scholarly journals Performance of the QuantiFERON-Cytomegalovirus (CMV) Assay for Detection and Estimation of the Magnitude and Functionality of the CMV-Specific Gamma Interferon-Producing CD8+T-Cell Response in Allogeneic Stem Cell Transplant Recipients

2012 ◽  
Vol 19 (5) ◽  
pp. 791-796 ◽  
Author(s):  
María Ángeles Clari ◽  
Beatriz Muñoz-Cobo ◽  
Carlos Solano ◽  
Isabel Benet ◽  
Elisa Costa ◽  
...  

ABSTRACTThe performance of the QuantiFERON-cytomegalovirus (CMV) assay was compared to that of a flow cytometry intracellular cytokine staining (ICS) method for the detection of CMV-specific gamma interferon (IFN-γ)-producing CD8+T-cell responses in allogeneic stem cell transplant (allo-SCT) recipients and for estimations of their magnitude and functionality. A total of 90 whole-blood specimens from 23 allo-SCT recipients was analyzed by both methods. Overall, the percentage of specimens that yielded concordant results by both methods was 68.8% (κ = 0.691; 95% confidence interval [CI], 0.548 to 0.835), and the sensitivity of the QuantiFERON-CMV assay for the detection of positive IFN-γ T-cell responses (>0.2 IU/ml), taking the ICS method as the reference, was 76.3%. The magnitude of IFN-γ-producing CD8+T-cell responses to CMV-specific peptides measured with the QuantiFERON-CMV assay correlated significantly (σ = 0.695;P= <0.001) with that of the total IFN-γ-producing CD8+T cells and dual-functional (IFN-γ/tumor necrosis factor alpha [TNF-α] [σ = 0.652;P= <0.001] and IFN-γ/CD107a [σ = 0.690;P= <0.001]) and trifunctional (IFN-γ/TNF-α/CD107a [σ = 0.679;P= >0.001]) CMV-specific CD8+T-cell responses, as quantitated by ICS. In summary, the data indicated that the QuantiFERON-CMV assay is less sensitive than the ICS method for the detection of CMV-specific IFN-γ-producing CD8+T-cell responses in the allo-SCT setting. Nevertheless, it allowed the estimation of the total and polyfunctional CMV-specific IFN-γ-producing CD8+T-cell responses in specimens that tested positive by both methods.

2010 ◽  
Vol 51 (6) ◽  
pp. 1055-1062 ◽  
Author(s):  
Dominik Schneidawind ◽  
Anita Schmitt ◽  
Markus Wiesneth ◽  
Thomas Mertens ◽  
Donald Bunjes ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 504-504
Author(s):  
Patrick Hanley ◽  
Barbara Savoldo ◽  
Conrad Russell Young Cruz ◽  
Ann M. Leen ◽  
Jeffrey J. Molldrem ◽  
...  

Abstract Abstract 504 Allogeneic stem cell transplantation is the treatment of choice for patients with high-risk hematologic malignancies. Umbilical cord blood (CB) has emerged as an important source of stem cells for allotransplant patients lacking human leukocyte antigen (HLA)-matched donors–a significant problem for minorities. T cells in UCB grafts are, however, virus-naïve, leading to higher mortality rates due to infections with CMV, EBV, adenovirus (Ad) and other viruses. Peripheral Blood Stem Cell Transplant (PBSCT) from CMV-seronegative (CMVneg) donors to CMV-seropositive (CMVpos) recipients produces a similarly high incidence of CMV infection since donor T cells are naïve to this virus. Adoptive immunotherapy with peripheral blood (PB)-derived CMV/Ad-specific CTL generated from CMVpos donors effectively prevents CMV clinical disease after PBSCT, but this option has not been feasible when the donor cells are naive, irrespective of whether they are sourced from CB or CMV-PBS, since CTL generation from these donors has been unsuccessful. We have now overcome this problem and can routinely generate CMV, Ad and EBV-specific CTLs from CB and CMV specific CTLs from seronegative PBSC. We used an Ad5f35vector carrying the CMVpp65 transgene to transduce CB-derived or PB-derived dendritic cells and stimulate virus-specific CTL in the presence of IL-7, IL-12 and IL-15. This was followed by 2 stimulations with autologous EBV-lymphoblastoid cell lines (LCL) transduced with the same vector. The 9 CB-derived CTL lines we made in this way contained a mean of 87% (range 81-94) CD8+ and 26% (range 12-40) CD4+T cells, and exhibited significant cytotoxicity in 51Cr release assays against CMVpp65, Adhexon, and LCL targets. In IFN-γ ELISPOT assays there was a mean of 209 (range 45-694), 74 (range 0-128), and 157 (range 23-291) SFC following incubation with CMVpp65, Adhexon peptides and LCL, respectively. In addition, we generated CMVpp65, Adhexon, and LCL-specific responses from the peripheral blood of 4 CMVneg adult donors, which produced a mean of 92 (range 50-126), 163 (range 69-293), and 62 (range 37-86) SFC to CMVpp65 respectively. Neither CB- nor CMVneg-derived CTL responded to irrelevant peptides. Of note, the virus-specific T cells that we expanded from both CB and CMVneg donors derived only from T cells with a naive phenotype (CD45RA+/CCR7+). Moreover, both CB and CMVneg-derived CTL recognized ‘unconventional‘ CMV pp65 epitopes, as identified by overlapping pp65 peptide pools and confirmed by IFN-γ ELISPOT as well as multimer analysis (Table 1). In HLA-A2+ subjects, these naive-derived CTLs did not recognize conventional HLA-A2-associated CMV pp65 epitopes such as NLV, suggesting an inherent difference between naïve and memory T cell responses to CMV. In summary, virus-specific responses T cell responses can be obtained even from CB and virus-naive adult donors and may allow prevention and treatment of viral disease in the recipients of these allografts. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 51 (12) ◽  
pp. 1549-1555 ◽  
Author(s):  
E H Phillips ◽  
A Hodson ◽  
O Hermine ◽  
A Bazarbachi ◽  
K Cwynarski

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Parikshit Padhi ◽  
Margarita Topalovski ◽  
Radwa El Behery ◽  
Eduardo S. Cantu ◽  
Ramadevi Medavarapu

Chronic Myelogenous Leukemia in blast crisis can manifest as either myeloid (more common) or lymphoid blast crisis. Most lymphoblastic crises are of B-cell lineage. T-cell blast crisis is extremely rare, with only a few reported cases. We present a case of a middle-aged man who was diagnosed with CML on peripheral blood and bone marrow biopsy. Because of a generalized lymphadenopathy noted at the time of diagnosis, a lymph node biopsy was also performed, which revealed a T-cell lymphoblastic leukemia/lymphoma, BCR/ABL1 positive, with clonal evolution. This is a very rare manifestation of CML in blast crisis with no standard treatment and with poor outcomes despite chemotherapy or allogeneic stem cell transplant. Given its rarity, it would be difficult to develop standard chemotherapy protocols. We believe the treatment for this condition should be similar to any lymphoid blast crisis. The patient was treated with induction chemotherapy (hyper-CVAD regimen) plus dasatinib for 3 cycles followed by sibling-donor allogeneic stem cell transplant and is currently on maintenance dasatinib and has minimal residual disease at this time.


2021 ◽  
Vol 27 (3) ◽  
pp. S421-S422
Author(s):  
Edward Robert Scheffer Cliff ◽  
Thomas Eliot Lew ◽  
Piers Blombery ◽  
Michael Dickinson ◽  
Constantine S. Tam ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document