TRANSFORMING GROWTH-FACTOR-BETA AS A PREDICTOR OF LIVER AND LUNG FIBROSIS AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ADVANCED BREAST-CANCER
TRANSFORMING GROWTH-FACTOR-BETA AS A PREDICTOR OF LIVER AND LUNG FIBROSIS AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ADVANCED BREAST-CANCER
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DOI：
10.1056/nejm199306033282203
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发表时间：
1993-06-03
影响因子：
158.5
通讯作者：
JIRTLE, RL
中科院分区：
文献类型：
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作者：
ANSCHER, MS;PETERS, WP;JIRTLE, RL
背景肝静脉阻塞性疾病和特发性间质性肺炎是骨髓移植后发病和死亡的主要原因。纤维化是这两种疾病的特征，并且转化生长因子β（TGF β）已经涉及纤维化的发病机制。我们使用酸乙醇提取法去除人血浆中的TGF β，并采用水貂肺上皮细胞生长抑制试验测量TGF β活性，定量测定了10名正常受试者和41名患者接受大剂量化疗和自体骨髓移植治疗晚期乳腺癌前后的血浆TGF β。结果。对照组和移植后未患肝静脉闭塞性疾病或特发性间质性肺炎的患者之间移植前TGF β水平没有差异。相比之下，肝静脉闭塞性疾病或特发性间质性肺炎患者的移植前TGF β水平显著高于对照组或无这些疾病的患者。当移植前血浆TGF β水平高于对照组平均水平2个标准差以上时，这两种情况的预测值均为90%或更高。诱导化疗后、大剂量化疗和自体骨髓移植前测量的血浆TGF β浓度与这些治疗后肝静脉闭塞性疾病和特发性间质性肺炎的风险密切相关。
Background. Hepatic veno-occlusive disease and idiopathic interstitial pneumonitis are major causes of morbidity and mortality after bone marrow transplantation. Fibrosis is a characteristic of both conditions, and transforming growth factor beta (TGFbeta) has been implicated in the pathogenesis of fibrosis.Methods. Using acid-ethanol extraction to remove TGFbeta from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGFbeta activity, we quantified plasma TGFbeta in 10 normal subjects and 41 patients before and after they underwent high-dose chemotherapy and autologous bone marrow transplantation for advanced breast cancer.Results. There was no difference in pretransplantation TGFbeta levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interstitial pneumonitis after transplantation. In contrast, pretransplantation TGFbeta levels were significantly higher in patients in whom hepatic veno-occlusive disease or idiopathic interstitial pneumonitis developed than in the controls or the patients without these conditions. The predictive value for the development of either condition was 90 percent or more when pretransplantation plasma TGFbeta levels were more than 2 SD above the mean established in the controls.Conclusions. The plasma TGFbeta concentration measured after induction chemotherapy but before high-dose chemotherapy and autologous bone marrow transplantation strongly correlates with the risk of hepatic veno-occlusive disease and idiopathic interstitial pneumonitis after these treatments.