Irradiation of peripheral blood mononuclear cells with 7.5 Gy X-rays prior to donor lymphocyte infusion inhibits proliferation while preserving cytotoxicity and improves the effectiveness of HSCT in patients with hematological malignancies

摘要

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 in vitro 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.