Late cardiotoxicity of high-dose chemotherapy according to the modified NHL-BFM-90 program in adult patients with diffuse large B-cell lymphoma


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Abstract

Aim. To evaluate the late cardiotoxicity (CT) of high-dose chemotherapy (CT) according to the modified NHL-BFM-90 (mNHL-BFM-90) protocol in adult patients with diffuse large B-cell lymphoma (DLBCL). Subjects and methods. The results of electrocardiography (ECG) and echocardiography (echoCG) were analyzed in 40 DLBCL patients treated according to the mNHL-BFM-90 program in the Hematology Research Center (HRC), Russian Academy of Medical Sciences (RAMS), in 2002 to 2009. A study group consisted of 20 men and 20 women whose age was 31 to 76 years; median age was 56.5 years at the time of their examination and the median follow-up time after therapy was 6 years. The individual cumulative dose of doxorubicin was 150-300 mg/m2. A comparison group included 19 patients receiving СНОР/R-СНОР CT in HRC, RAMS, in 2002 to 2009. Out of them, there were 8 men and 11 women whose age was 39 to 78 years median age was 70 years at the time of their examination. The individual cumulative dose of doxorubicin was 200—400 mg/m2. ECG and echoCG were carried out before and 5 years or more after CT. Results. Out of the 40 patients with DLBCL, the signs of subclinical cardiomyopathy (CMP) were detected in 24 (60%) patients; no clinical manifestations of congestive heart failure (CHF) were found in any patient. In the comparison group of 19 patients receiving СНОР/R-СНОР CT, 14 (74%) patients were found to have signs of subclinical CMP and no clinical signs of CHF. The summary toxicity index significantly depended on age (p=0.03) and a history of heart disease (p=0.3); it was significantly higher after CHOP/R-CHOP CT (p=0.05). There was a statistically significant relationship of the risk of subclinical CMP to the history of heart diseases (p=0.05). Conclusion. Late cardiotoxicity of the mNHL-BFM-90 program does not exceed the toxicity of standard CHOP/R-CHOP therapy. Post-CT Echo-CG and ECG findings showed that the patients with the most marked subclinical signs of CMP in both groups had cardiotoxicity risk factors, such as coronary heart disease, hypertensive disease, or diabetes in their history. No clinically significant CHF was identified in any patient.

References

  1. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019-5032.
  2. Воробьев А.И. Руководство по гематологии. Т. 2. М.: Ньюдиамед; 2003:55, 98-100.
  3. Jerkeman M, Anderson H, Cavallin-Ståhl E, Dictor M, Hagberg H, Johnson A, Kaasa S, Kvaløy S, Sundström C, Akerman M. CHOP versus MACOP-B in aggressive lymphoma — a Nordic Lymphoma Group randomized trial. Ann Oncol. 1999;10(9):1079-1086.
  4. Hasselblom S, Ridell B, Nilsson-Ehle H, Andersson PO. The impact of gender, age and patient selection on prognosis and outcome in diffuse large B-cell lymphoma — a population-based study. Leuk Lymphoma. 2007;48(4):736-745.
  5. Horning S, Weller E, Kim KM, Earle JD, O’Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkins lymphoma: Eastern Cooperative Oncology Group Study 1484. J ClinOncol. 2004;22(15):3032-3038.
  6. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. New Engl J Med. 1993;328:1002-1006.
  7. Магомедова А.У., Кравченко С.К., Кременецкая А.М., Звонков Е.А., Барях Е.А., Мангасарова Я.К., Воробьев А.И. Девятилетний опыт лечения больных диффузной В-крупно­клеточной лимфосаркомой. Терапевтический архив. 2011;7:5-10.
  8. Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040-2045.
  9. Michael Pfreundschuh, Evelyn Kuhnt. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diff use large-B-cell lymphoma: 6-year results of an open-label randomized study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12:1013-1022.
  10. Zvonkov E. Six-year experience in the treatment of primary aggressive gastric lymphomas with modified NHL-BFM-90 protocol. Haematologica. 2010;95:632-632.
  11. Звонков Е.Е., Кременецкая А.М., Кравченко С.К., Махиня В.А., Капланская И.Б., Обухова Т.Н., Воробьев И.А. Эффективность консервативной терапии лимфосаркомы желудка. Терапевтический архив. 2008;7:18-26.
  12. Кравченко С.К., Магомедова А.У., Замятина В.А., Марголин О.В. Высокодозная терапия генерализованной формы (без вовлечения костного мозга) диффузной В-крупно­клеточной лимфосаркомы у больных старшего возраста. Гематология итрансфузиология. 2008;53(3):6-9.
  13. Jones RL, Ewer MS. Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs. Expert Rev Antican Ther. 2006;6(9):1249-1269.
  14. Schimmel KJ, Richel DJ, van den Brink RB, Guchealaar HJ. Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev. 2004;30(2): 181-191.
  15. Yeh ET. Cardiotoxicity induced by chemotherapy and antibody therapy. Ann Rev Med. 2006;57:485-498.
  16. Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, Durand JB, Gibbs H, Zafarmand AA, Ewer MS. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109(25):3122-3131.
  17. Myers C. Role of iron in anthracycline action. In: Hacker M, Lazo J, Tritton T, eds. Organ Directed Toxicities of Anticancer Drugs. Boston, Mass: Martinus Nijhoff; 1988:17-30.
  18. Lewis W, Kleinerman J, Puszkin S. Interaction of Adriamycin in vitro with cardiac myofibril proteins. Canc Res. 1982;50:547-553.
  19. Chaiswing L, Cole MP, St Clair DK, Ittarat W, Szweda LI, Oberley TD. Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury. Toxicol Pathol. 2004;32(5):536-547.
  20. Kupari M, Volin L, Suokas A, Timonen T, Hekali P, Ruutu T. Cardiac involvement in bone marrow transplantation: electrocardiographic changes, arrhythmias, heart failure and autopsy findings. Bone Marrow Transplant. 1990;5:91-98.
  21. Quezado ZM, Wilson WH, Cunnion RE, Parker MM, Reda D, Bryant G, Ognibene FP. High-dose ifosfamide is associated with severe, reversible cardiac dysfunction. Ann Intern Med. 1993;118:31-36.
  22. Yancey RS, Talpaz M. Vindesine-associated angina and ECG changes. Cancer Treat Rep. 1982;66:587-589.
  23. Airey CL, Dodwell DJ, Joffe JK, Jones WG. Etoposide-related myocardial infarction. Clin Oncol. 1995;7:135.
  24. Chaladze T, Megreladze I, Zodelava M. Early cardiotoxicity induced by treatment of hematologic malignancies and the riskfactors of its manifestation. Georgian Med News. 2005;129:117-119.
  25. Pai VB, Nahata MC. Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. 2000;22(4):263-302.
  26. Benjamin R. The schedule dependency of the cardiotoxicity of adriamycin: its relevance to pharmacokinetic parameters. In: Muggia F, ed. Cancer Treatment and the Heart. Baltimore, Md: The Johns Hopkins University Press; 1992:278.
  27. Lipshultz SE, Lipsitz SR, Sallan SE, Dalton VM, Mone SM, Gelber RD, Colan SD. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol. 2005;23(12):2629-2636.
  28. Lipshultz SE. Exposure to anthracyclines during childhood causes cardiac injury. Semin Oncol. 2006;33(3):8-14.
  29. Elbl L, Chaloupka V, Vásová I, Kiss I, Jancík J, Vorlícek J, Navrátil M. Changes in left ventricular function during chemotherapy with doxorubicin. Vnitr Lek. 1999;45(7):395-402.
  30. Hequet O, Le QH, Moullet I, Pauli E, Salles G, Espinouse D, Dumontet C, Thieblemont C, Arnaud P, Antal D, Bouafia F, Coiffier B. Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults. J Clin Oncol. 2004;22(10):1864-1871.
  31. Moser EC, Noordijk EM, van Leeuwen FE, le Cessie S, Baars JW, Thomas J, Carde P, Meerwaldt JH, van Glabbeke M, Kluin-Nelemans HC. Long-term risk of cardiovascular disease after treatment for aggressive non-Hodgkin lymphoma. Blood. 2006;107:2912-2919.
  32. Hershman DL, McBride RB, Eisenberger A, Tsai WY, Grann VR, Jacobson JS. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin’s lymphoma. JClin Oncol. 2008;26:3159-3165.
  33. Мареев В.Ю., Агеев Ф.Т., Арутюнов Г.П., Коротеев А.В., Ревишвили А.Ш., Беленков Ю.Н., Поздняков Ю.А. Национальные рекомендации ВНОК и ОССН по диагностике и лечению ХСН (третий пересмотр). Сердечная недостаточность. 2010;11(1):1-62.
  34. Grenier MA, Lipshultz SE. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin Oncol. 1998;25(4):Suppl. 10:72-85.
  35. Jensen BV, Skovsgaard T, Nielsen SL. Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol. 2002; 13:5:699-709.
  36. Jensen BV. Cardiotoxic consequences of anthracyclinecontaining therapy in patients with breast cancer. Semin Oncol. 2006;33(3):Suppl. 8:15-21.
  37. Chaladze T, Megreladze I, Zodelava M. Early cardiotoxicity induced by treatment of hematologic malignancies and the riskfactors of its manifestation. Georgian Med News. 2005;129:117-119.
  38. Aggarwal S, Pettersen MD, Bhambhani K, Gurczynski J, Thomas R, L’Ecuyer T. B-type natriuretic peptide as a marker for cardiac dysfunction in anthracyclinetreated children. Pediatr Blood Cancer. 2006;43:12.

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