Cardiac damage in autologous bone marrow transplant patients: an autopsy study. Cardiotoxic pretreatment as a major risk factor.

The myocardium was studied histologically at autopsy in seven patients who died 9-85 days (median 22 days) after autologous bone marrow or blood-derived stem-cell transplantation. Clinical investigations including echocardiography suggested normal cardiac function in all patients prior to transplantation. Myeloablation was performed by total body irradiation (1200-1560 cGy) and cyclophosphamide (200 mg/kg). Morphological findings were graded semi-quantitatively and correlated with previous and current therapy. Histological alterations did not correspond to the dosages of myeloablative therapy. However, cardiac failure, the primary cause of death in four patients, was associated with coagulative fiber necroses and contraction band necroses, which may be related to acute cyclophosphamide toxicity. In three of these patients high-dose cardiotoxic pretreatment with anthracyclines and mitoxantrone has been performed beyond the critical cardiotoxic level. High-dose pretreatment was correlated with histological hallmarks of anthracycline heart disease: marked chromatin clumping of myocardial cell nuclei (3/3 patients), occurrence of plurivesicular "adria" cells (3/3 patients), and diffuse interstitial myocardial fibrosis (2/3 patients). Our morphological observations indicate for the first time that pretreatment with anthracyclines and mitoxantrone may enhance cardiotoxicity of myeloablative therapy in bone marrow transplantation.