scholarly journals Cytomegalovirus Infection in Pediatric Haploidentical Hematopoietic Stem Cell Transplantation at a Single Center

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2209-2209
Author(s):  
Sung Han Kang ◽  
Hyery Kim ◽  
Jong Jin Seo ◽  
Ho Joon Im ◽  
Eun Seok Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Ex Vivo ◽  
Clinical Aspects ◽  
Hematopoietic Stem ◽  
Group I ◽  
Pp65 Antigen ◽  
Cmv Disease ◽  
Cmv Prophylaxis ◽  
Cmv Reactivation

Abstract Introduction : Clinical aspects and risk factors of Cytomegalovirus (CMV) reactivation and diseases are an emerging interest in recent investigation fields of hematopoietic stem cell transplantation (HSCT). Several risk factors and clinical manifestations of CMV infection have been reported in numbers of previous reports. Monitoring of viral replication and timely given antiviral agents have resulted in a decreased incidence of CMV-related death recently. However, CMV in still a major cause of infectious complications after HSCT. Specially in haploidentical HSCT setting, clinical manifestations and associated risk factors have been rarely reported. This study is conducted to identify risk factors and clinical aspects of CMV reactivation and disease in pediatric haploidentical HSCT. Methods : We retrospectively reviewed the medical records of 92 pediatric patients who underwent haploidentical HSCT using ex vivo T cell-depleted grafts at Asan Medical Center between December, 2004 and June, 2016. After haploidentical HSCT, all recipients were monitored for CMV infection by CMV pp65 antigen and/or CMV-PCR. Both recipient and donor were screened for CMV serology before the HSCT. During the study period, methodologic changes in ex vivo T cell depletion and CMV prophylaxis policy have been modulated with the course of time. During the 1st study period (Group I, n=19), CD3+ T cell was depleted without CMV prophylaxis while ganciclovir for CMV prophylaxis was given with CD3+ T cell depletion during the 2nd period (Group II, n=16). The T cells expressing alpha-beta T cell receptor (TCRαβ) was depleted during the 3rd period (Group III, n=57) with ganciclovir prophylaxis. Results : Of the 92 patients, 49 (53.3%) developed CMV reactivation after haploidentical HSCT. CMV reactivation significantly reduced in group II and III compared to group I (84±8.4% vs 46±5.9%; p<0.001). Patients with chronic graft-versus-host-disease (GVHD) also experienced more reactivation (p=0.041). In the multivariate analysis, difference of study group was the only variable predicted the occurrence of CMV reactivation (Group I vs Group III; hazard ratio, 3.728; 95% confidence interval (CI), 1.910-7.278). CMV disease was developed in 16/92 (17.4%) patients during the study period (16/49, 32.7% among CMV reactivation patients). The peak CMV pp65 antigen level, peak CMV DNA-PCR level, and duration of CMV antigenemia were significantly higher in patients with CMV disease (p=0.024, p=0.009, p=0.046, respectively). In univariate analysis, the peak CMV pp65 antigen level (p=0.020), and duration of CMV antigenemia (p=0.05) were associated with increased occurrence of CMV disease. In multivariate analysis, CMV disease significantly increased in patients with high CMV pp65 antigenemia greater than 40/200,000 cells (hazard ratio, 3.568; 95% CI 1.062-12.594). CMV diseases included retinitis in 12 (75%), pneumonitis in 3 (25%), gastritis, colitis, and encephalitis in 1 (8.3%) each, respectively. Of the 16 patients, 3 patients (2 pneumonitis, 1 encephalitis) died of CMV disease. Conclusions : Our study demonstrated that ganciclovir prophylaxis has effectively reduced the occurrence of CMV reactivation in ex vivo T cell depleted haploidentical HSCT. In addition, close monitoring of CMV pp65 antigen and timely preemptive management is important to prevent CMV related death. Disclosures No relevant conflicts of interest to declare.

Reduced Non Relapse Mortality (NRM) and Survivable Acute Graft Versus Host Disease (GVHD) in the Current Era of Myeloablative Ex Vivo T-Cell Depleted (TCD) Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4596-4596
Author(s):  
Natasha A Jain ◽  
Prathima Anandi ◽  
Upneet Chawla ◽  
Sawa Ito ◽  
Debbie Draper ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Disease Risk ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
One Year ◽  
The Impact ◽  
Cmv Reactivation ◽  
Steroid Refractory

Abstract Introduction: Little is known about the lethality of acute GVHD (aGVHD) in T -cell depleted (TCD) allogeneic hematopoietic stem cell transplantation (HSCT). We examined the incidence of aGVHD and its relative contribution to non relapse mortality (NRM) in a cohort of consecutive TCD HSCT at a single institute. Methods: We report 132 consecutive subjects who had undergone TCD HLA-identical sibling HSCT between 2006 and 2016 for hematologic malignancies. All subjects received conditioning with Fludarabine 125mg/m2, Cytoxan 120 mg/kg and 1200 cGy total body irradiation (TBI) (<age 55 years) or 400-600 cGy (³age 55) followed by either a CD34+ selected (n=112) or CD3/19 depleted (n=20) peripheral blood stem cell graft with a T cell addback of 5-50x10e4CD3+/kg (Miltenyi CliniMACS, resulting in 3.5 to 4-log TCD). Low dose cyclosporine was used until day 21 for GVHD prophylaxis. Thirty-six subjects were over the age of 55 years, 66 were females and 66 were males. Transplant indications were acute leukemia (92), myelodysplastic / myeloproliferative syndromes (26), lymphoid malignancies (7) and chronic myelogenous or myelomonocytic leukemia (7). Fifty-three percent of subjects were at a high risk of relapse. The median follow-up post HSCT was 4.3 years. Results: The incidence of Grade 1-2 and 3-4 aGVHD were 51.6% and 19%, respectively. Of these, 15% of aGVHD was steroid refractory and was treated with infliximab/basiliximab or with mesenchymal stromal cells. Extensive or limited chronic GvHD was observed in 30% and 24% of subjects. 74% of those at risk developed cytomegalovirus (CMV) reactivation. The Kaplan-Meier (KM) estimate for overall survival (OS), NRM and cumulative incidence of relapse (CIR) for the entire cohort was 71%, 14.6% and 24% respectively at one year, and 52%, 32.5% and 39% at 5 years. We considered the impact of CMV reactivation, slow donor lymphoid chimerism and steroid refractory aGVHD on NRM. However there was no significant impact from CMV reactivation or slow (> 31 days) achievement of complete donor lymphoid chimerism. Significantly improved outcomes were noted for those transplanted beyond 2012: OS, NRM and CIR being 82%,6.2% and 20% at one year, and 68%, 6.2% and 41% at 3 years. Cox proportionate hazard modeling identified steroid refractory aGVHD (HR 4.0, P=0.007) and transplant prior to 2012 (HR 6.7, P=0.001) as significant factors impacting NRM. Conclusions: T cell addback after ex vivo TCD HSCT was associated with a significant burden of aGVHD. Steroid refractory aGVHD impacted NRM, but slow lymphoid engraftment, disease risk, CMV reactivation and age did not. Significant improvements in NRM in the current era suggest greatly improved salvage of steroid refractory aGVHD. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Heterogeneous impact of cytomegalovirus reactivation on nonrelapse mortality in hematopoietic stem cell transplantation

2020 ◽  
Vol 4 (6) ◽  
pp. 1051-1061 ◽  
Author(s):  
Satoshi Kaito ◽  
Yujiro Nakajima ◽  
Konan Hara ◽  
Takashi Toya ◽  
Tetsuya Nishida ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Large Scale ◽  
Performance Status ◽  
Major Complication ◽  
Hematopoietic Stem ◽  
Cmv Prophylaxis ◽  
Cmv Reactivation

Abstract Cytomegalovirus (CMV) infection is a major complication in allogeneic stem cell transplantation. The utility of CMV prophylaxis with letermovir has been reported; however, the specific applications remain unclear. In this study, we retrospectively analyzed large-scale registry data (N = 10 480) to clarify the risk factors for nonrelapse mortality (NRM) in connection with CMV reactivation. First, we identified risk factors for CMV reactivation using multivariate analysis and developed a scoring model. Although the model effectively stratified reactivation risk into 3 groups (43.7% vs 60.9% vs 71.5%; P &lt; .001), the 3-year NRM was significantly higher in patients with CMV reactivation, even in the low (20.9% vs 13.0%, P &lt; .001), intermediate (21.4% vs 15.6%; P &lt; .001), and high (29.3% vs 18.0%; P &lt; .001) reactivation risk groups. Next, survival analysis considering competing risks, time-dependent covariates, and interaction terms for exploring the heterogeneous impact of CMV reactivation on NRM in the training cohort revealed that chronic myeloid leukemia (CML) (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.05-2.96; P = .033), good performance status (PS) (HR, 1.42; 95% CI, 1.04-1.94; P = .028), HLA-matched donor (HR, 1.34; 95% CI, 1.06-1.70; P = .013), and standard-risk disease (HR, 1.28; 95% CI, 1.04-1.58; P = .022) were associated with increased NRM. In the test cohort, CMV reactivation was significantly associated with increased 3-year NRM among patients with 2 to 4 factors (22.1% vs 13.1%; P &lt; .001) but was comparable among patients with 0 or 1 factor (23.2% vs 20.4%; P = .62). We propose that CMV prophylaxis should be determined based on reactivation risk, as well as these other factors.

scholarly journals How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2020 ◽  
Vol 135 (19) ◽  
pp. 1619-1629 ◽  
Author(s):  
Hermann Einsele ◽  
Per Ljungman ◽  
Michael Boeckh
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract Cytomegalovirus (CMV) reactivation remains one of the most common and life-threatening infectious complications following allogeneic hematopoietic stem cell transplantation, despite novel diagnostic technologies, several novel prophylactic agents, and further improvements in preemptive therapy and treatment of established CMV disease. Treatment decisions for CMV reactivation are becoming increasingly difficult and must take into account whether the patient has received antiviral prophylaxis, the patient’s individual risk profile for CMV disease, CMV-specific T-cell reconstitution, CMV viral load, and the potential drug resistance detected at the time of initiation of antiviral therapy. Thus, we increasingly use personalized treatment strategies for the recipient of an allograft with CMV reactivation based on prior use of anti-CMV prophylaxis, viral load, the assessment of CMV-specific T-cell immunity, and the molecular assessment of resistance to antiviral drugs.

scholarly journals Systemic T Cell–independent Tumor Immunity after Transplantation of Universal Receptor–modified Bone Marrow into SCID Mice

1996 ◽  
Vol 184 (6) ◽  
pp. 2261-2270 ◽  
Author(s):  
Kristen M. Hege ◽  
Keegan S. Cooke ◽  
Mitchell H. Finer ◽  
Krisztina M. Zsebo ◽  
Margo R. Roberts
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Lethal Dose ◽  
Cell Receptor ◽  
Scid Mice ◽  
Human Leukemia ◽  
Hematopoietic Stem ◽  
Retroviral Transduction ◽  
Hiv Envelope

Gene modification of hematopoietic stem cells (HSC) with antigen-specific, chimeric, or “universal” immune receptors (URs) is a novel but untested form of targeted immunotherapy. A human immunodeficiency virus (HIV) envelope–specific UR consisting of the extracellular domain of human CD4 linked to the ζ chain of the T cell receptor (CD4ζ) was introduced ex vivo into murine HSC by retroviral transduction. After transplantation into immunodeficient SCID mice, sustained high level expression of CD4ζ was observed in circulating myeloid and natural killer cells. CD4ζ-transplanted mice were protected from challenge with a lethal dose of a disseminated human leukemia expressing HIV envelope. These results demonstrate the ability of chimeric receptors bearing ζ-signaling domains to activate non–T cell effector populations in vivo and thereby mediate systemic immunity.

Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4358-4366 ◽  
Author(s):  
Kieren A. Marr ◽  
Rachel A. Carter ◽  
Michael Boeckh ◽  
Paul Martin ◽  
Lawrence Corey
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Invasive Aspergillosis ◽  
Respiratory Virus ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Cmv Disease

The incidence of postengraftment invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients increased during the 1990s. We determined risks for IA and outcomes among 1682 patients who received HSCTs between January 1993 and December 1998. Risk factors included host variables (age, underlying disease), transplant variables (stem cell source), and late complications (acute and chronic graft-versus-host disease [GVHD], receipt of corticosteroids, secondary neutropenia, cytomegalovirus [CMV] disease, and respiratory virus infection). We identified risk factors associated with IA early after transplantation (≤ 40 days) and after engraftment (41-180 days). Older patient age was associated with an increased risk during both periods. Chronic myelogenous leukemia (CML) in chronic phase was associated with low risk for early IA compared with other hematologic malignancies, aplastic anemia, and myelodysplastic syndrome. Multiple myeloma was associated with an increased risk for postengraftment IA. Use of human leukocyte antigen (HLA)–matched related (MR) peripheral blood stem cells conferred protection against early IA compared with use of MR bone marrow, but use of cord blood increased the risk of IA early after transplantation. Factors that increased risks for IA after engraftment included receipt of T cell–depleted or CD34-selected stem cell products, receipt of corticosteroids, neutropenia, lymphopenia, GVHD, CMV disease, and respiratory virus infections. Very late IA (> 6 months after transplantation) was associated with chronic GVHD and CMV disease. These results emphasize the postengraftment timing of IA; risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.

scholarly journals Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplant Recipients in High Endemic Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Muhammad Farhan ◽  
Qamar Un Nisa Chaudhry ◽  
Syed Kamran Mahmood ◽  
Tariq Ghafoor ◽  
Raheel Iftikhar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Viral Load ◽  
High Viral Load ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Endemic Population ◽  
Cmv Reactivation

Background: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). It causes end-organ disease, multi-organ dysfunction syndrome, graft failure, increased susceptibility to infections and GVHD. According to the published western data greatest risk of CMV infection is the seropositivity of the recipient, however, in a high endemic population where seropositivity is up to 100%, risk factors for CMV reactivation are different and are analyzed in this study. Methods: It is a prospective descriptive study performed at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan from January 2017 to March 2020. Consecutive patients who underwent allogeneic HSCT during this period were enrolled. All patients were prospectively monitored for CMV reactivation by weekly or two weekly CMV DNA quantitative PCR, from engraftment till day 100 post-transplant. CMV infection was diagnosed on detection of more than 200 copies/ml on PCR. Threshold for starting preemptive antiviral therapy was kept at 2000 copies/ml. Patients with past history of CMV infection, those who expired before day 14 post-transplant or those with less than 70% of required CMV tests were not included in the study. Factors associated with CMV reactivation, outcome of antiviral therapy and effect of CMV on post-transplant survival were studied. Results: Out of 319 transplants during this period, 230 patients fulfilled the inclusion criteria. Of these, 197 were HLA matched sibling, 18 were matched family donor and 15 were haploidentical transplants. There were 163 males and 67 females. Median age at transplant was 9.5 years (0.5-53). Eighty-three transplants were done in thalassemia, 55 in aplastic anemia, 14 in Fanconi anemia, 27 in acute leukemias, 8 in CML, 9 in MDS, 12 in HLH and 22 in other hematological disorders. All the patients and donor were CMV IgG seropositive when tested before transplantation. CMV reactivation was seen in 152 out of 230 patients (66.1%). Of 152, 95 patients had CMV viral load more than 2000 copies/ml and required antiviral treatment. Median time to reactivation since transplant was 35 days (13-90). In multivariate analysis using binary regression, risk factors for high viral load CMV reactivation included steroid administration (p=0.009), recipient age less than 10 years (p=0.003) and haploidentical transplant (p=0.048). No statistically significant association was found with the use of ATG, GVHD, underlying disease, ABO blood group or gender mismatch. Survival analysis using cox regression showed significant impact of high viral load CMV reactivation on post-transplant survival. Event-free survival (EFS) with and without CMV reactivation was 70.5 % and 89.7% respectively (p=0.004) and overall survival (OS) was 80.0 % and 97.4 % with and without CMV reactivation respectively (p=0.002). Valganciclovir was given in 89 patients and 6patients were treated with ganciclovir. Mean time to clear viremia was 19.8±9 days. Myelosuppression was seen in 41% of patients treated with valganciclovir. Renal impairment was seen in 25% of patients treated with valganciclovir. One patient had resistant disease. One patient had CMV pneumonia and she recovered. One patient died of suspected CMV pneumonia Conclusion: CMV reactivation was seen in 66.1% of the transplant recipients, this is higher compared to the western world due to high CMV seropositivity is this region. Steroids administration in post-transplant period significantly increase the risk of CMV reactivation. Preemptive therapy with valganciclovir effectively treats CMV reactivation. Viral threshold for treatment should be decided considering the regional endemicity. CMV adversely effects the transplant outcome in terms of EFS and OS. Disclosures No relevant conflicts of interest to declare.

P1667ANALYSIS OF RISK FACTORS FOR CMV DISEASE IN KIDNEY TRANSPLANT PATIENTS - SINGLE CENTER STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Vladimir Hanzal ◽  
Janka Slatinska ◽  
Petra Hruba ◽  
Ondrej Viklicky
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Kidney Graft ◽  
Cmv Infection ◽  
Post Transplantation ◽  
Increased Risk ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Abstract Background and Aims Cytomegalovirus (CMV) disease and infection negatively influence outcome of kidney transplantation. The aim of this retrospective study was to analyze risk factors for CMV disease and its influence on kidney graft function and survival. Method 1050 patients underwent kidney transplantation from January 2014 to December 2018 and received calcineurin inhibitor, mycophenolate mofetil and steroid-based immunosuppression. Recipients with PRA&gt;20% received rATG while others had received basiliximab as induction. 825 out of 1050 patients (78.6%) received CMV prophylaxis (D+/R-, n=173; R+, n=652). Patients were followed up to 71 months /median 38 months/. Results CMV tissue invasive disease occurred in 49 out of 1050 patients (4.7%), while CMV infection in 87 patients (8.3%). CMV disease, but not CMV infection, had significant negative influence on graft survival at 5 years post transplantation (p=0.0029). Patients with CMV disease had significantly worse graft function at 4 years post transplantation (p&lt;0.0001). CMV disease occurred in 31 out of 173 patients (17.9%) in D+/R- group vs. 18 out of 652 patients (2.8%) in R+ group. Incidence of CMV infection was 30/173 patients (17.3%) in D+/R- group vs. 57/652 patients (8.7%) with induction therapy. Shortening of CMV prophylaxis was found in 82 patients (9.9%). Leukopenia (≤ 2.0 x 109/L) was observed in 97 (11.7%) patients from those who received CMV prophylaxis, Its shortening significantly increased risk for both CMV infection (20,7% vs. 7.2%, p&lt;0,0001) and CMV disease (8,5% vs. 4,2%, p=0,04). Among most significant risk factors for CMV disease in univariable analysis were CMV mismatch (OR 11, 95% CI: 5,9-20,4; p&lt;0,0001), delayed graft function (OR 2,8, 95% CI: 1,6-5,1; p&lt;0,0001, cadaveric donor (OR 6, 95% CI: 1,5-25,1; p=0,00013) and shortening of CMV prophylaxis (OR 2.1, 95% CI: 0,91-4,86; p=0,08). Multivariable analysis revealed as independent significant predictors of CMV disease DGF (OR 2,29, 95% CI: 1,2-4,3; p=0,01) and CMV mismatch (OR 10,8, 95% CI: 5,7-20,6; p&lt;0.0001) in a model adjusted for type of donor, prophylaxis shortening and leukopenia. Conclusion CMV mismatch is the main independent predictor of CMV disease after kidney transplantation in multivariable analysis.

Evaluation of Cytomegalovirus (CMV)-Specific Cytotoxic T Lymphocyte (CTL) Monitoring Procedures with Tetramer and Intracellular IFN-γ Assay after Allogeneic Hematopoietic Stem Cell Transplantation (SCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3161-3161
Author(s):  
Yuriko Morita ◽  
Mami Hosokawa ◽  
Yuji Heike ◽  
Tohru Sasaki ◽  
Michiko Ebisawa ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Disease Onset ◽  
Hematopoietic Stem ◽  
Ifn Γ ◽  
Cmv Colitis ◽  
Cmv Disease ◽  
Cmv Reactivation ◽  
Matched Donor ◽  
Cmv Antigenemia

Abstract Previous studies on the tetramer-based quantification of CMV-specific CTL have shown that the reconstitution of CMV-specific CTL to levels greater than 10/μL may protect against CMV reactivation. To evaluate the usefulness of CMV-specific tetramer for monitoring the number of CMV-specific CTL, assays with CMVpp65 495–503 tetramer were performed in 34 patients with HLA-A02 while CMVpp65 328–336 tetramer was used in 47 HLA-A24 patients who received non-T-cell-depleted SCT from a serologically full-matched donor after a myeloablative or nonmyeloablative regimen without ATG. Patients were assessed after recovery from CMV reactivation. Although the average number of CTL detected in patients with HLA-A02 [23.5/μL (1.33%/lymphocytes)] was significantly higher than that in patients with HLA-A24 [0.48/μL (0.02%)], the CMV reactivation rate was similar (67.6% and 62.5% in HLA-A02 and A24, respectively). This result demonstrates that these assays are of limited value since the number of CTL detected varies among different HLA-restricted epitopes. To further evaluate whether there is any relationship between CMV-specific CTL and CMV reactivation, the number of CTL in HLA-A02 patients was assessed in detail. The average number of CTLs in 11 patients without CMV reactivation, 23 with CMV reactivation, 13 with a peak CMV antigenemia of &gt;10/50000, and 3 who developed CMV disease was 12.3/μL (0.85%), 29.3/μL (1.35%), 13.8/μL (0.8%) and 16.3/μL (1.33%), respectively. No significant correlation was observed between the number of CTL and CMV reactivation after the reconstitution of CMV immunity. Since CMV reactivation usually occurs within 100 days after SCT, tetramer was assessed biweekly until day 100 in 13 HLA-A02 patients. In those who had CMV reactivation, simultaneous intracellular IFN-γ staining was performed with the same peptide used for tetramer. CMV reactivation was observed in 10 patients between day 23 and day 56 (median, day 34); among them, 5 had a peak antigenemia of &gt;10/50000, and required GCV therapy, and 3 developed CMV colitis. The average number of CTL at CMV reactivation was 5.67 (0.08–22.65) /μL in 10 patients who had reactivation, with 3 showing &gt;10/μL, while this was 1.08 (0–1.98) /μL at day 30 in those who did not. Two of the 3 patients who developed CMV colitis had &gt;10/μL CTL at the time of disease onset, while among 8 who did not require GCV therapy, only 1 and 2 patients recovered CTL &gt;10/μL at day 30 and day 60, respectively. The number of intracellular IFN-γ-secreting cells among those with CMV colitis was 18.2/μL (1.8%) at the time of disease onset, and this increased to 47.3/μL (3.5%) after recovery from CMV disease. These results suggest that tetramer-based monitoring of CTL is of limited value in predicting CMV reactivation compared to intracellular IFN-γ assay that assesses the functional properties of CTL.

Sign in / Sign up

Export Citation Format

Share Document