Bone Marrow Transplantation (2000) 26, 309–313  2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide JA Snowden 1 , GR Hill 1 , P Hunt 2 , S Carnoutsos 1 , RL Spearing 1 , E Espiner 2 and DNJ Hart 1 1 South Island Bone Marrow Transplant Unit and 2 Department of Endocrinology, Christchurch Hospital, Christchurch, New Zealand Summary: Cardiac failure is a known complication of haemopo- ietic stem cell transplantation (HSCT) and is often difficult to diagnose as patients may have multiple medical problems. Since brain natriuretic peptide (BNP) is largely a hormone of cardiac ventricular origin and is released early in the course of ventricu- lar dysfunction, we have examined the value of serial plasma BNP levels for detecting cardiac failure in patients undergoing cytotoxic conditioning for HSCT. Fifteen patients undergoing HSCT were evaluated (10 undergoing autologous HSCT; five undergoing allogeneic HSCT). BNP was measured by radioimmunoassay prior to therapy and weekly for 5 weeks. Seven patients had a significant rise in BNP level (above a previously established threshold of 43 pmol/l associated with cardiac failure), occurring 1–4 weeks post commencement of conditioning. In three of these patients, cardiac failure was sub- sequently diagnosed clinically 3, 9 and 23 days after a BNP level of 43 pmol/l had been detected. These three patients had the highest peak BNP levels for the group and in each case elevation in BNP level occurred for a period exceeding 1 week. Although numbers were relatively small, a BNP 43 pmol/l was significantly associated with the inclusion of high-dose cyclophosphamide in the preparative regi- men (P = 0.02). BNP levels showed no relationship to febrile episodes. In conclusion, these results show that plasma BNP may be used as a marker for early detection of cardiac dysfunction in patients undergo- ing HSCT, particularly if levels are increased for per- iods exceeding 1 week. Measurement of BNP during HSCT may be helpful in patients at risk of cardiac failure, in complex clinical situations and in monitor- ing the cardiotoxicity of preparative regimens. Bone Marrow Transplantation (2000) 26, 309–313. Keywords: bone marrow transplantation; stem cell transplantation; brain natriuretic peptide; cardiac failure The procedure of haemopoietic stem cell transplantation (HSCT) may injure the heart by a number of mechanisms. 1–3 Correspondence: Prof DNJ Hart, Mater Medical Research Institute, Ray- mond Terrace, South Brisbane, Australia Received and accepted 26 April 2000 Conditioning may incorporate cardiotoxic drugs, notably cyclophosphamide. 4,5 Sepsis is also common after HSCT and may produce focal and diffuse myocardial injury. 6 Pre- vious exposure to cardiotoxic drugs, notably anthracyclines, and transfusional iron overload may predispose patients to cardiac dysfunction. Heart failure may be precipitated by the use of hyperhydration regimens, transfused blood components, sodium retaining drugs and impaired renal function. The incidence of clinically significant cardiotoxic- ity has been estimated at between 5 and 10% of patients undergoing autologous or allogeneic HSCT. 7 Early diagnosis of cardiac failure in patients undergo- ing HSCT may be difficult, especially in complex clinical situations where several pathologies often co-exist. For example, clinical and radiological signs may be obscured by lung infiltrates related to infection or graft-versus-host disease (GVHD); oedema and ascites are often due to other causes such as hypoalbuminaemia, veno-occlusive disease and capillary leak syndrome. Echocardiography is often helpful in such situations although it requires an experienced operator and may not be readily available in the acute situation. Cardiac catheterisation, the gold standard in the diagnosis of cardiac failure, is largely impractical due to its invasive nature and the attendant risk of bleeding or infection. Diagnosis of cardiac tox- icity may be more relevant now that HSCT is being used for non-malignant diseases such as haemoglobinopathies, inborn errors of metabolism and autoimmune diseases which may in themselves be associated with underlying cardiac damage. Brain natriuretic peptide (BNP) was originally disco- vered in the porcine brain 8 but was subsequently found to be predominantly a cardiac hormone. 9 Unlike atrial natriuretic peptide (ANP), which is secreted by the atria in response to increased atrial pressure 10 BNP is derived chiefly from the cardiac ventricles in response to ven- tricular stresses. 11 The plasma levels of both peptides are inversely correlated with measures of cardiac function 9 and recent work has shown BNP to be a more sensitive marker of cardiac impairment than ANP. 12,13 Indeed, plasma BNP levels are useful in differentiating acute heart failure from pulmonary disease 14 and for the early diagnosis of heart failure. 15 The aims of this study were to investigate plasma BNP as a marker of ventricular dys- function in patients receiving high-dose preparative regi- mens and HSCT.