Godder, KT, Henslee-Downey, PJ, Mehta, J, Park, BS, Chiang, KY, Abhyankar, S et al.. Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant 39: 751-757

South Carolina Cancer Center, Columbia, SC, USA.
Bone Marrow Transplantation (Impact Factor: 3.57). 06/2007; 39(12):751-7. DOI: 10.1038/sj.bmt.1705650
Source: PubMed


Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia. This is an eight-year follow-up to our previous study showing a survival advantage to patients with an increased gammadelta T cells following ASCT. gammadelta T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n = 77; acute myelogenous leukemia (AML) n = 76) undergoing partially mismatched related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity of three antigens was 37% in the graft-versus-host disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n = 46) or OKT3 (n = 107). Five years LFS and overall survival (OS) of patients with increased gammadelta compared to those with normal/decreased numbers were 54.4 vs 19.1%; P < 0.0003, and 70.8 vs 19.6% P < 0.0001, respectively, with no difference in GvHD (P = 0.96). In a Cox multivariate analysis, normal/decreased gammadelta (hazard ratio (HR) 4.26, P = 0.0002) and sex mismatch (HR 1.45 P=0.049) were associated with inferior LFS. In conclusion, gammadelta T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD. Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.


Available from: Lawrence S Lamb, Apr 04, 2014
  • Source
    • "In contrast to í µí»¼í µí»½ T-cells, í µí»¾í µí»¿ T-cell activation is not regulated by MHC molecules making them less likely to cause an HLA-dependent GVHD. The í µí»¾í µí»¿ T-cell subset has also been shown to provide a protective effect against leukemia relapse, making the exploitation of this cell subset an attractive alternative after HSCT [27] [28]. "

    Biology of Blood and Marrow Transplantation 02/2015; 21(2):S149-S150. DOI:10.1016/j.bbmt.2014.11.211 · 3.40 Impact Factor
  • Source
    • "In addition, a survival advantage to patients with an increased γδ T cells following allogeneic stem cell transplantation (ASCT) has been reported. A long-term survival advantage in a group of high-risk acute leukemia patients who recovered with increased number of circulating γδ T cells following partially mismatched related haematopoietic stem cell transplantation was reported68. "
    [Show abstract] [Hide abstract]
    ABSTRACT: γδ T lymphocytes represent a minor subset of peripheral blood in humans (<10%). γδ T cells expressing Vγ9Vδ2 T cell receptor recognise the endogenous pool of isopentenyl pyrophosphate (IPP) that is overproduced in cancer cells as a result of dysregulated mevalonate pathway. Aminobisphosphonates increase the endogenous pool of IPP in cells by blocking the enzyme farnesyl pyrophosphate synthase (FPPS) of the mevalonate pathway. Activated γδ T cells release copious amounts of interferon (IFN)-γ and tumour necrosis factor (TNF)-α and exhibit potent anti-tumour activity. Combination of γδ T cells with therapeutic monoclonal antibodies can efficiently mediate antibody dependent cellular cytotoxicity against tumours. These features makes γδ T cells attractive mediator of cancer immunotherapy. We review here, the basic properties and importance of γδ T cells in tumour immunity, and highlight the key advances in anti-tumour effector functions of γδ T cells achieved over the last few years and also summarize the results of the clinical trials that have been done till date. Future immunotherapeutic approach utilizing γδ T cells holds considerable promise for treatment of different types of cancer.
    The Indian Journal of Medical Research 11/2013; 138(5):755-61. · 1.40 Impact Factor
  • Source
    • "Vδ1+ T cells are activated by stress-induced self-antigens such as MIC-A/B and UL-16 binding proteins through the T cell receptor and NKG2D [19]–[21] and recognize glycolipids presented by CD1c on the surface of immature dendritic cells and can induce DC to mature and produce IL-12 [22], [23]. This population comprises cells that are highly cytotoxic to a wide variety of malignancies [24]–[29], and long-term persistence of Vδ1+ T cells in bone marrow transplant patients has been associated with long-term disease free survival [30], [31]. Vδ1-expressing T cells can also exhibit immunosuppressive and regulatory properties in addition to effector function [32], [33], a finding of particular importance in determining the interaction of γδ T cells and malignancy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vδ2(neg) γδ T cells, of which Vδ1+ γδ T cells are by far the largest subset, are important effectors against CMV infection. Malignant gliomas often contain CMV genetic material and proteins, and evidence exists that CMV infection may be associated with initiation and/or progression of glioblastoma multiforme (GBM). We sought to determine if Vδ1+ γδ T cells were cytotoxic to GBM and the extent to which their cytotoxicity was CMV dependent. We examined the cytotoxic effect of ex vivo expanded/activated Vδ1+ γδ T cells from healthy CMV seropositive and CMV seronegative donors on unmanipulated and CMV-infected established GBM cell lines and cell lines developed from short- term culture of primary tumors. Expanded/activated Vδ1+ T cells killed CMV-negative U251, U87, and U373 GBM cell lines and two primary tumor explants regardless of the serologic status of the donor. Experimental CMV infection did not increase Vδ1+ T cell - mediated cytotoxicity and in some cases the cell lines were more resistant to lysis when infected with CMV. Flow cytometry analysis of CMV-infected cell lines revealed down-regulation of the NKG2D ligands ULBP-2, and ULBP-3 as well as MICA/B in CMV-infected cells. These studies show that ex vivo expanded/activated Vδ1+ γδ T cells readily recognize and kill established GBM cell lines and primary tumor-derived GBM cells regardless of whether CMV infection is present, however, CMV may enhance the resistance GBM cell lines to innate recognition possibly contributing to the poor immunogenicity of GBM.
    PLoS ONE 08/2013; 8(8):e68729. DOI:10.1371/journal.pone.0068729 · 3.23 Impact Factor
Show more