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

Hoegh-Petersen, Mette; Sy, Sarah; Ugarte-Torres, Alejandra; Williamson, Tyler; Eliasziw, Michael; Mansoor, Adnan; Liu, Y; Liu, S; Podgorny, Peter; Khan, Faisal; Duggan, Peter; Stewart, Douglas A.; Russell, James A.; Storek, Jan

doi:10.1038/leu.2011.195

Cited by 15 publications

(8 citation statements)

References 8 publications

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“…A lower leukemia relapse risk in the presence of herpes virus-specific T cells provided a first direct correlation between virus-and alloreactive T cell responses in pediatric patients after umbilical cord blood transplantation [51]. The latter observation was confirmed by a later report showing that T cell responses against herpes viruses are associated with the absence of leukemia relapse in highrisk acute myeloid leukemia patients [52].…”

Section: Discussionmentioning

confidence: 84%

Possible Impact of Cytomegalovirus-Specific CD8+ T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell Transplantation

Ogonek

Varanasi

Luther

et al. 2017

Biology of Blood and Marrow Transplantation

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Complete donor chimerism is strongly associated with complete remission after allogeneic stem cell transplantation (allo-SCT) in patients with hematologic malignancies. Donor-derived allo-immune responses eliminate the residual host hematopoiesis and thereby mediate the conversion to complete donor chimerism. Recently, cytomegalovirus (CMV) reactivation was described to enhance overall T cell reconstitution, to increase graft-versus-host disease incidence, and to reduce the leukemia relapse risk. However, the link between CMV and allo-immune responses is still unclear. Here, we studied the relationship between CMV-specific immunity, overall T cell reconstitution, and residual host chimerism in 106 CMV-seropositive patients transplanted after reduced-intensity conditioning including antithymocyte globulin. In accordance with previous reports, the recovery of CMV-specific cytotoxic T cells (CMV-CTLs) was more frequent in CMV-seropositive recipients (R) transplanted from CMV-seropositive than from seronegative donors (D). However, once CMV-CTLs were detectable, the reconstitution of CMV-specific CTLs was comparable in CMV R+/D- and R+/D+ patients. CD3 and CD8 T cell reconstitution was significantly faster in patients with CMV-CTLs than in patients without CMV-CTLs both in the CMV R+/D- and R+/D+ setting. Moreover, CMV-CTL numbers correlated with CD3 and CD8 T cell numbers in both settings. Finally, presence of CMV-CTLs was associated with low host chimerism levels 3 months after allo-SCT. In conclusion, our data provide a first indication that CMV-CTLs in CMV-seropositive patients might trigger the reconstitution of T cells and allo-immune responses reflected by the conversion to complete donor chimerism.

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Section: Discussionmentioning

confidence: 84%

Possible Impact of Cytomegalovirus-Specific CD8+ T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell Transplantation

Ogonek

Varanasi

Luther

et al. 2017

Biology of Blood and Marrow Transplantation

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“…This would be anticipated since many relapsed CML patients were successfully salvaged by tyrosine kinase inhibitors and/or donor lymphocyte infusions. 13, 15 The quality of the immune response to CMV or EBV has been previously shown to serve as a surrogate for donor T cell mediated anti-leukemia effects 16–18 . Thomson et al recently reported no significant association of AML relapse and CMV reactivation in alemtuzumab-based T-deplete allo-SCT.…”

Section: Discussionmentioning

confidence: 99%

CMV reactivation is associated with a lower incidence of relapse after allo-SCT for CML

Ito

Pophali

et al. 2013

Bone Marrow Transplant

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Preemptive therapy at CMV reactivation has diminished post-transplant CMV mortality. Furthermore, recent studies suggest a favorable “virus-versus-leukemia” effect from reactivating CMV, reducing relapse of acute myeloid leukemia (AML) after SCT. We studied the relationship of CMV reactivation with leukemic relapse in 110 patients with chronic myeloid leukemia (CML) receiving HLA-identical sibling SCT between 1993 and 2008. Seventy nine (71.8%) were in chronic phase, 5 in second chronic phase, 17 in accelerated phase and 9 in blast phase. Ninety seven patients (88.2%) received a myeloablative conditioning regimen; 99 received 4-log ex vivo T-cell depleted grafts and 13 received T-replete grafts. CMV reactivation before day 100 was observed in 72 patients (65.5%). At a median follow up of 6.2 years, CMV reactivation

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“…The strategy of quantifying EBV‐specific CD8 + T lymphocytes in monitoring the development of EBVD has also been examined. Unfortunately, the value of virus‐specific T cells as an immune biomarker to predict the risk and the severity of opportunistic infections after HSCT is still controversial . This is mostly because different methods for measurement have been used among studies (e.g., MHC‐peptide tetramers, intracellular cytokine staining, or ELISPOT assays), as well as different protocols.…”

Section: Discussionmentioning

confidence: 99%

Late‐onset Epstein–Barr virus‐related disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation is associated with impaired early recovery of T and B lymphocytes

Liu

Yan

Zhang

et al. 2015

Clinical Transplantation

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Epstein-Barr virus-related disease (EBVD) is a serious clinical complication in patients who have undergone haploidentical hematopoietic stem cell transplantation (haploHSCT). Some recipients develop EBVD relatively late after haploHSCT, and most of these patients suffer a poor outcome. This retrospective cohort study characterized the early adaptive immune recovery of patients with acute leukemia presenting with EBVD more than 100 d after haploHSCT. Patients with acute leukemia who received haploHSCT and developed EBVD 100 d later (n = 8) were compared with a matched control group without EBVD (n = 24) with regard to peripheral WBC, lymphocytes, and neutrophils (at 30, 60, and 90 d) and recoveries of B and T lymphocytes (at 30 and 90 d, via immunophenotyping/flow cytometry). Ninety days after haploHSCT, the median values of WBCs and lymphocytes, and the recoveries of CD19(+) B cells and CD4(+) , CD8(+) , and CD4(+) CD45RO(+) T cells, were significantly lower in patients who developed EBVD, relative to the control group. These results suggest a significant association between deficient early recovery of B and T lymphocytes and the development of late-onset EBVD after haploHSCT. Our observation could facilitate clinical intervention and the improvement of overall survival of patients undergoing haploHSCT.

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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

Cited by 15 publications

References 8 publications

Possible Impact of Cytomegalovirus-Specific CD8+ T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell Transplantation

Possible Impact of Cytomegalovirus-Specific CD8+ T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell Transplantation

CMV reactivation is associated with a lower incidence of relapse after allo-SCT for CML

Late‐onset Epstein–Barr virus‐related disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation is associated with impaired early recovery of T and B lymphocytes

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