Cyclophosphamide-induced cardiomyopathy as a complication of autological hemapoietic stem cell transplantation in a patient with multiple sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system. Despite significant advances in treatment, MS remains a serious health problem requiring the development of new therapeutic approaches. High-dose immunosuppressive therapy (HIST) and autologous hematopoietic stem cell transplantation (auto-HSCT) is one of the promising methods of treating MS, showing a long-term effect. However, the implementation of HIST-auto-HSCT is accompanied by a risk of cardiotoxicity, which significantly limits its use and requires close attention. This article presents a successfully resolved case of toxic cardiomyopathy, caused by HIST-auto-HSCT in a woman without a history of cardiovascular pathology.

The purpose of the article is to draw attention to the problem of cardiotoxicity of HIST-auto-HSCT in the treatment of MS, to emphasize the need to develop new strategies to reduce this risk and improve the safety of the method. The article will consider the mechanisms of cardiotoxicity caused by the components of HIST, as well as risk factors, clinical manifestations and diagnostic methods of cardiac complications.

1. Iqubal A., Iqubal M. K., Sharma S. et al. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sci. 2019;218:112–131. https://doi.org/10.1016/j.lfs.2018.12.018.

2. Lyon A. R., López-Fernández T., Couch L. S. et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (ICOS). European Heart Journal. 2022;43:4229–4361. https://doi.org/10.1093/eurheartj/ehac244.

3. Snowden J. A., Hill G. R., Hunt P. et al. Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide. Bone Marrow Transplantation. 2000;26:309–313.

4. Buja L. M., Ferrans V. J., Graw R. G., Jr. Cardiac pathologic findings in patients treated with bone marrow transplantation. Hum. Pathol. 1976;7:17–45. https://doi.org/10.1016/S00468177(76)80004-4.

5. Shanholtz C. Acute life-threatening toxicity of cancer treatment. Crit Care Clin. 2001;17:483–502.

6. Morandi P., Ruffini P. A., Benvenuto G. M. et al. Serum cardiac troponin I levels and ECG/echo monitoring in breast cancer patients undergoing high-dose (7 g/m2) cyclophosphamide. Bone Marrow Transplant. 2001;28:277–282.

7. Braverman A. C., Antin J. H., Plappert M. T. et al. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol. 1991;9:1215–1223.

8. Gottdiener J. S., Appelbaum F. R., Ferrans V. J. et al. Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med. 1981;141:758–763.

9. Appelbaum F. R., Strauchen J. A., Graw R. G. et al. Acute lethal carditis caused by high-dose combination chemotherapy. A unique clinical and pathological entity. Lancet. 1976;1:58–62.

10. Katayama M., Imai Y., Hashimoto H. et al. Fulminant fatal cardiotoxicity following cyclophosphamide therapy. J Cardiol. 2009;54:330–334.

11. Kamezaki K., Fukuda T., Makino S., Harada M. Cyclophosphamide-induced cardiomyopathy in a patient with seminoma and a history of mediastinal irradiation. Intern Med. 2005;44:120–123.

12. Goldberg M. A., Antin J. H., Guinan E. C., Rappeport J. M. Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood. 1986;68:1114–1118.

13. Birchall I. W., Lalani Z., Venner P., Hugh J. Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy. Br J Radiol. 2000;73:1112–1114.

14. Nieto Y., Cagnoni P. J., Bearman S. I. et al. Cardiac toxicity following high-dose cyclophosphamide, cisplatin, and BCNU (STAMP-I) for breast cancer. Biol Blood Marrow Transplant. 2000;6:198–203.

15. Nakamae H., Hino M., Akahori M. et al. Predictive value of QT dispersion for acute heart failure after autologous and allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2004;76:1–7.

16. Sharrack B., Saccardi R., Alexander T. et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee ofEBMT and ISCT (JACIE). Bone Marrow Transplantation. 2020;55:283–306.

17. Nieto Y., Cagnoni P. J., Bearman S. I. et al. Cardiac toxicity following high-dose cyclophosphamide, cisplatin, and BCNU (STAMP-I) for breast cancer. Biol Blood Marrow Transplant. 2000;6:198–203.

18. Cardinale D., Sandri M. T., Martinoni A. et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol. 2000;36:517–522.

19. Cardinale D., Sandri M. T., Colombo A. et al. Prognostic value of troponin I in cardiac risk stratifi of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109:2749–2754.

20. Stone J. R., Kanneganti R., Abbasi M., Akhtari M. Monitoring for chemotherapy-related cardiotoxicity in the form of left ventricular systolic dysfunction: A review of current recommendations. JCO Oncol Pract. 2021;17(5):228–236.

21. Dhesi S., Chu M.P., Blevins G. et al. Cyclophosphamide-induced cardiomyopathy: A case report, review, and recommendations for management. J Investig Med High Impact Case Rep. 2013;1(1):2324709613480346. https://doi.org/10.1177/2324709613480346.

22. Medeiros Junior W. L. G., Demore C. C., Mazaro L. P. et al. Urinary tract infection in patients with multiple sclerosis: An overview. Mult Scler Relat Disord. 2020;46:102462.