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Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin’s lymphoma

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Background The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin’s lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Methods Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. Results There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m2 on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P < 0.001). However, the decrease in diastolic function was similar in both arms (P > 0.05). Conventional Doppler echocardiography yielded consistent findings. Conclusion Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

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  1. Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90:2188–95.

    PubMed  CAS  Google Scholar 

  2. Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998;92:1927–32.

    PubMed  CAS  Google Scholar 

  3. McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–33.

    PubMed  CAS  Google Scholar 

  4. Foran JM, Rohatiner AS, Cunningham D, Popescu RA, Solal-Celigny P, Ghielmini M, et al. European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol. 2000;18:317–24.

    PubMed  CAS  Google Scholar 

  5. Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, et al. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2001;19:389–97.

    PubMed  CAS  Google Scholar 

  6. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  PubMed  CAS  Google Scholar 

  7. Keefe DL. Anthracycline-induced cardiomyopathy. Semin Oncol. 2001;28(4 Suppl 12):2–7.

    PubMed  CAS  Google Scholar 

  8. Shan K, Lincoff AM, Young JB. Anthracycline-induced cardiotoxicity. Ann Intern Med. 1996;125:47–58.

    PubMed  CAS  Google Scholar 

  9. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710–7.

    Google Scholar 

  10. Garypidou V, Perifanis V, Tziomalos K, Theodoridou S. Cardiac toxicity during rituximab administration. Leuk Lymphoma. 2004;45(1):203–4.

    Article  PubMed  CAS  Google Scholar 

  11. Kilickap S, Barista I, Akgul E, Aytemir K, Aksoyek S, Aksoy S, et al. cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol. 2005;16(5):798–804.

    Article  PubMed  CAS  Google Scholar 

  12. Lenaz L, Page JA. Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev. 1976;3:111–20.

    Article  PubMed  CAS  Google Scholar 

  13. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973;32:302–14.

    Article  PubMed  CAS  Google Scholar 

  14. Ali MK, Soto A, Maroongroge D, Bekheit-Saad S, Buzdar AU, Blumenschein GR, et al. Electrocardiographic changes after adriamycin chemotherapy. Cancer. 1979;43:465–71.

    Article  CAS  Google Scholar 

  15. Steinberg JS, Cohen AJ, Wasserman AG, Cohen P, Ross AM. Acute arrhythmogenicity of doxorubicin administration. Cancer. 1987;60:1213–8.

    Article  PubMed  CAS  Google Scholar 

  16. Kilickap S, Akgul E, Aksoy S, Aytemir K, Barista I. Doxorubicin-induced second degree and complete atrioventricular block. Europace. 2005;7(3):227–30.

    Article  PubMed  Google Scholar 

  17. Kilickap S, Barista I, Akgul E, Aytemir K, Aksoy S, Tekuzman G. Early and late arrhythmogenic effects of doxorubicin. South Med J. 2007;100(3):262–5.

    PubMed  Google Scholar 

  18. Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimaeric anti CD-20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999;17:268–76.

    PubMed  CAS  Google Scholar 

  19. Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004;22:4659–64.

    Article  Google Scholar 

  20. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23(18):4117–26.

    Article  PubMed  CAS  Google Scholar 

  21. Lim LC, Koh LP, Tan P. Fatal cytokine release syndrome with chimeric anti-CD20 monoclonal antibody rituximab in a 71-year-old patient with chronic lymphocytic leukemia. J Clin Oncol. 1999;17:1962–3.

    PubMed  CAS  Google Scholar 

  22. Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999;94:2217–24.

    PubMed  CAS  Google Scholar 

  23. Byrd JC, Waselenko JK, Maneatis TJ, Murphy T, Ward FT, Monahan BP, et al. Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusionrelated side effects and rapid blood tumor clearance. J Clin Oncol. 1999;17:791–5.

    PubMed  CAS  Google Scholar 

  24. Hernández JA, Diloy R, Salat D, del Río N, Martínez X, Castellví JM. Fulminant hepatitis subsequent to reactivation of precore mutant hepatitis B virus in a patient with lymphoma treated with chemotherapy and rituximab. Haematologica. 2003;88:22.

    Google Scholar 

  25. Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, et al. Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood. 2003;102:1930.

    Article  PubMed  CAS  Google Scholar 

  26. Cheson BD, Frame JN, Vena D, Quashu N, Sorensen JM. Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphatic leukaemia. J Clin Oncol. 1998;16:2313–20.

    PubMed  CAS  Google Scholar 

  27. Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with high-grade non-Hodgkin’s lymphoma. Am J Med. 1993;94:133–9.

    Article  PubMed  CAS  Google Scholar 

  28. Lenz G, Dreyling M, Hoster E, Wörmann B, Dührsen U, Metzner B, et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005;23(9):1984–92.

    Article  PubMed  CAS  Google Scholar 

  29. Gellrich S, Muche JM, Wilks A, Jasch KC, Voit C, Fischer T, et al. Systemic eight-cycle anti-CD20 monoclonal antibody (rituximab) therapy in primary cutaneous B-cell lymphomas—an applicational observation. Br J Dermatol. 2005;153(1):167–73.

    Article  PubMed  CAS  Google Scholar 

  30. Kimby E. Tolerability and safety of rituximab (MabThera). Cancer Treat Rev. 2005;31(6):456–73.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Saadettin Kilickap.

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Kilickap, S., Yavuz, B., Aksoy, S. et al. Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin’s lymphoma. Med Oncol 25, 437–442 (2008).

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