Charak B S, Brynes R K, Chogyoji M, Kortes V, Tefft M, Mazumder A
Bone Marrow Transplantation Program, Georgetown University, Washington, D.C. 20007.
Transplantation. 1993 Jul;56(1):31-7. doi: 10.1097/00007890-199307000-00006.
IL-2 has been used after autologous BMT (ABMT) with the aim of inducing graft versus leukemia (GVL) effect. Our studies in mice have shown that IL-2 therapy induces GVL effect when employed after BMT with bone marrow (BM) that has been activated with IL-2 in vitro (ABM). The present study was carried out to define the time of optimal GVL effect after BMT so that the immunomodulatory approaches could be concentrated at the time of maximum GVL effect. Our data show that GVL effect was induced if IL-2 was instituted immediately after BMT with ABM in mice with acute myeloid leukemia; institution of IL-2 1 week after BMT with ABM did not induce GVL effect. IL-2 therapy instituted immediately or 1 week after BMT with fresh bone marrow (FBM) did not induce any GVL effect. A significant increase in the NK activity was noticed whether IL-2 was instituted immediately or 1 week after BMT, either with FBM or with ABM. To evaluate the ability of IL-2 in the eradication of residual disease from the autograft and the host, BM with variable infiltration with leukemia was activated with IL-2 and used for BMT in leukemic mice. The GVL effect of BM with minimal leukemic infiltration (absence of morphologically demonstrable disease) was comparable to the GVL effect of normal BM. These findings suggest that: (a) maximum GVL effect after BMT with ABM is concentrated in the early post-transplant period possibly because of minimal residual disease during this time; (b) an increase in the NK activity induced by IL-2 therapy may not predict for an improved GVL effect; and (c) for optimum GVL effect, BM with minimal leukemic infiltration should be activated with IL-2 before BMT.
白细胞介素-2（IL-2）已被用于自体骨髓移植（ABMT）后，目的是诱导移植物抗白血病（GVL）效应。我们在小鼠身上的研究表明，当在体外经IL-2激活的骨髓（BM）进行骨髓移植（BMT）后使用IL-2治疗时，可诱导GVL效应（ABM）。本研究旨在确定骨髓移植后最佳GVL效应的时间，以便免疫调节方法能够集中在GVL效应最大的时候。我们的数据表明，如果在急性髓性白血病小鼠中进行ABM骨髓移植后立即给予IL-2，可诱导GVL效应；在ABM骨髓移植后1周给予IL-2则不能诱导GVL效应。在新鲜骨髓（FBM）骨髓移植后立即或1周给予IL-2治疗均未诱导出任何GVL效应。无论在BMT后立即还是1周给予IL-2，无论是使用FBM还是ABM，自然杀伤细胞（NK）活性均显著增加。为了评估IL-2清除自体移植物和宿主中残留疾病的能力，用IL-2激活含有不同白血病浸润程度的骨髓，并将其用于白血病小鼠的骨髓移植。白血病浸润极少（无形态学可证实的疾病）的骨髓的GVL效应与正常骨髓的GVL效应相当。这些发现表明：（a）ABM骨髓移植后的最大GVL效应集中在移植后的早期，可能是因为此时残留疾病极少；（b）IL-2治疗诱导的NK活性增加可能无法预测GVL效应的改善；（c）为了获得最佳的GVL效应，在骨髓移植前应使用IL-2激活白血病浸润极少的骨髓。
