Prospective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1406-1412 ◽  
Author(s):  
Daniele Lilleri ◽  
Giuseppe Gerna ◽  
Chiara Fornara ◽  
Laura Lozza ◽  
Rita Maccario ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell ◽  
Human Cytomegalovirus ◽  
Immune Reconstitution ◽  
Hcmv Infection ◽  
Cd8 T Cell ◽  
Cell Transplant ◽  
Hematopoietic Stem

AbstractWe investigated immune reconstitution against human cytomegalovirus (HCMV) in 57 hematopoietic stem cell transplant (HSCT) recipients, aged 1 to 24 years, through a novel method combining T-cell stimulation by HCMV-infected autologous dendritic cells with simultaneous cytometric quantification of HCMV-specific, IFNγ-producing CD4+ and CD8+ T cells. Lymphoproliferative response (LPR) to HCMV antigens was also determined. Patients were stratified into 2 groups according to HCMV serostatus, comprising 39 HCMV-seropositive (R+) and 18 HCMV-seronegative (R–) patients who received a transplant from a sero-positive donor. Recovery of both HCMV-specific CD4+ and CD8+ T-cell immunity occurred in all 39 R+ patients within 6 months and in 6 (33%) of 18 R– patients within 12 months. In R+ patients, the median numbers of HCMV-specific CD8+ and CD4+T cells were significantly higher than those of healthy controls, starting from days +60 and +180, respectively. In R– patients, the median numbers of HCMV-specific T cells were consistently lower than in R+ patients. LPR was delayed compared with reconstitution of IFNγ-producing T cells. Patients with delayed specific immune reconstitution experienced recurrent episodes of HCMV infection. HCMV seropositivity of young HSCT recipients is the major factor responsible for HCMV-specific immune reconstitution, irrespective of donor serostatus, and measurement of HCMV-specific T cells appears useful for correct management of HCMV infection.

Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 5053-5060 ◽  
Author(s):  
Giuseppe Gerna ◽  
Daniele Lilleri ◽  
Fausto Baldanti ◽  
Maria Torsellini ◽  
Giovanna Giorgiani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Immediate Early ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Hcmv Disease ◽  
Significant Difference

AbstractIn the search for better protocols of preemptive therapy of human cytomegalovirus (HCMV) infection in hematopoietic stem cell transplant (HSCT) recipients, we conducted a randomized trial comparing antigenemia with the nucleic acid sequence–based assay (NASBA) for determination of HCMV immediate-early messenger RNA (IEmRNA) as the guiding assay for initiation of pre-emptive antiviral treatment. In the IEmRNA arm, antiviral therapy was started upon IEmRNA positivity confirmed the following day, whereas in the antigenemia arm, therapy was started in the presence of either at least 2 pp65-positive leukocytes/2 × 105 examined or a single positive leukocyte confirmed the following day. In both arms, treatment was stopped upon 2 consecutive negative results. All patients were monitored for 3 months after HSCT. The primary end point of the study was duration of anti-HCMV therapy. On the whole, 80 children (41 in the IEmRNA and 39 in the antigenemia arm), recipients of transplants from either a relative or an unrelated donor, completed the study. No patient developed HCMV disease. In the IEmRNA arm, the incidence of HCMV infection was higher compared to the antigenemia arm (80% vs 51%, respectively, P = .0069), as well as the percentage of treated patients (66% vs 44%, respectively, P = .045). However, the percentage of relapses and treated relapses was comparable in the 2 arms. There was no significant difference in median duration of therapy per patient. Although these data indicate that IEmRNA determination does not offer advantages in terms of treatment duration, it can safely replace antigenemia, while semiautomation is the major advantage of the NASBA procedure.

Relapsed subcutaneous panniculitis-like T cell lymphoma: role of haploidentical hematopoietic stem cell transplant

2017 ◽  
Vol 96 (12) ◽  
pp. 2125-2126 ◽  
Author(s):  
Bhagirathbhai Dholaria ◽  
Raj J. Patel ◽  
Jason C. Sluzevich ◽  
Sikander Ailawadhi ◽  
Vivek Roy
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Hematopoietic Stem

scholarly journals Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lorenzo Canti ◽  
Stéphanie Humblet-Baron ◽  
Isabelle Desombere ◽  
Julika Neumann ◽  
Pieter Pannus ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Chronic Gvhd ◽  
Neutralizing Antibody ◽  
Healthy Adults ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Factors Affecting

Abstract Background Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. Methods Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses. Results Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01). Conclusions Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination. Trial registration The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).

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