Cardiac pathologic findings in patients treated with bone marrow transplantation

Cardiac pathologic findings were analyzed in 22 necropsy cases from a series of 29 patients with leukemia, aplastic anemia, or metastatic cancer who had been treated with ablative therapy followed by bone marrow transplantation. Some cardiac alterations were similar to those that occur in patients with hematologic and neoplastic diseases not treated with bone marrow transplantation, and consisted of cardiomegaly, cardiac atrophy, hemorrhage, foci of necrosis due to shock associated with sepsis or hepatic failure, myocardial abscesses secondary to systemic candidiasis or staphylococcal infection, fibrinous pericarditis, and hemosiderosis. Other cardiac alterations were more specifically related to factors associated with transplantation procedure. Six patients exhibited a distinctive interstitial reactive change characterized by the presence of (1) moderate to large numbers of Anitschkow cells, occurring alone or in small cellular aggregates and histiocytes, histiocytic cells with nuclei of the Anitschkow type, lymphoid cells, and plasma cells, and (2) nuclei of the Anitschkow type in cardiac vascular and endocardial smooth muscle, endothelial and Schwann cells, and occasional cardiac muscle cells. This alteration may have been induced by abnormal immune mechanisms, as suggested by the observation that five of the six patients with interstitial change had clinical evidence of graft-versus-host disease. Two patients developed fatal congestive cardiac failure in the early post-transplant period and exhibited myocardial damage with histologic and post-transplant period features indicative of severe acute injury. Findings in these two patients consisted of necrotic muscle cells, which exhibited multiple contraction bands, diastase-resistant PAS staining, and intracellular fibrin deposits; microthrombi, which were composed of fibrin and occasionally of fibrin and platelets; and extravasated erythrocytes and fibrin strands in the interstitium. One of the two patients also exhibited unusual nuclear alterations, which were characterized by replacement of normal chromatin by palely stained fibrous and filamentous material. Clinicopathologic analysis strongly suggested that the fatal cardiotoxicity in both patients resulted primarily from effects of high doses of cyclophosphamide, which were administered as part of a four drug regimen that provided tumor ablation and immunosuppression for bone marrow transplantation. Our findings emphasize the need for less toxic antineoplastic and immunosuppressive therapy for use in bone marrow transplantation procedures.