少量多次异基因骨髓移植的实验研究

Experimental study on multiple-low-dose cell allogeneic bone marrow transplantation

目的：探讨少量多次异基因骨髓移植的ＧＶＨＤ反应。方法：采用不同少量异基因骨髓细胞的多次尾静脉注射。观察大小便，皮毛，体位及死亡率等ＧＶＨＤ反应一般表现。移植后不同天数进行体内混合淋巴细胞反应及嵌合体测定。外周血象及骨髓有核细胞按常规方法计数。半固体琼脂法进行骨髓ＣＦＵ－ＧＭ测定。肝、脾、小肠及皮肤病理学检查判断ＧＶＨＤ反应程度。外周血Ｌ６１５细胞及脾脏Ｌ６１５细胞比例判断ＧＶＬ作用。结果：一次性大剂量组ＧＭＨＤ反应表现明显，单纯多次异基因骨髓细胞移植的ＧＶＨＤ反应不明显，而少量多次骨髓移植组则ＧＶＨＤ反应强度界于两者之间，并且具有较好的造血恢复作用。在ＧＶＬ作用方面，一次性大剂量骨髓移植组产生较强的近期抗白血病作用，但多死于ＧＶＨＤ反应。少量多次骨髓移植１×１０６骨髓细胞及 １×１０６脾单个核细胞组抗白血病作用较强，３０ ｄ生存率达 ６０％，死亡原因主要为白血病。结论：少量多次骨髓移植可以减轻ＧＶＨＤ反应，保留部分ＧＶＬ作用。

Objective:To study the graft-versus-host response in multiple-low-dose cell allogeneic bone marrow transplantion(BMT)Methods: Varied multiple-low-dose allogeneic bone marrow cells were given to the recipient mice intravenously through the tail vein. The urine and feces, fur, posture as well as mortality, etc. were observed. Mixed lymphocyte response and chimerism were measured on day 4. Complete blood cells and bone marrow nucleated cells were counted as usual. CFU-GM was measured using the semi-solid agar method. Pathological abnormalities of the liver, spleen, intestine and skin were examined to evaluate the seventies of GVHD. The proportion of L615 cells in peripheral blood and spleen cells were used to estimate the graft-versus-leukemia effect. Results: Apparent graft-versus-host (GVH) response w seen in one mega-dose cell group, and slight GVH response in multiple mega-dose cell group. Moderate GVH response was seen in the mull pie low-dose cell group, and hemopoietic recovery was relatively rapid. In aspect of graft-versus-leukemia,a relatively extensive short-term anti-leukemic effects were observed in one mega-dose cell bone marrow transplantation group, but most mice died of GVHD. GVL effects were s so observed in multiple low-dose bone marrow cell transplantation group. Sumval rate on day 30 was 60%, most mice died of leukemia. Condusion:GVL effects were remained and GVHD were reduced in the setting of multiple low dose cell Allo-BMT.