Cardiac toxicity of high-dose cyclophosphamide in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation.

Abstract

High-dose cyclophosphamide is a well-known mobilization regimen in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Highly differing rates of cardiac complications associated with high-dose cyclophosphamide have been reported. To date, no systematic clinical study has investigated high-dose cyclophosphamide mobilization regimens in multiple myeloma patients and evaluated its cardiotoxicity. We administered high-dose cyclophosphamide (4 g/m2) to 23 consecutive multiple myeloma patients and followed the patients for 15 days by serially measuring the cardiotoxicity biomarkers troponin I (TnI), brain natriuretic peptide (BNP), and endothelin 1 (ET-1). Systolic and diastolic left ventricular function was assessed by complete echocardiography before and at 6 to 8 weeks after the therapy. Patients younger than 55 years showed significant differences between basal TnI levels and TnI concentrations determined at 15 days after high-dose cyclophosphamide treatment (P = .028). Significant differences between basal BNP concentrations and BNP levels measured at 8 hours after high-dose cyclophosphamide treatment were found in the entire group of patients as well as in 2 subgroups, patients younger than 55 years and those older than 55 years (P <.0001, P <.001, and P = .001, respectively). ET-1 results for the entire group of patients showed a significant difference between baseline ET-1 values and ET-1 values determined 8 hours after high-dose cyclophosphamide administration (P = .004). Echocardiographic measurements revealed a barely nonsignificant decrease in cardiac output after high-dose cyclophosphamide infusion compared with pretreatment values (P = .06), a result in accord with echocardiographically detected increases in mild functional mitral regurgitation (P = .025). TnI levels at 15 days after the completion of treatment correlated with left ventricular diastolic dysfunction, as indicated by the s/d index (r = 0.61; P = .04). In conclusion, the significant neurohumoral activation of heart failure occurring after high-dose cyclophosphamide treatment is manifested by an increase in BNP and ET-1 levels, yet without concomitant cardiomyocyte necrosis. BNP levels and to a lesser extent ET-1 levels are much more sensitive indicators of myocardial injury than functional tests, such as echocardiography, whereas diastolic functional parameters are more sensitive predictors of early cyclophosphamide-induced cardiotoxicity. Mild functional mitral regurgitation may develop in patients given high-dose cyclophosphamide therapy.

• Authors: Samo Zver, Vesna Zadnik, Matjaz Bunc, Polona Rogel, Peter Cernelc, Mirta Kozelj
• Journal: International journal of hematology (Int J Hematol) Vol. 85 Issue 5 Pg. 408-14 (Jun 2007) ISSN: 0925-5710 [Print] Japan
• PMID: 17562616 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Biomarkers
• Endothelin-1
• Immunosuppressive Agents
• Troponin I
• Natriuretic Peptide, Brain
• Cyclophosphamide

Topics

• Adult
• Aged
• Biomarkers (blood)
• Cyclophosphamide (administration & dosage, adverse effects)
• Diastole
• Echocardiography
• Endothelin-1 (blood)
• Female
• Graft Rejection (drug therapy)
• Heart Failure (chemically induced, diagnostic imaging, pathology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Male
• Middle Aged
• Multiple Myeloma (therapy)
• Natriuretic Peptide, Brain (blood)
• Transplantation, Autologous
• Troponin I (blood)