Wei Yong-Qiu, Cen Xi-Nan, Liu Hui-Hui, Sun Yu-Hua, Shi Yong-Jin, Liu Wei, Dong Yu-Jun, Ren Han-Yun
Department of Hematology, Peking University First Hospital, Beijing 100034, P.R. China.
Oncol Lett. 2017 Jun;13(6):4101-4108. doi: 10.3892/ol.2017.5966. Epub 2017 Mar 31.
The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7.5, 10, 15, 25 or 50 Gy, and their proliferative activity was determined using a WST-8 assay kit. The cytotoxic activity of non-irradiated PBMCs and PBMCs irradiated with 7.5 Gy X-rays was tested in the leukemic cell line K562 and its Adriamycin-resistant strain K562A using a lactate dehydrogenase assay. The clinical data of 7 patients who received 7.5 Gy X-ray-irradiated PBMC infusions following autologous HSCT were analyzed. PBMCs irradiated with ≥7.5 Gy X-rays exhibited a complete inhibition of proliferation. PBMCs irradiated with 7.5 Gy X-rays exhibited significantly increased cytotoxic activity towards K562 cells compared with K562A cells (P<0.05). There was no significant difference in cytotoxicity between irradiated and non-irradiated PBMCs, irrespective of the target cell, K562 or K562A (P>0.05). Based on the data, clinical data from patients who received 7.5 Gy X-ray-irradiated PBMC infusions following HSCT between January 2005 and January 2013 were assessed retrospectively. A total of 7 patients were included in the current study. The majority achieved various degrees of remission following donor lymphocyte infusion (DLI) and none suffered from GVHD. This indicates that 7.5 Gy-irradiated PMBCs have a potential application in DLI for the treatment of patients following HSCT. However, further studies on larger patient cohorts are required to assess the clinical potential of 7.5 Gy-irradiated PBMCs for preserving the GVT effect while avoiding GVHD following HSCT.
本研究的目的是探讨不同剂量X射线对外周血单个核细胞（PBMC），尤其是淋巴细胞的增殖和细胞毒性活性的影响，以评估这是否能降低造血干细胞移植（HSCT）后血液系统恶性肿瘤患者移植物抗宿主病（GVHD）的发生率，同时保留移植物抗肿瘤（GVT）效应。用0、2.5、5、7.5、10、15、25或50 Gy剂量的X射线照射健康供者的PBMC，并使用WST-8检测试剂盒测定其增殖活性。使用乳酸脱氢酶检测法在白血病细胞系K562及其阿霉素耐药株K562A中检测未照射的PBMC和经7.5 Gy X射线照射的PBMC的细胞毒性活性。分析了7例自体HSCT后接受7.5 Gy X射线照射的PBMC输注患者的临床数据。≥7.5 Gy X射线照射的PBMC表现出增殖完全抑制。与K562A细胞相比，经7.5 Gy X射线照射的PBMC对K562细胞的细胞毒性活性显著增加（P<0.05）。无论靶细胞是K562还是K562A，照射和未照射的PBMC之间的细胞毒性均无显著差异（P>0.05）。基于这些数据，回顾性评估了2005年1月至2013年1月HSCT后接受7.5 Gy X射线照射的PBMC输注患者的临床数据。本研究共纳入7例患者。大多数患者在供体淋巴细胞输注（DLI）后达到不同程度的缓解，且无一例发生GVHD。这表明7.5 Gy照射的PMBC在HSCT后患者的DLI治疗中具有潜在应用价值。然而，需要对更大的患者队列进行进一步研究，以评估7.5 Gy照射的PBMC在HSCT后保留GVT效应同时避免GVHD的临床潜力。
