respectively. Among 77 patients with data available on organ function, investigators reported improvement in 28 (35%). For those with no or one organ involved at transplant, survival at one year was 70%, while for those with two or more organs involved survival at one year was 60%. Survival at one year was also greater for those without cardiac involvement (72% versus 54%). Mortality at 100 days was 25%, but this likely included patients with cardiac and/or multiple organ involvement.

In summary, biologic similarity of the two plasma cell dyscrasias led to inferences that evidence of longer survival after HDC/AuSCS than after conventional-dose therapy in multiple myeloma patients might also be relevant to those with systemic amyloidosis. This hypothesis was questioned based on a retrospective analysis and a simplified matched-pair analysis suggesting similar survival after either therapy for amyloidosis. A subsequent study with more thorough matching of cases and controls reports significantly longer survival after HDC/AuSCS for amyloidosis. Additionally, recent large series and registry analysis report evidence that HDC/AuSCS improves organ function and quality of life. Taken together, these data support the hypothesis that HDC/AuSCS improves outcomes for amyloidosis patients with two or fewer involved organs and without cardiac symptoms. There is recent credible literature to support tandem transplantation. NCCN on AMYL-2 recommends high dose chemotherapy with stem cell transplantation.

Because most patients with amyloidosis are for advanced age, studies of allogeneic transplantation have focused on reduced conditioning regimens. NCCN recommends only autologus stem cell transplant with high dose melphalan conditioning, but also recommend all treatment of whatever kind to be in clinical trials.



NCCN, Amyloidosis, MS-7 2016

Shameem Mahmood, Giovanni Palladini, Vaishali Sanchorawala, Ashutosh Wechalekar, Update On Treatment Of Light Chain Amyloidosis. Haematologica February 2014 99: 209-221

Michael Rosenzweig and Heather LandauLight chain (AL) amyloidosis: update on diagnosis and management. Journal of Hematology & Oncology 2011, 4:47  

Sanchorawala V, Wright DG, Quillen K, Finn KT, Dember LM, Berk JL, et al. Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis. Bone Marrow Transplant. 2007 (b) Sep;40(6):557-562.

Alastair Smith Finn Wisloff Diana Samson on behalf of the UK Myeloma Forum, Nordic Myeloma Study Group and British Committee for Standards in Haematology. (2006) Guidelines on the diagnosis and management of multiple myeloma 2005. British Journal of Haematology 132:4, 410-451

Guidelines on the diagnosis and management of AL amyloidosis.
British Journal of Haematology 125 (6), 681-70, 2004

Sanchorawala V, Wright DG, Quillen K, Finn KT, Dember LM, Berk JL, et al. Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis. Bone Marrow Transplant. 2007 (b) Sep;40(6):557-562.

Sanchorawala V, Skinner M, Quillen K, Finn KT, Doros G, Seldin DC. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation. Blood. 2007 (a) Aug 2;

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