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High Epstein–Barr virus-specific T-cell counts are associated with near-zero likelihood of acute myeloid leukemia relapse after hematopoietic cell transplantation

Leukemia volume 26, pages 359–362 (2012)Cite this article

The main cause of allogeneic hematopoietic cell transplant (HCT) failure is a disease relapse, which occurs in 15–55% of patients undergoing HCT for acute myeloid leukemia (AML).1 Decreased incidence of malignancy relapse has been observed in patients who develop graft versus host disease (GVHD), presumably due to a concomitant graft-versus-leukemia/lymphoma (GVL) reaction. T cells are believed to have a major role in the GVL reaction.2 A small study has shown that leukemia antigen-specific T cells can be detected after HCT and that they are associated with decreased malignancy relapse.3 However, only few leukemia specific antigens are known. A surrogate marker of the GVL response could, theoretically, be used instead. This could be the immune response to another endogenous antigen like an antigen from a persisting virus (for example, a herpesvirus) that infected the recipient long before the transplantation. Parkman et al, showed an association between high proliferative response of mononuclear cells (MNCs) to herpesvirus lysate and decreased risk of relapse.4 However, they included only cord blood transplant recipients, which accounts for a minority of HCT recipients, did not assess which MNC subset is associated with relapse, and did not assess whether the proliferative response could be used as a predictive marker of relapse. Here, we developed and tested in marrow or filgrastim-mobilized blood stem cell recipients the predictive value of assays enumerating subsets of herpesvirus-specific T cells. The subsets were defined by surface marker expression (CD4 or CD8) and their ability to proliferate or produce interleukin-2 (IL2), interferon gamma (IFNγ) and/or tumor necrosis factor-α (TNFα) upon stimulation with viral antigens. To enable evaluation of the majority of patients we measured T cells specific for the three most prevalent herpesviruses, that is, Epstein–Barr virus (EBV), human herpesvirus 6 (HHV6) and Varicella–zoster virus (VZV).

We studied 42 AML patients. There were no statistically significant differences in clinical/demographic characteristics of patients who did versus did not relapse (Supplementary Table 1). Minimum follow-up for relapse of non-relapse patients was 2 years (important, as most relapses occur in the first 2 years post transplant), except for two patients who were lost to follow-up on days 435 and 470 post transplant. On day 56, we enumerated 98 herpesvirus-specific T-cell subsets secreting cytokines after 18 h stimulation (‘18 h assay’), and 14 subsets proliferating after 7-day stimulation (‘7 d assay’). For details, see the Patients and Methods section in Supplementary Material, Supplementary Figures 1–3 and Supplementary Table 6.

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Authors and Affiliations

  1. University of Calgary, Calgary, Alberta, Canada

    M Hoegh-Petersen, S Sy, A Ugarte-Torres, T S Williamson, M Eliasziw, Y Liu, S Liu, P Podgorny, F Khan & J Storek

  2. Alberta Health Services, Calgary, Alberta, Canada

    A Mansoor, P R Duggan, D A Stewart, J A Russell & J Storek

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  1. M Hoegh-Petersen
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  2. S Sy
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Correspondence to M Hoegh-Petersen.

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Additional information

Published as an abstract at the Americal Society of Hematology meeting (Orlando, FL, December 2010), an abstract at the American Society for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research Tandem meeting (Honolulu, HI, February 2011), and Mette Hoegh-Petersen's Master Degree Thesis at the website of the National Library of Canada, www.nlc-bnc.ca.

Supplementary Information accompanies the paper on the Leukemia website

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Hoegh-Petersen, M., Sy, S., Ugarte-Torres, A. et al. High Epstein–Barr virus-specific T-cell counts are associated with near-zero likelihood of acute myeloid leukemia relapse after hematopoietic cell transplantation. Leukemia 26, 359–362 (2012). https://doi.org/10.1038/leu.2011.195

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