Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion

Abstract

We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4(+) and CD8(+) T cell reconstitution, whereas ATG only delayed CD4(+) T cell reconstitution. Considering the reconstitution kinetics of CD4(+) and CD8(+) T cells, CMV-specific CD8(+) T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (< or =161 versus >161/microl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8(+) T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4(+)/CD8(+) T cell reconstitution kinetics in patients after allo-SCT.

Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT

“…1 Alemtuzumab and ATG differentially influence CD4+/8+ T-cell reconstitution kinetics post allo-HSCT, with alemtuzumab affecting both CD4/8-expressing cells and ATG only CD4. 54 Our homogeneous, alemtuzumab-conditioned cohort (in which no patient received ATG) found no effect of ABO mismatch on transplant outcomes, but there are limited data for ATG conditioning. Blin et al 28 investigated the effect of ABO mismatch in a matched unrelated donor cohort undergoing allogeneic HSCT.…”

The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT

“…Thus, alemtuzumab represents an important risk factor for CMV reactivation in patients receiving haploidentical HSCT, which has been observed in other patients with or without allogeneic HSCT. 30,35,36 In conclusion, TCD by graft engineering or alemtuzumab seem to be equally effective for haploidentical HSCT. This is reassuring as it offers the possibility that transplant centers can choose the TCD according the equipment and local feasibility.…”

Viral encephalitis after allogeneic stem cell transplantation: a rare complication with distinct characteristics of different causative agents

“…CMV infection) has been attributed particularly to alemtuzumab and might be due to long-term suppression of both CD4 + and CD8 + T cells by this agent. 21,22 Viral encephalitis was mainly caused by HHV-6, followed by EBV, HSV, JC virus, CMV, VZV and adenovirus. Thus the spectrum of causative viruses associated with encephalitis after allo-SCT differs markedly from that seen in non-immunocompromised hosts (mainly HSV and VZV) and also from that found in other immunosuppressive conditions like acquired immunodeficiency syndrome, where several groups reported a preponderance of CMV, followed by PML, EBV, VZV, HSV and finally HHV-6.…”

“…2,15,20 In vivo T-cell depletion (particularly with alemtuzumab), graft-versus-host disease (GvHD) prophylaxis with mycophenolate mofetil and fludarabine-based conditioning prior to allo-SCT have previously been implicated in the development of systemic viral infections such as CMV antigenemia, but the impact of these variables on the occurrence of viral encephalitis has not yet been evaluated in a larger cohort. 21,22 In this study, 2,628 patients who underwent allo-SCT in 11 transplant units in Germany were screened for viral encephalitis on the basis of a positive CSF PCR in combination with neurological symptoms, and characteristics of patients with and without encephalitis were compared. The aim was to identify risk factors for viral encephalitis, the spectrum of causative organisms, the onset time, the clinical features, the type and efficacy of encephalitis treatment and the outcome in this setting.…”