Современные методы лечения AL амилоидоза: обзор литературы и собственные данные

А.Г. Смирнова1, С.Н. Бондаренко1, А.А. Кисина2, А.В. Смирнов2, А. Цандер3, Б.В. Афанасьев1

1 Институт детской гематологии, онкологии и трансплантологии им. Р.М. Горбачевой СПбГМУ им. акад. И.П. Павлова, Санкт-Петербург, Российская Федерация

2 Научно-исследовательский институт нефрологии СПбГМУ им. акад. И.П. Павлова, Санкт-Петербург, Российская Федерация

3 Центр трансплантации костного мозга Медицинского университета Гамбург-Эппендорф, Гамбург, Германия


РЕФЕРАТ

AL амилоидоз — достаточно редкое заболевание из группы плазмоклеточных дискразий, имеющее крайне неоднородную клиническую картину и плохой прогноз. В статье представлено краткое описание данной патологии, проведен обзор современных методов лечения, представлены собственные результаты терапии. В исследование включено 46 больных с диагнозом AL амилоидоза, которые получали лечение как с использованием аутологичной трансплантации гемопоэтических стволовых клеток, так и стандартной химиотерапии, включающей комбинацию мелфалана с дексаметазоном и бортезомиба с дексаметазоном.


Ключевые слова: AL амилоидоз, лечение, трансплантация гемопоэтических стволовых клеток, мелфалан, бортезомиб.

Читать статью в PDF pdficon

ЛИТЕРАТУРА 

  1. Falk R.H., Comenzo R.L., Skinner M. The systemic amyloidoses. N. Engl. J. Med. 1997; 337: 898–909.
  2. Kyle R.A., Gertz M.A. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin. Hematol. 1995; 32: 45–59.
  3. Dispenzieri A., Gertz M.A., Kyle R.A. 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: 1881–7.
  4. Dispenzieri A., Gertz M.A., Kyle R.A. et al. Serum cardiac troponins and N-terminal pro-brain natriureticpeptide: a staging system for primary systemic amyloidosis. J. Clin. Oncol. 2004; 22: 3751–7.
  5. Palladini G., Merlini G. Transplantation vs. conventional-dose therapy for amyloidosis. Curr. Opt. Oncol. 2011; 23: 214–20.
  6. Palladini G., Lavatelli F., Russo P. et al. Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 2006; 107: 3854–8.
  7. Bochtler T., Hegenbart U., Heiss C. et al. Evaluation of the serum-free light chain test in untreated patients with AL amyloidosis. Haematologica 2008; 93: 459–62.
  8. Dispenzieri A., Lacy M.Q., Katzmann J.A. et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006; 107: 3378–83.
  9. Kumar S., Dispenzieri A., Katzmann J.A. et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood 2010; 116(24): 5126–9.
  10. Lachmann H.J., Gallimore R., Gillmore J.D. et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br. J. Haematol. 2003; 122: 78–84.
  11. Gertz M.A. Definition of organ involvement and response to treatment in AL amyloidosis: An updated consensus opinion. Amyloid 2010; 17(Suppl. 1): 48–49, abstr. CP-B.
  12. Leung N., Dispenzieri A., Lacy M.Q. et al. Severity of Baseline Proteinuria Predicts Renal Response in Immunoglobulin Light Chain–Associated Amyloidosis after Autologous Stem Cell Transplantation. Clin. J. Am. Soc. Nephrol. 2007; 2: 440–4.
  13. Kyle R.A., Gertz M.A., Greipp Ph.R. et al. Long-term survival (10 years or more) in 30 patients with AL amyloidosis. Blood 1999; 93: 1062–6.
  14. Kyle R.A., Greipp, P.R. Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo. Blood 1978; 52: 818–27.
  15. Kyle R.A., Greipp, P.R., O’Fallon M. Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases. Blood 1986; 68: 220–4.
  16. Kyle R.A., Gertz M.A., Greipp P.R. et al. A trial of three regimen for primary amyloidosis: colchicine alone, melphalan and prednisolone, and melphalan, prednisolone, and colchicine. N. Engl. J. Med. 1997; 336: 1202–7.
  17. Skinner M., Anderson J., Simms R. et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am. J. Med. 1996; 100: 290–8.
  18. Dhodapkar M.V., Hussein M.A., Rasmussen E. et al. Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628. Blood 2004; 104: 3520–6.
  19. Palladini G., Perfetti V., Obici L. et al. Association of melphalan and highdose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood 2004; 103: 2936–8.
  20. Dispenzieri A., Lacy M.Q., Rajkumar S.V. et al. Poor tolerance of thalidomide in patients with primary systemic amyloidosis. Amyloid 2003; 10: 257–61.
  21. Palladini G., Perfetti V., Perlini S. et al. The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood 2005; 105: 2949–51.
  22. Wechalekar А., Goodman H.J.B., Lachmann H.J. et al. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood 2007; 109: 457–64.
  23. Dispenzieri A., Lacy M.Q., Zeldenrust S.R. et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 2007; 109: 465–70.
  24. Sanchorawala V., Wright D.G., Rosenzweig M. et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 2007; 109: 492–6.
  25. Dispenzieri A., Gertz M.A., Hayman S.R. et al. Pomalidomide and dexamethasone for previously treated AL: a phase 2 study. Amyloid J. Protein Folding Dis. 2010; 17: 87.
  26. Dispenzieri A., Buadi F., Laumann K. et al. The activity of pomalidomide in patients with immunoglobulin light chain amyloidosis. Blood 2012; 119: 5397–404.
  27. Wechalekar A., Lachmann H.J., Offer M. et al. Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica 2008; 93(2): 295–8.
  28. Kastritis E., Anagnostopoulos A., Roussou M. et al. Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica 2007; 92: 1351–8.
  29. Zonder J.A., Sanchorawala V., Snyder R.M. et al. Melphalan and Dexamethasone Plus Bortezomib Induces Hematologic and Organ Responses in AL-Amyloidosis with Tolerable Neurotoxicity. Blood 2009; 114: 310–1.
  30. Zonder J., Sanchorawala V., Snyder R. et al. Rapid haematologic and organ responses in patients with AL amyloid treated with bortezomib plus melphalan and dexamethasone. Amyloid J. Protein Folding Dis. 2010; 17: 86–7.
  31. Mikhael J.R., Schuster S.R., Jimenez-Zepeda V.H. et al. The Combination of Cyclophosphamide-Bortezomib-Dexamethasone (CYBOR-D) Is a Highly Effective and Well Tolerated Regimen that Produces Rapid and Complete Hematological Response In Patients with AL Amyloidosis. ASH Annual Meeting Abstracts 2010; 116: 3063.
  32. Comenzo R.L., Vosburgh E., Simms R.W. et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: One-year follow-up in five patients. Blood 1996; 88: 2801–6.
  33. Comenzo R.L., Vosburgh E., Falk R.H. et al. Dose intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. Blood 1998; 91: 3662–70.
  34. Moreau P., Leblond V., Bourquelot P. et al. Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients. Br. J. Haematol. 1998; 101: 766–9.
  35. Gillmore J.D. High-dose melphalan and stem cell rescue for AL amyloidosis. In: Amyloid and Amyloidosis. Ed. by R.A. Kyle, M.A. Gertz). Pearl River: Parthenon Publishing, 1999: 102–4.
  36. Gertz M.A., Lacy M.Q., Gastineau D.A. et al. Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL). Bone Marrow Transplant. 2000; 26: 963–9.
  37. Sanchorawala V. An overview of the use of high dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant. 2001; 28: 637–42.
  38. Skinner M., Sanchorawala V., Seldin D.C. 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.
  39. Dispenzieri A., Kyle R.A., Lacy M.Q. et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood 2004; 103: 3960–3.
  40. Schonland S.O. Current status of hematopoietic cell transplantation in the treatment of systemic amyloid light-chain amyloidosis. Bone Marrow Transplant. 2011 Jul 25: 1–11.
  41. Gertz M.A., Lacy M.Q., Dispenzieri A. et al. Stem cell transplantation for the management of primary systemic amyloidosis. Am. J. Med. 2002; 113: 549–55.
  42. Comenzo R.L., Gertz M.A. Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99: 4276–82.
  43. Cibeira M.T., Sanchorawala V., Seldin D.C. et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood 2011; 118(16): 4346–52.
  44. Sanchorawala V., Wright D.G., Quillen K. et al. Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis. Bone Marrow Transplant. 2007; 40: 557–62.
  45. Quillen K., Seldin D.C., Finn K.T., Sanchorawala V. A second course of high-dose melphalan and auto-SCT for the treatment of relapsed AL amyloidosis. Bone Marrow Transplant. 2011; 46: 976–80.
  46. Cohen A.D., Zhou P., Reich L. et al. Adjuvant dexamethasone (D) ± thalidomide (T) improves hematologic and organ responses after risk-adapted high-dose melphalan with autologous stem cell transplant (SCT) for patients with systemic AL amyloidosis (AL) [abstract]. Blood 2005; 106: 340a, abstr. 1163.
  47. Landau H., Hassoun H., Rosenzweig M.A. et al. Maintained Hematologic and Organ Responses at Two Years Following Stem Cell Transplant In Systemic Light-Chain Amyloidosis (AL) Using Short-Course Bortezomib and Dexamethasone Consolidation Therapy. ASH Annual Meeting Abstracts 2010; 116: 2391.
  48. Sanchorawala V., Wright D.G., Seldin D.C. 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: 381–8.
  49. Perz J.B., Schonland S.O., Hundemer M. et al. High-dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study. Br. J. Haematol. 2004; 127: 543–51.
  50. Schonland S.O., Lokhorst H., Buzyn A. et al. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation. Blood 2006; 107: 2578–84.
  51. Lewis W.D., Skinner M., Simms R.W. et al. Orthotopic liver transplantation for familial amyloidotic polyneuropathy. Clin. Transplant. 1994; 8: 107–10.
  52. Holmgren G., Ericzon B.G., Groth C.G. et al. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet 1993; 341: 1113–6.
  53. Gillmore J.D., Goodman H.J., Lachmann H.J. et al. Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood 2006; 107: 1227–9.
  54. Isoniemi H., Kyllonen L., Ahonen J. et al. Improved outcome of renal transplantation in amyloidosis. Transpl. Int. 1994; 7(Suppl. 1): S298–300.
  55. Hrncic R., Wall J., Wolfenbarger D.A. et al. Antibody-mediated resolution of light chain-associated amyloid deposits. Am. J. Pathol. 2000; 157: 1239–46.
  56. Zhou P., Comenzo R.L. CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy. Blood 2008; 111: 3403–6.
  57. Palladini G. Dispenzieri A., Gertz M.A. et al. Validation of the criteria of response to treatment in AL amyloidosis. Blood 2010; 116: 1364a.