Weiss L, Reich S, Slavin S
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Bone Marrow Transplant. 1990 Oct;6(4):229-33.
The effect of post-transplant immunosuppressive agents used in anti-GVHD prophylaxis on leukemic relapse was tested using a murine model of originally spontaneous, subsequently transplantable and non-immunogenic B cell leukemia (BCL1). (BALB/c x C57BL/6)F1 mice inoculated with 10(7) BCL1 cells were conditioned by total lymphoid irradiation (TLI) (1600 cGy), cyclophosphamide (200 mg/kg) or total body irradiation (TBI) 750 cGy and reconstituted with C57BL/6 (C57) bone marrow cells (30 x 10(6] or 10 x 10(6) bone marrow cells with additional 2 x 10(6) donor-type spleen cells, respectively. Mice were treated by cyclosporine A (CSA) 20 mg/kg i.p., or methylprednisolone (MP) 10 mg/kg i.p. for 10 days each and one group of controls received no post-transplant therapy. Stable chimerism was documented in all recipients with greater than or equal to 90% donor-type C57 cells in the peripheral blood. Eighty-nine percent of the mice treated by CSA following conditioning with TLI developed leukemia within 70 days, whereas none of the MP-treated mice and none of untreated chimeras showed any evidence of leukemia for more than 150 days. Adoptive transfer experiments using 10(5) spleen cells obtained from recipients conditioned with TBI were done to monitor residual leukemic cells following different post-transplant treatments. Eight-five percent of recipients of spleen cells obtained from mice treated with CSA developed leukemia in contrast with 33% and 25% when spleen cells were obtained from mice treated with MP or untreated controls, respectively (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
利用最初自发、随后可移植且无免疫原性的B细胞白血病（BCL1）小鼠模型，测试了用于预防移植物抗宿主病（GVHD）的移植后免疫抑制剂对白血病复发的影响。用10⁷个BCL1细胞接种的（BALB/c×C57BL/6）F1小鼠，通过全身淋巴照射（TLI）（1600 cGy）、环磷酰胺（200 mg/kg）或全身照射（TBI）750 cGy进行预处理，然后分别用30×10⁶或10×10⁶个骨髓细胞以及额外的2×10⁶个供体类型的脾细胞进行C57BL/6（C57）骨髓细胞重建。小鼠分别接受腹腔注射20 mg/kg环孢素A（CSA）或10 mg/kg甲泼尼龙（MP），各治疗10天，一组对照组未接受移植后治疗。所有接受者外周血中供体类型C57细胞大于或等于90%，证明嵌合状态稳定。用TLI预处理后接受CSA治疗的小鼠中，89%在70天内发生白血病，而接受MP治疗的小鼠和未治疗的嵌合体在超过150天内均未显示白血病迹象。进行过继转移实验，使用从接受TBI预处理的受体获得的10⁵个脾细胞，以监测不同移植后治疗后的残留白血病细胞。从接受CSA治疗的小鼠获得的脾细胞的受体中，85%发生白血病，而从接受MP治疗的小鼠或未治疗的对照组获得脾细胞时，这一比例分别为33%和25%（p = 0.0001）。（摘要截短于250字）
