Gassmann W, Erbersdobler A, Uharek L, Glass B, Löffler H, Mueller-Ruchholtz W
2nd Department of Internal Medicine, University of Kiel, Federal Republic of Germany.
J Cancer Res Clin Oncol. 1991;117 Suppl 4(Suppl 4):S224-7. doi: 10.1007/BF01613232.
We have tested ifosfamide and ACNU for their effectiveness in preventing graft rejection following allogeneic bone marrow transplantation. The engraftment-promoting potency of both was compared to that of the standard agent cyclophosphamide. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) (CAP x LEW) F1 marrow cells, which are unable to induce a graft vs host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte count either until death of the animal or until day 80. Surviving animals received a donor-type skin graft to confirm the persistence of allogeneic haematopoiesis. Because of its weak immunosuppressive properties, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, ifosfamide and ACNU and cyclophosphamide as the standard agent could be tested for their capacity to prevent marrow graft rejection. The following rejection rates were observed: cyclophosphamide: 30 mg/kg 100%, 60 mg/kg 60%, 90 mg/kg 20%, 120 mg/kg and 180 mg/kg 0%; ACNU: 3, 5, 7, and 10 mg/kg 100%, 15 mg/kg 45%, 20 and 30 mg/kg 0%; ifosfamide: 60-120 mg/kg 100%, 180 mg/kg 68%, 240 and 360 mg/kg 0%. Thus, 240 mg/kg ifosfamide or 20 mg/kg ACNU is nearly equivalent to the standard dose of 120 mg/kg cyclophosphamide in engraftment-promoting potency in allogeneic bone marrow transplantation.
我们测试了异环磷酰胺和嘧啶亚硝脲在预防异基因骨髓移植后移植物排斥反应方面的有效性。将二者促进植入的效力与标准药物环磷酰胺进行了比较。给LEW大鼠注射致死剂量（35mg/kg）的白消安，随后注射1×10⁸ （CAP×LEW）F1骨髓细胞，这些细胞在LEW受体中无法诱导移植物抗宿主反应。通过监测血细胞比容和粒细胞计数来评估骨髓移植物的排斥情况，直至动物死亡或直至第80天。存活的动物接受供体类型的皮肤移植，以确认异基因造血的持续存在。由于白消安自身的免疫抑制特性较弱，其本身无法使异基因骨髓植入。因此，可以测试异环磷酰胺、嘧啶亚硝脲以及作为标准药物的环磷酰胺预防骨髓移植物排斥的能力。观察到以下排斥率：环磷酰胺：30mg/kg为100%，60mg/kg为60%，90mg/kg为20%，120mg/kg和180mg/kg为0%；嘧啶亚硝脲：3、5、7和10mg/kg为100%，15mg/kg为45%，20和30mg/kg为0%；异环磷酰胺：60 - 120mg/kg为100%，180mg/kg为68%，240和360mg/kg为0%。因此，在异基因骨髓移植中，240mg/kg的异环磷酰胺或20mg/kg的嘧啶亚硝脲在促进植入效力方面几乎等同于120mg/kg环磷酰胺的标准剂量。
