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Recent Improvements in Survival in Primary Systemic Amyloidosis and the Importance of an Early Mortality Risk Score

      OBJECTIVE

      To examine whether the outcome of patients with primary systemic amyloidosis (AL) has improved over time and to identify predictors of early mortality in patients with AL.

      PATIENTS AND METHODS

      We studied 2 separate cohorts of patients. The first cohort, consisting of 1998 patients with AL seen at Mayo Clinic between January 1977 and August 2006, was used to examine the trends in overall survival (OS) from diagnosis during this 30-year period. The second cohort, consisting of 313 patients seen between September 2006 and August 2009, was used to validate a model for predicting early mortality.

      RESULTS

      The 4-year OS from diagnosis improved during each decade of follow-up: 21%, 24%, and 33%, respectively, for the periods 1977-1986, 1987-1996, and 1997-2006 (P<.001). Within the last group (1997-2006), 4-year OS during 1997-1999, 2000-2002, and 2003-2006 was 28%, 30%, and 42%, respectively (P=.02). However, the 1-year mortality remained high during the 30-year period. A risk stratification score using cardiac troponin T, N-terminal probrain natriuretic peptide, and uric acid identified patients at risk of early mortality. The 1-year mortality with 0, 1, 2, or 3 risk factors was 19%, 37%, 61%, and 80%, respectively, in this training cohort of 459 patients. This was confirmed in a validation cohort of 313 patients.

      CONCLUSION

      Survival in AL has improved over time, with maximum improvement occurring in the past decade. However, early mortality remains high, and prospective identification of patients at risk of early mortality may allow development of risk-adapted strategies.
      AL (primary systemic amyloidosis), CI (confidence interval), cTnT (cardiac troponin T), NT-proBNP (N-terminal pro-brain natriuretic peptide), OS (overall survival), SCT (stem cell transplant)
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      REFERENCES

        • Kyle RA
        • Bayrd ED
        “Primary” systemic amyloidosis and myeloma: discussion of relationship and review of 81 cases.
        Arch Intern Med. 1961; 107: 344-353
        • Kyle RA
        • Gertz MA
        Primary systemic amyloidosis: clinical and laboratory features in 474 cases.
        Semin Hematol. 1995; 32: 45-59
        • Gertz MA
        Diagnosing primary amyloidosis.
        Mayo Clin Proc. 2002; 77: 1278-1279
        • Gertz MA
        • Comenzo R
        • Falk RH
        • et al.
        Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004.
        Am J Hematol. 2005; 79: 319-328
        • Skinner M
        AL amyloidosis: the last 30 years.
        Amyloid. 2000; 7: 13-14
        • 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; 110: 3561-3563
        • Gertz MA
        • Lacy MQ
        • Dispenzieri A
        Myeloablative chemotherapy with stem cell rescue for the treatment of primary systemic amyloidosis: a status report.
        Bone Marrow Transplant. 2000; 25: 465-470
        • Dispenzieri A
        • Kyle RA
        • Lacy MQ
        • et al.
        Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study.
        Blood. 2004; 103: 3960-3963
        • Jaccard A
        • Moreau P
        • Leblond V
        • et al.
        High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis.
        N Engl J Med. 2007; 357: 1083-1093
        • Skinner M
        • Sanchorawala V
        • Seldin DC
        • et al.
        High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study.
        Ann Intern Med. 2004; 140: 85-93
        • Dispenzieri A
        • Lacy MQ
        • Kyle RA
        • et al.
        Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival.
        J Clin Oncol. 2001; 19: 3350-3356
        • Kumar SK
        • Mikhael JR
        • Buadi FK
        • et al.
        Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines.
        Mayo Clin Proc. 2009; 84: 1095-1110
        • Kumar SK
        • Rajkumar SV
        • Dispenzieri A
        • et al.
        Improved survival in multiple myeloma and the impact of novel therapies.
        Blood. 2008; 111: 2516-2520
        • Dispenzieri A
        • Lacy MQ
        • Rajkumar SV
        • et al.
        Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosis.
        Amyloid. 2003; 10: 257-261
        • Seldin DC
        • Choufani EB
        • Dember LM
        • et al.
        Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis.
        Clin Lymphoma. 2003; 3: 241-246
        • Palladini G
        • Perfetti V
        • Obici L
        • et al.
        Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation.
        Blood. 2004; 103: 2936-2938
        • Dispenzieri A
        • Lacy MQ
        • Zeldenrust SR
        • et al.
        The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis.
        Blood. 2007; 109: 465-470
        • Wechalekar AD
        • Goodman HJ
        • Lachmann HJ
        • Offer M
        • Hawkins PN
        • Gillmore JD
        Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis.
        Blood. 2007; 109: 457-464
        • Kumar S
        • Hayman SR
        • Buadi F
        • et al.
        A phase II trial of lenalidomide, cyclophosphamide and dexamethasone (RCD) in patients with light chain amyloidosis [abstract 3853].
        Blood (ASH Annual Meeting Abstracts). 2009; 114: 3853
        • Kastritis E
        • Roussou M
        • Migkou M
        • et al.
        A phase I/II study of lenalidomide (R) with low dose dexamethasone (d) and cyclophosphamide (C) for patients with primary systemic (AL) amyloidosis [abstract 428].
        Blood (ASH Annual Meeting Abstracts). 2009; 114: 428
        • Wechalekar AD
        • Lachmann HJ
        • Offer M
        • Hawkins PN
        • Gillmore JD
        Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease.
        Haematologica. 2008; 93: 295-298
        • Zonder JA
        • Sanchorawala V
        • Snyder RM
        • et al.
        Melphalan and dexamethasone plus bortezomib induces hematologic and organ responses in AL-amyloidosis with tolerable neurotoxicity [abstract 746].
        Blood (ASH Annual Meeting Abstracts). 2009; 114: 746
        • Kastritis E
        • Wechalekar AD
        • Dimopoulos MA
        • et al.
        Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis.
        J Clin Oncol. 2010; 28: 1031-1037
        • Sanchorawala V
        • Wright DG
        • Rosenzweig M
        • et al.
        Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial.
        Blood. 2007; 109: 492-496
        • Kaplan EL
        • Meier P
        Non-parametric estimation from incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Dispenzieri A
        • Gertz MA
        • Kyle RA
        • et al.
        Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.
        J Clin Oncol. 2004; 22: 3751-3757
        • Gertz MA
        • Zeldenrust SR
        Treatment of immunoglobulin light chain amyloidosis.
        Curr Hematol Malig Rep. 2009; 4: 91-98
        • Kyle RA
        • Greipp PR
        Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo.
        Blood. 1978; 52: 818-827
        • Kyle RA
        • Gertz MA
        • Greipp PR
        • et al.
        A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine.
        N Engl J Med. 1997; 336: 1202-1207
        • Kumar S
        • Dispenzieri A
        • Gertz MA
        High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis [letter].
        N Engl J Med. 2008; 358: 91
        • Kastritis E
        • Anagnostopoulos A
        • Roussou M
        • et al.
        Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone.
        Haematologica. 2007; 92: 1351-1358
        • Gertz M
        • Lacy M
        • Dispenzieri A
        • et al.
        Troponin T level as an exclusion criterion for stem cell transplantation in light-chain amyloidosis.
        Leuk Lymphoma. 2008; 49: 36-41
        • Dispenzieri A
        • Gertz MA
        • Kyle RA
        • et al.
        Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation.
        Blood. 2004; 104: 1881-1887
        • Kumar S
        • Dispenzieri A
        • Lacy MQ
        • et al.
        Serum uric acid: novel prognostic factor in primary systemic amyloidosis.
        Mayo Clin Proc. 2008; 83: 297-303
        • Fang J
        • Alderman MH
        Serum uric acid and cardiovascular mortality: the NHANES I epidemiologic follow-up study, 1971-1992.
        JAMA. 2000; 283: 2404-2410
        • Sakai H
        • Tsutamoto T
        • Tsutsui T
        • Tanaka T
        • Ishikawa C
        • Horie M
        Serum level of uric acid, partly secreted from the failing heart, is a prognostic marker in patients with congestive heart failure.
        Circ J. 2006; 70: 1006-1011
        • Hoeper MM
        • Hohlfeld JM
        • Fabel H
        Hyperuricaemia in patients with right or left heart failure.
        Eur Respir J. 1999; 13: 682-685
        • Leyva F
        • Anker S
        • Swan JW
        • et al.
        Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure.
        Eur Heart J. 1997; 18: 858-865