Wingard J R, Mellits E D, Jones R J, Beschorner W E, Sostrin M B, Burns W H, Santos G W, Saral R
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Bone Marrow Transplant. 1989 Nov;4(6):685-9.
Hepatic veno-occlusive disease (HVOD) and interstitial pneumonitis (IP) are both widely regarded as toxicities of intensive cytoreductive therapy, but their association has not been previously examined. Risk factors for IP were evaluated in 154 patients given intensive cytoreductive therapy followed by allogeneic bone marrow transplantation during a 2 1/2 year period. IP occurred in 68 patients; HVOD occurred in 39. The actuarial incidence of IP in patients with VOD was 71% and 45% in those without VOD (p = 0.0002). In multivariate analysis, the diagnosis of hematologic malignancy (p less than 0.001), the occurrence of HVOD (p less than 0.01), and pretransplant CMV seropositivity (p less than 0.02) were significantly associated with IP. The individual relative risks for IP of presence to absence of these factors was 4.5 for the diagnosis of hematologic malignancy, 2.1 for HVOD, and 1.9 for CMV seropositivity. Pulmonary veno-occlusive disease (PVOD), a previously rare observation, was noted at autopsy in 1/5 (20%) patients with HVOD alone, 6/20 (30%) patients with IP alone, and 10/14 (71%) of patients with both HVOD and IP. The association of HVOD and IP is supportive of the concept that toxic effects of cytotoxic therapy have a major role in pathogenesis of HVOD and IP.
肝静脉闭塞病（HVOD）和间质性肺炎（IP）均被广泛认为是强化细胞减灭治疗的毒性反应，但此前尚未对它们之间的关联进行过研究。在2年半的时间里，对154例接受强化细胞减灭治疗后进行异基因骨髓移植的患者评估了IP的危险因素。68例患者发生了IP；39例发生了HVOD。发生HVOD的患者中IP的精算发病率为71%，未发生HVOD的患者中为45%（p = 0.0002）。多变量分析显示，血液系统恶性肿瘤的诊断（p < 0.001）、HVOD的发生（p < 0.01）以及移植前巨细胞病毒血清学阳性（p < 0.02）与IP显著相关。这些因素存在与不存在时IP的个体相对风险分别为：血液系统恶性肿瘤的诊断为4.5，HVOD为2.1，巨细胞病毒血清学阳性为1.9。肺静脉闭塞病（PVOD）此前很少见，在尸检中发现，单独发生HVOD的患者中有1/5（20%）、单独发生IP的患者中有6/20（30%）以及同时发生HVOD和IP的患者中有10/14（71%）存在PVOD。HVOD和IP之间的关联支持了细胞毒性治疗的毒性作用在HVOD和IP发病机制中起主要作用这一概念。
