Hartmann D W, Robinson W A, Morton N J, Mangalik A, Glode L M
Blut. 1981 Apr;42(4):209-20. doi: 10.1007/BF00996750.
In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1--5.5 x 10(5) committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 10 x 10(9)/l and thrombocytopenia of less than 50.0 x 10(9)/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.
在一项I期试验中，晚期恶性黑色素瘤患者接受了高剂量氮芥（HN2）和自体骨髓移植治疗。三名患者进入该方案。在每千克体重采集1.1--5.5 x 10(5)个定向干细胞（CFU-C）后，静脉推注33 mg/m2的HN2。48小时后，将未冷冻保存的骨髓静脉回输。副作用包括恶心、呕吐、厌食、脱发、静脉炎、肝毒性和神经毒性。心脏毒性和低钙血症是使用较低剂量HN2时未出现过的意外副作用。粒细胞减少至低于10 x 10(9)/l和血小板减少至低于50.0 x 10(9)/l分别平均持续10天和8天。三名患者中有两名存在可测量的疾病，对本方案中使用的HN2剂量无反应。该研究表明，血液学恢复时间比以前在未进行自体骨髓移植的HN2研究中报告的要短。然而，该剂量HN2的非血液学副作用严重，排除了使用更高剂量的可能性。
