Buja L M, Ferrans V J, Graw R G
Hum Pathol. 1976 Jan;7(1):17-45. doi: 10.1016/s0046-8177(76)80004-4.
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.
对29例白血病、再生障碍性贫血或转移性癌症患者进行了尸检，这些患者接受了消融治疗后进行了骨髓移植，其中22例患者的心脏病理结果进行了分析。一些心脏改变与未接受骨髓移植的血液系统和肿瘤疾病患者相似，包括心脏肥大、心脏萎缩、出血、因败血症或肝衰竭相关休克导致的坏死灶、系统性念珠菌病或葡萄球菌感染继发的心肌脓肿、纤维蛋白性心包炎和含铁血黄素沉着症。其他心脏改变则更具体地与移植手术相关因素有关。6例患者表现出一种独特的间质反应性改变，其特征为：（1）存在中等数量至大量的阿绍夫细胞，单独出现或形成小细胞聚集体，还有组织细胞、具有阿绍夫型细胞核的组织细胞样细胞、淋巴细胞和浆细胞；（2）在心脏血管和心内膜平滑肌、内皮细胞和施万细胞以及偶尔的心肌细胞中存在阿绍夫型细胞核。这种改变可能是由异常免疫机制引起的，因为观察到6例间质改变患者中有5例有移植物抗宿主病的临床证据。2例患者在移植后早期发生致命性充血性心力衰竭，并表现出心肌损伤，其组织学和移植后特征表明存在严重急性损伤。这2例患者的表现包括坏死的肌细胞，其呈现多条收缩带、耐淀粉酶的PAS染色和细胞内纤维蛋白沉积；微血栓，由纤维蛋白组成，偶尔由纤维蛋白和血小板组成；以及间质内渗出的红细胞和纤维蛋白丝。2例患者中的1例还表现出异常的核改变，其特征是正常染色质被淡染的纤维状和丝状物质取代。临床病理分析强烈提示，这2例患者的致命心脏毒性主要源于高剂量环磷酰胺的作用，环磷酰胺作为四药方案的一部分给药，该方案用于为骨髓移植提供肿瘤消融和免疫抑制。我们的研究结果强调了在骨髓移植手术中需要使用毒性较小的抗肿瘤和免疫抑制疗法。
