Attainment of Complete Hematological Remission is Crucial for Extended Survival of AL Amyloidosis Patients with Cardiac Involvement

Česká verzia

Authors: T. Pika ¹; P. Lochman ²; J. Vymětal ¹; R. Metelka ¹; J. Minařík ¹; P. Látalová ³; J. Zapletalová ⁴; J. Bačovský ¹; V. Ščudla ¹
Authors place of work: III. interní klinika – nefrologická, revmatologická, endokrinologická LF UP a FN Olomouc ¹; Oddělení klinické biochemie, FN Olomouc ²; Ústav klinické a molekulární patologie LF UP a FN Olomouc ³; Ústav lékařské biofyziky LF UP v Olomouci ⁴
Published in the journal: Klin Onkol 2013; 26(5): 343-347
Category: Original Articles

Summary

Background:
Symptomatic cardiac involvement is the most important prognostic factor in AL amyloidosis patients. Long‑term survival is limited not only by cardiac involvement condition, but also by limited choice of treatment with unsatisfactory results. The aim of the present report is to assess the effect of achieved treatment response on survival of AL amyloidosis patients with symptomatic cardiac involvement under conventional treatment.

Material and Methods:
The monitored patient set consisted of 19 patients with systemic AL amyloidosis and symptomatic cardiac involvement, treated and monitored at the III. Clinic of Internal Medicine between 2004 and 2012. The male : female ratio was 17 : 2, and the age median was 64 (range 48 to 78 years). Thirteen patients died within the monitored period. Functional status was defined according to the NYHA classification, where five patients had class II involvement, 10 patients had class III involvement, and four patients had class IV involvement. Treatment response was assessed by the application of modified IMWG and ISA criteria; all patients were undergoing conventional treatment. Nine patients were treated by a combination of alkylating agents (alkeran, cyclophosphamide), six were treated by a combination treatment with thalidomide, and four were treated by a combination of bortezomib and dexamethasone. Data were analyzed with software SPSS v. 15 (SPSS, Inc., Chicago, USA). Log Rank Test was applied to survival evaluation.

Results:
The statistical analysis included only 13 patients who underwent at least three months of treatment, where six patients attained complete remission (CR), four patients attained partial remission (PR), and three patients attained only stabilization of disease (SD). Significant difference in patient survival was found to be correlated with attained hematological response, where the patients who attained CR had median survival of 39 months vs 10 months in patients who attained PR or SD (p = 0.005).

Conclusion:
The results indicate that attainment of complete hematological remission is associated with significantly longer survival of AL amyloidosis patients with symptomatic cardiac involvement.

Key words:
amyloidosis – cardiomyopathy – treatment – survival

This study was supported by grant NT 12451/5.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
17. 3. 2013

Accepted:
27. 3. 2013

Zdroje

1. Ščudla V, Pika T. Současné možnosti diagnostiky a léčby systémové AL‑ amyloidózy. Vnitř Lék 2009; 55 (Suppl 1): 77– 87.

2. Sipe JD, Benson MD, Buxbaum JN et al. Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committe of International Society of Amyloidosis. Amyloid 2010; 17(3– 4): 101– 104.

3. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med 2003; 349(6): 583– 596.

4. Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol 2011; 29(14): 1924– 1933.

5. Dispenzieri A, Gertz MA, Buadi F. What do I need to know about immunoglobulin light chain (AL) amyloidosis? Blood Rev 2012; 26(4): 137– 154.

6. Kyle RA, Greipp PR, O’Fallon WM. Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases. Blood 1986; 68(1): 220– 224.

7. Bird J, Cavenagh J, Hawkins P et al. Guidelines on the diagnosis and management of AL amyloidosis. Br J Haematol 2004; 125(6): 681– 700.

8. Gertz MA. Immunoglobulin light chain amyloidosis: 2012 update on diagnosis, prognosis, and treatment. Am J Hematol 2012; 87(2): 183– 189.

9. Esplin BL, Gertz MA. Current trends in diagnosis and management of cardiac amyloidosis. Curr Probl Cardiol 2013; 38(2): 53– 96.

10. Kapoor P, Thenappan T, Singh E et al. Cardiac amyloidosis: a practical approach to diagnosis and management. Am J Med 2011; 124(11): 1006– 1015.

11. 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. Am J Hematol 2005; 79(4): 319– 328.

12. Gertz MA, Merlini G. Definition of organ involvement and response to treatment in AL amyloidosis: an updated consensus opinion. Amyloid 2010; 17 (Suppl 1): 48– 49.

13. 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(18): 3751– 3757.

14. Dispenzieri A, Kyle RA, Merlini G et al. International Myeloma Working Group guidelines for serum‑free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23(2): 215– 224.

15. Comenzo RL, Reece D, Palladini G et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light‑chain amyloidosis. Leukemia 2012; 26(11): 2317– 2325.

16. Leung N, Leung TR, Cha SS et al. Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first‑year survival after stem cell transplantation in AL amyloidosis patients. Blood 2005; 106(10): 3353– 3357.

17. Madan S, Kumar SK, Dispenzieri A et al. High‑dose melphalan and peripherial blood stem cell transplantation for light‑chain amyloidosis with cardiac involvement. Blood 2012; 119(5): 1117– 1122.

18. Sanchorawala V, Wright DG, Seldin DC et al. High‑dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial. Bone Marrow Transplant 2004; 33(4): 381– 388.

19. Bird J, Cavenagh J, Hawkins P et al. Guidelines on the diagnosis and management of AL amyloidosis. Brit J Haematol 2004; 125(6): 681– 700.

20. Palladini G, Russo P, Nuvolone M et al. Treatment with oral melphalan plus dexamethasone produces long‑term remissions in AL amyloidosis. Blood 2007; 110(2): 787– 788.

21. Lebovic D, Hoffman J, Levine BM et al. Predictors of survival in patients with systemic light‑chain amyloidosis and cardiac involvement initially ineligible for stem cell transplantation and treated with oral melphalan and dexamethasone. Brit J Haematol 2008; 143(3): 369– 373.

22. Sanchorawala V, Wright DG, Seldin DC et al. Low‑dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis. Brit J Haematol 2002; 117(4): 886– 889.

23. Dietrich S, Schönland SO, Benner A et al. Treatment with intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with newly diagnosed systemic light chain amyloidosis and severe cardiac involvement. Blood 2010; 116(4): 522– 528.

24. Palladini G, Russo P, Lavatelli F et al. Treatment of patients with advanced cardiac amyloidosis with oral melphalan, dexamethasone, and thalidomide. Ann Hematol 2009; 88(4): 347– 350.

25. Kastritis E, Anagnostopoulos A, Roussou M et al. Treatment of light chain (AL) amyloidosis with combination of bortezomib and dexamethasone. Haematologica 2007; 92(10): 1351– 1358.

26. Mikhael JR, Schuster SR, Jimenez‑ Zepeda VH et al. Cyclophosphamide‑ bortezomib‑ dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 2012; 119(9): 4391– 4394.

27. Adam Z, Pour L, Krejčí M et al. Léčba AL‑ amyloidózy – výsledky jednoho pracoviště a přehled publikovaných zkušeností s novými léky (bortezomibem, thalidomidem a lenalidomidem) u AL‑ amyloidózy. Vnitř Lék 2010; 56(3): 190– 209.

28. Venner CP, Lane T, Foard D et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression‑free survival. Blood 2012; 119(19): 4387– 4390.

29. Dubrey SW, Reece DE, Sanchorawala V et al. Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects. QJM 2011; 104(11): 957– 970.

30. Honek T, Krejci J, Spinarova L et al. Heart transplantation for cardiac light chain amyloidosis with subsequent autologous stem cell transplantation. Cor Vasa 2013. Available from: http:/ / dx.doi.org/ 10.1016/ j.crvasa.2012.11.015.