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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

  • Authors:
    • Yong‑Qiu Wei
    • Xi‑Nan Cen
    • Hui‑Hui Liu
    • Yu‑Hua Sun
    • Yong‑Jin Shi
    • Wei Liu
    • Yu‑Jun Dong
    • Han‑Yun Ren
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Peking University First Hospital, Beijing 100034, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4101-4108
    |
    Published online on: March 31, 2017
       https://doi.org/10.3892/ol.2017.5966
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Abstract

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.
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1 

Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Zhang XH, Chen YH, Han W, Wang FR, Wang JZ, et al: Prevention of relapse using granulocyte CSF-primed PBPCs following HLA-mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: A retrospective risk-factor analysis. Bone Marrow Transplant. 47:1099–1104. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Hasskarl J, Zerweck A, Wäsch R, Ihorst G, Bertz H and Finke J: Induction of graft versus malignancy effect after unrelated allogeneic PBSCT using donor lymphocyte infusions derived from frozen aliquots of the original graft. Bone Marrow Transplant. 47:277–282. 2012. View Article : Google Scholar : PubMed/NCBI

3 

El-Cheikh J, Crocchiolo R, Furst S, Ladaique P, Castagna L, Faucher C, Granata A, Oudin C, Lemarie C, Calmels B, et al: Lenalidomide plus donor-lymphocytes infusion after allogeneic stem-cell transplantation with reduced-intensity conditioning in patients with high-risk multiple myeloma. Exp Hematol. 40:521–527. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Deol A and Lum LG: Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev. 36:528–538. 2010. View Article : Google Scholar : PubMed/NCBI

5 

McLarnon A, Piper KP, Goodyear OC, Arrazi JM, Mahendra P, Cook M, Clark F, Pratt G, Craddock C and Moss PA: CD8(+) T-cell immunity against cancer-testis antigens develops following allogeneic stem cell transplantation and reveals a potential mechanism for the graft-versus-leukemia effect. Haematologica. 95:1572–1578. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Oettel KR, Wesly OH, Albertini MR, Hank JA, Iliopolis O, Sosman JA, Voelkerding K, Wu SQ, Clark SS and Sondel PM: Allogeneic T-cell clones able to selectively destroy Philadelphia chromosome-bearing (Ph1+) human leukemia lines can also recognize Ph1- cells from the same patient. Blood. 83:3390–3402. 1994.PubMed/NCBI

7 

Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, Boulad F, Castro-Malaspina H, Childs BH, Gillio AP and Kernan NA: Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: Separation of graft-versus-leukemia responses from graft-versus-host disease. Blood. 86:1261–1268. 1995.PubMed/NCBI

8 

Dazzi F, Szydlo RM, Cross NC, Craddock C, Kaeda J, Kanfer E, Cwynarski K, Olavarria E, Yong A, Apperley JF and Goldman JM: Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood. 96:2712–2716. 2000.PubMed/NCBI

9 

British Committee for Standards in Haematology, ; Milkins C, Berryman J, Cantwell C, Elliott C, Haggas R, Jones J, Rowley M, Williams M and Win N: Guidelines for pre-transfusion compatibility procedures in blood transfusion laboratories. British Committee for Standards in Haematology. Transfus Med. 23:3–35. 2013. View Article : Google Scholar : PubMed/NCBI

10 

McGuirk JP, Seropian S, Howe G, Smith B, Stoddart L and Cooper DL: Use of rituximab and irradiated donor-derived lymphocytes to control Epstein-Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation. Bone Marrow Transplant. 24:1253–1258. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Tsirigotis P, Resnick IB, Kapsimalli V, Dray L, Psarra E, Samuel S, Spyridonidis A, Konsta E, Vikentiou M, Or R, et al: Irradiated mononuclear cells express significant in vitro cytotoxic activity: Promise for in vivo clinical efficacy of irradiated mismatched donor lymphocytes infusion. Immunotherapy. 6:409–417. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Reynolds JT, Watkins JM, Dufan TA and Kubsad SS: Irradiation of donor mononuclear cells for treatment of chemorefractory metastatic solid cancers: A community-based immune transplant pilot study. Cancer Res Treat. 44:133–141. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Wu BY, Song CY, Guo KY, Yan DA, Yang YL, Xiao LL and Wu GX: Treatment of malignant hematologic diseases by peripheral blood stem cell transplantation combined with halotype lymphocyte infusion. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 11:287–291. 2003.(In Chinese). PubMed/NCBI

14 

Pierelli L, Menichella G, Paoloni A, Teofili L, Sica S, Foddai ML, Rossi PL, Leone G, Mango G and Bizzi B: Collection of peripheral blood stem cells using an automated discontinuous flow blood cell separator. Haematologica. 75 Suppl 1:S29–S32. 1990.

15 

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J and Vardiman JW: WHO Classification of Tumors of the Haematopoietic and Lymphoid Tissues. 4th edition. IARC Press; Lyon: 2008

16 

Kolb HJ, Schmid C, Barrett AJ and Schendel DJ: Graft-versus-leukemia reactions in allogeneic chimeras. Blood. 103:767–776. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Xia G, Truitt RL and Johnson BD: Graft-versus-leukemia and graft-versus-host reactions after donor lymphocyte infusion are initiated by host-type antigen-presenting cells and regulated by regulatory T cells in early and long-term chimeras. Biol Blood Marrow Transplant. 12:397–407. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Kolb HJ: Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 112:4371–4383. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Stern M, Passweg JR, Meyer-Monard S, Esser R, Tonn T, Soerensen J, Paulussen M, Gratwohl A, Klingebiel T, Bader P, et al: Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: A prospective phase II study in two centers. Bone Marrow Transplant. 48:433–438. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Yun HD and Waller EK: Finding the sweet spot for donor lymphocyte infusions. Biol Blood Marrow Transplant. 19:507–508. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Porter DL, Collins RH Jr, Shpilberg O, Drobyski WR, Connors JM, Sproles A and Antin JH: Long-term follow-up of patients who achieved complete remission after donor leukocyte infusions. Biol Blood Marrow Transplant. 5:253–261. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Zoumbos NC and Spyridonidis A: High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transplant. 19:75–81. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Bar M, Sandmaier BM, Inamoto Y, Bruno B, Hari P, Chauncey T, Martin PJ, Storb R, Maloney DG, Storer B and Flowers ME: Donor lymphocyte infusion for relapsed hematological malignancies after allogeneic hematopoietic cell transplantation: Prognostic relevance of the initial CD3+ T cell dose. Biol Blood Marrow Transplant. 19:949–957. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Levine JE, Braun T, Penza SL, Beatty P, Cornetta K, Martino R, Drobyski WR, Barrett AJ, Porter DL, Giralt S, et al: Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 20:405–412. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Waller EK, Ship AM, Mittelstaedt S, Murray TW, Carter R, Kakhniashvili I, Lonial S, Holden JT and Boyer MW: Irradiated donor leukocytes promote engraftment of allogeneic bone marrow in major histocompatibility complex mismatched recipients without causing graft-versus-host disease. Blood. 94:3222–3233. 1999.PubMed/NCBI

26 

Nikiforow S and Alyea EP: Maximizing GVL in allogeneic transplantation: Role of donor lymphocyte infusions. Hematology Am Soc Hematol Educ Program. 2014:570–575. 2014.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wei YQ, Cen XN, Liu HH, Sun YH, Shi YJ, Liu W, Dong YJ and Ren HY: 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. Oncol Lett 13: 4101-4108, 2017.
APA
Wei, Y., Cen, X., Liu, H., Sun, Y., Shi, Y., Liu, W. ... Ren, H. (2017). 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. Oncology Letters, 13, 4101-4108. https://doi.org/10.3892/ol.2017.5966
MLA
Wei, Y., Cen, X., Liu, H., Sun, Y., Shi, Y., Liu, W., Dong, Y., Ren, H."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". Oncology Letters 13.6 (2017): 4101-4108.
Chicago
Wei, Y., Cen, X., Liu, H., Sun, Y., Shi, Y., Liu, W., Dong, Y., Ren, H."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". Oncology Letters 13, no. 6 (2017): 4101-4108. https://doi.org/10.3892/ol.2017.5966
Copy and paste a formatted citation
x
Spandidos Publications style
Wei YQ, Cen XN, Liu HH, Sun YH, Shi YJ, Liu W, Dong YJ and Ren HY: 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. Oncol Lett 13: 4101-4108, 2017.
APA
Wei, Y., Cen, X., Liu, H., Sun, Y., Shi, Y., Liu, W. ... Ren, H. (2017). 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. Oncology Letters, 13, 4101-4108. https://doi.org/10.3892/ol.2017.5966
MLA
Wei, Y., Cen, X., Liu, H., Sun, Y., Shi, Y., Liu, W., Dong, Y., Ren, H."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". Oncology Letters 13.6 (2017): 4101-4108.
Chicago
Wei, Y., Cen, X., Liu, H., Sun, Y., Shi, Y., Liu, W., Dong, Y., Ren, H."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". Oncology Letters 13, no. 6 (2017): 4101-4108. https://doi.org/10.3892/ol.2017.5966
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