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Heart transplantation and the subsequent treatment of AL amyloidosis


Authors: Z. Adam 1;  J. Krejčí 2;  M. Krejčí 1;  P. Němec 3;  L. Špinarová 2;  V. Žampachová 4;  Z. Čermáková 5;  T. Pika 6;  L. Pour 1;  Z. Kořístek 1,7;  M. Tomíška 1;  P. Szturz 1;  Z. Král 1;  J. Mayer 1
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Mayer, CSc. 1;  Mezinárodní centrum klinického výzkumu – I. interní kardio-angiologická klinika LF MU a FN u sv. Anny Brno, přednostka prof. MUDr. Lenka Špinarová, Ph. D. 2;  Centrum kardiovaskulární a transplantační chirurgie Brno, ředitel doc. MUDr. Petr Němec, CSc. 3;  I. patologicko-anatomický ústav LF MU a FN u sv. Anny Brno, přednostka prof. MUDr. Markéta Hermanová, Ph. D. 4;  Oddělení klinické biochemie FN Brno, KLM LF MU, přednosta doc. MUDr. Milan Dastych, CSc., MBA 5;  III. interní klinika – nefrologie, revmatologie a endokrinologie LF UP a FN Olomouc, přednosta prof. MUDr. Josef Zadražil, CSc. 6;  Integrované centrum celulární a regenerativní medicíny, Mezinárodní centrum klinického výzkumu, FN u sv. Anny Brno 7
Published in: Vnitř Lék 2013; 59(2): 136-147
Category: Case Report

Overview

Severe damage to the heart caused by AL amyloid deposits is a contraindication of high-dose chemotherapy with autologous haematopoietic stem cell transplantation. Severe heart damage caused by AL amyloid results in frequent life-threatening complications, even during the course of the classical chemotherapy treatment and it often makes keeping to the treatment schedule impossible. Scheduling heart transplantation before the treatment of AL amyloidosis will significantly improve the patients’ overall condition and enable them to undergo the intensive AL amyloidosis treatment with the hope that a long-term complete remission may be achieved.

Case descriptions:
Transplantations of heart damaged by AL amyloid deposits were conducted in three patients; two men, age 48 and 54, and one woman, age 63. In the interval of 3–6 months from the heart transplantation before the scheduled AL amyloidosis treatment was initiated, an examination of bone marrow, the concentration of monoclonal immunoglobulin and free light chains was carried out. Both men had more than 10% of plasma cells in the bone marrow after the heart transplantation and the concentrations of the λ free light chains were pathologically increased. During the first-line therapy, autologous haematopoietic stem cells were harvested from peripheral blood after mobilizaton with granulocyte growth factor (filgrastim) at the dose of 5 µg/kg twice a day. During the administration of filgrastim until the end of the haematopoietic stem cell harvest, the combined immunosuppressive treatment was reduced and a corticosteroid dose was compensatory increased. The prophylactic antiviral drug valganciclovir was discontinued during the haematopoietic stem cell harvest. High-dose chemotherapy (melphalan 100 mg/m2) with autologous haematopoietic stem cell transplantation followed. In the interval from administering melphalan until the rise in neutrophil count over 2 x 109/l, antiviral prophylaxis was discontinued again, the immunosuppressive drug doses were reduced and corticoid doses were slightly increased. High-dose chemotherapy with melphalan at the of 100 mg/m2 was tolerated without major complications and without mucositis; however, in neither of the male patients did it lead to a complete haematological remission. Consequently, the second-line therapy followed using bortezomib combined with dexamethasone and also with cyclophosphamide or doxorubicin. One of these two patients reached a complete haematological remission after the bortezomib therapy; the values of free light chains were normal, immunofixation was negative, and clonal plasma cells were absent in the bone marrow. In the case of the other patient, the bortezomib therapy only induced partial remission. In this case, the third-line therapy followed, applying a combination of lenalidomide, dexamethasone and cyclophosphamide. This therapy significantly reduced the values of free light chains; however, their ratio remained pathological. To conclude, the latter response can be described as a very good partial remission. Both men currently show no signs of disease activity and are in a good clinical condition 28 and 30 months after the heart transplantation. The third heart transplantation, due to severe heart damage by AL amyloid deposits, was conducted in a woman aged 63. An examination of this woman three months after the heart transplantation showed that the original pathological values of free light chains became normal. The woman had approx. 8% of clonal plasma cells before the heart transplantation. Three months after the heart transplantation the bone marrow contained only 3% of polyclonal plasma cells. In this case, the immunosuppressive treatment with corticosteroids after the heart transplantation probably induced a complete haematologic remission. The woman is in a complete AL amyloidosis remission seven months after the heart transplantation.

Conclusion:
It was beneficial to perform the heart transplantation first and to initiate the AL amyloidosis treatment no sooner than three months after the heart transplantation in patients with severe heart damage caused by AL amyloid deposits. If the patients are in a good clinical conditions, autologous haematopoietic stem cells can be harvested after the heart transplantation and high-dose chemotherapy can be offered to the patients. If this intensive treatment does not induce remission, it is necessary to apply additional alternative treatments.

Key words:
AL amyloidosis – high-dose chemotherapy – bortezomib – lenalidomide – cardiomyopathy – heart biopsy


Sources

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

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

3. Abraham RS, Geyer SM, Price-Troska L et al. Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome of light chain-associated amyloidosis. Blood 2003; 101: 3801–3808.

4. Comenzo RL, Zhang Y, Martinez C et al. The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig VL germ line use and clonal plasma cell burden. Blood 2001; 98: 714–720.

5. Bellotti V, Chiti F. Amyloidogenesis in its biological environment: challenging a fundamental issue in protein mis-folding diseases. Curr Opin Struct Biol 2008; 18: 771–779.

6. Adam Z, Ščudla V. Klinické projevy a diagnostika AL-amyloidózy a některých dalších typů amyloidóz. Vnitř Lék 2001; 47: 36–45.

7. Tichý M. Primární amyloidóza. Lék Zpr UK Hradec Králové 1999; 44: 99–107.

8. Kroupa R, Dastych M, Šenkyřík M et al. Systémová amyloidóza s dominující klinickou manifestací v trávicím traktu. Vnitř Lék 2005; 51: 588–592.

9. Ryšavá R. Amyloidóza ledvin. Postgrad Med 2006; 8: 207–212.

10. Ryšavá R. Léčba paraproteinemické nefropatie a primární amyloidózy ledvin. Aktual v Nefrol 2005; 11: 62–65.

11. Linhartová K, Daum O. Srdeční amyloidóza. Cor et Vasa, 2005; 47: 328.

12. Kastritis E, Dimopoulos MA. Prognosis and risk assessment in AL amyloidosis – state of the art. Amyloid 2011; 18: (Suppl. 1): 84–86.

13. Mekinian A, Lions C, Leleu X et al. Amyloidosis Study Group. Prognosis assessment of cardiac involvement in systemic AL amyloidosis by magnetic resonance imaging. Am J Med 2010; 123: 864–868.

14. Kristen AV, Giannitsis E, Lehrke S et al. Assessment of disease severity and outcome in pa­tients with systemic light-chain amyloidosis by the high-sensitivity troponin T assay. Blood 2010; 116: 2455–2461.

15. Kumar S, Dispenzieri A, Lacy MQ et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 2012; 30: 989–995.

16. Dispenzieri A, Gertz M, Kyle A et al. Serum cardiac troponins and N-terminal Pro-Brain Netriuretic Peptide: A staging system for primary AL--amyloidosis. J Clin Oncol 2004; 22: 3751–3757.

17. Audard V, Matignon M, Weiss L et al. Successful long-term outcome of the first combined heart and kidney transplant in a patient with systemic Al amyloidosis. Am J Transplant 2009; 9: 236–240.

18. Mignot A, Varnous S, Redonnet M et al. Heart transplantation in systemic (AL) amyloidosis: a retrospective study of eight French pa­tients. Arch Cardiovasc Dis. 2008; 101: 523–532.

19. Lacy MQ, Dispenzieri A, Hayman SR et al. Autologous stem cell transplant after heart transplant for light chain (Al) amyloid cardiomyopathy. J Heart Lung Transplant 2008; 27: 823–829.

20. Mignot A, Bridoux F, Thierry A et al. Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis. Haematologica. 2008; 93: e32–e35.

21. Sack FU, Kristen A, Goldschmidt H et al. Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis. Eur J Cardiothorac Surg 2008; 33: 257–262.

22. Perz JB, Kristen AV, Rahemtulla A et al. Long--term survival in a patient with AL amyloidosis after cardiac transplantation followed by autologous stem cell transplantation. Clin Res Cardiol 2006; 95: 671–674.

23. Gillmore JD, Goodman HJ, Lachmann HJ et al. Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood 2006; 107: 1227–1229.

24. Dubrey SW, Burke MM, Hawkins PN et al. Cardiac transplantation for amyloid heart disease: the United Kingdom experience. J Heart Lung Transplant 2004; 23: 1142–1153.

25. Jedlička F, Elbl L, Vášová I et al. Chronický fatigue syndrome u pacientů s nádorovou chorobou. Vnitř Lék 2007; 53: 979–985.

26. Elbl L, Vášová I, Navrátil M et al. Srovnání plazmatických hladin B-natriuretic peptidu s echokardiografickými indikátory funkce levé komory po léčbě doxorubicinen. Vnitř Lék 2006; 52: 563–570.

27. Elbl L, Vášová I, Krejcí M et al. Efekt vysokodávkované chemoterapie a následující transplantace krvetvorných buněk na funkci levého komory u pacientů s maligními lymfomy léčenými doxorubicinen. Vnitř Lék 2006; 52: 221–231.

28. Elbl L. Poruchy kardiovaskulárního systému v průběhu léčby maligních chorob. Vnitř Lék 2002; 48: 619–625.

29. Elbl L, Vášová I, Kiss I et al. Kardiotoxicita protinádorové léčby. Vnitř Lék 2000; 46: 178–183.

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