Moriyama Y, Goto T, Hashimoto S, Nikkuni K, Saito H, Kishi K, Takahashi M, Shibata A, Endo K
First Department of Internal Medicine, Niigata University of School of Medicine, Japan.
Bone Marrow Transplant. 1993 Jun;11(6):437-41.
To develop new purging regimens for ABMT the ability to predict potential for purging of tumor cells from BM is important. Since the sensitivity of human B cell lymphoma to hyperthermia is not known, we examined its effect on the growth of B cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate potential for purging clonogenic tumor cells from normal marrow by heat, using a limiting dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal BM. When exposed to heat (42-43 degrees C) for 120 min, both clonogenic Raji and Daudi cells were dramatically reduced (a 4-to-6 log reduction) with time, whereas at 42 degrees C over half and at 43 degrees C 10% of normal granulocyte-macrophage progenitor cells survived for the same time period. This high level of lymphoma cell depletion by heat correlated with that of immunologic and pharmacologic studies. In addition, these survival curves during heating were found to correlate with the Gompertz-Makeham formula--a law of human mortality. This formula may be useful in predicting the purging effect of heat. These results suggest that in vitro hyperthermia could be applied effectively for the elimination of residual, clonogenic lymphoma cells in autologous marrow grafts before ABMT.
为开发用于自体骨髓移植（ABMT）的新净化方案，预测从骨髓中清除肿瘤细胞的潜力非常重要。由于人类B细胞淋巴瘤对热疗的敏感性尚不清楚，我们检测了热疗对B细胞淋巴瘤细胞系（Raji和Daudi）体外生长的影响，以评估通过热疗从正常骨髓中清除克隆性肿瘤细胞的潜力，采用极限稀释法测量在20倍过量正常骨髓中肿瘤细胞的对数减少情况。当暴露于42 - 43摄氏度的热环境中120分钟时，克隆性Raji和Daudi细胞数量随时间显著减少（减少4至6个对数级），而在42摄氏度时超过半数且在43摄氏度时10%的正常粒-巨噬细胞祖细胞在相同时间段内存活。热疗导致的淋巴瘤细胞高度清除与免疫和药理学研究结果相关。此外，发现加热过程中的这些存活曲线与冈珀茨-马凯姆公式（一种人类死亡率定律）相关。该公式可能有助于预测热疗的净化效果。这些结果表明，在ABMT前，体外热疗可有效用于清除自体骨髓移植物中残留的克隆性淋巴瘤细胞。
