Kim Hee-Je, Kim Tai-Gyu, Cho Hyun Il, Han Hoon, Min Woo-Sung, Kim Chun-Choo
Department of Internal Medicine, Catholic Hemopoietic Stem Cell Transplantation Center, The Catholic University of Korea, Seoul, Korea.
Int J Hematol. 2002 Nov;76(4):370-5. doi: 10.1007/BF02982699.
To evaluate the clinical implications of a mixed lymphocyte reaction between leukemic cells and lymphocytes from HLA-matched sibling donors, we attempted to generate donor-derived, graft-versus-leukemia-effective cells and to define their characteristics. We studied 8 patients with chronic myelogenous leukemia (CML), including 5 patients in the chronic phase (CP), 3 patients in the accelerated phase (AP), and 2 patients with acute myelogenous leukemia (AML) in their first complete remission. Cells from these patients were used as stimulators in a mixed lymphocyte reaction.The effects of natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs) were separated by observing tests for cytotoxicity to target cells, including K562 cells, the patient's leukemic cells, and phytohemagglutinin (PHA) blasts. Donor-derived antileukemic CTLs againstthe patient's own leukemic cells are productive in vitro. The efficacy of generating CTLs against leukemic target cells was (in decreasing order) AML, CML-CP, and CML-AP. Cytotoxic activity against leukemic targets was prominent in 4 cases--2 CML-CP and the 2 AML cases. On the contrary, the 3 cases of CML-AP showed low CTL activity. In cases showing 1 positive result among 3 targets (K562 cells, the patient's leukemic cells, and PHA blasts), the relapse rate was significantly lower (P = .022) on follow-up (median, 33 months; 7-40 months) after hematopoietic stem cell transplantation. By a combined analysis of the cytotoxicity effects for all 3 target cells, we were able to demonstrate a correlation between leukemic relapse and the variable degree of the cytotoxicity test results. Although the total sample numbers for this study were low, we speculate that these results may come from differences in the individual characteristics of the leukemic cells that are in line with their clinical disease status.
为评估白血病细胞与 HLA 配型相合的同胞供者淋巴细胞之间混合淋巴细胞反应的临床意义，我们试图生成供者来源的、具有移植物抗白血病效应的细胞并明确其特征。我们研究了 8 例慢性髓性白血病（CML）患者，包括 5 例慢性期（CP）患者、3 例加速期（AP）患者以及 2 例处于首次完全缓解期的急性髓性白血病（AML）患者。这些患者的细胞被用作混合淋巴细胞反应中的刺激细胞。通过观察对包括 K562 细胞、患者白血病细胞和植物血凝素（PHA）刺激的淋巴细胞在内的靶细胞的细胞毒性试验，分离出自然杀伤（NK）细胞和细胞毒性 T 淋巴细胞（CTL）的作用。针对患者自身白血病细胞的供者来源抗白血病 CTL 在体外具有活性。生成针对白血病靶细胞的 CTL 的效力依次为 AML、CML-CP 和 CML-AP。4 例患者（2 例 CML-CP 和 2 例 AML）对白血病靶细胞具有显著的细胞毒性活性。相反，3 例 CML-AP 患者的 CTL 活性较低。在对 3 种靶细胞（K562 细胞、患者白血病细胞和 PHA 刺激的淋巴细胞）检测结果中出现 1 个阳性结果的患者中，造血干细胞移植后随访（中位时间 33 个月；7 - 40 个月）时复发率显著较低（P = 0.022）。通过对所有 3 种靶细胞的细胞毒性作用进行综合分析，我们能够证明白血病复发与细胞毒性试验结果的不同程度之间存在相关性。尽管本研究的样本总数较少，但我们推测这些结果可能源于白血病细胞个体特征的差异，这与它们的临床疾病状态相符。
