Publications by authors named "Sanna Aalto"

3 Publications

  • Page 1 of 1

Retrospective evaluation of serum Epstein Barr virus DNA levels in 406 allogeneic stem cell transplant patients.

Haematologica 2007 Jun;92(6):819-25

Helsinki University Central Hospital, Department of Medicine, Helsinki, Finland.

Background And Objectives: An HLA-mismatched donor and a T-cell-depleted graft are known risk factors for Epstein-Barr virus (EBV) reactivation after stem cell transplantation. We studied the frequency and outcome of serum EBV DNA levels in patients transplanted with an unmanipulated graft from an HLA-identical donor.

Design And Methods: Overall, 5479 serial serum samples from 406 consecutive allogeneic stem cell transplant recipients were analyzed retrospectively for EBV DNA with quantitative polymerase chain reaction (PCR).

Results: EBV DNA was found in the serum of 56 of the 406 patients (14%). EBV positivity was seen in 9 % of the recipients of a graft from a sibling donor and in 29 % of those with an unrelated donor. EBV-PCR positivity resolved without specific treatment in a third of the cases, in another third the copy number increased progressively or was high in the last serum sample, and in the remaining third the copy numbers were low in all positive sera including the last sample. In multivariate analysis antithymocyte globulin given for any reason and grade III-IV acute graft-versus-host disease were the only statistically significant risk factors for EBV reactivation. Only 8/56 patients with EBV-DNA positivity were alive at the time of the present analysis. The outcome of EBV-PCR positivity could not be predicted by the copy number or the timing of the first positive sample.

Interpretation And Conclusions: EBV reactivation was a common phenomenon in allogenic stem cell transplant recipients. In many patients the viremia resolved without EBV-directed treatment. Severe acute graft-versus-host disease and antithymocyte globulin given for any reason were risk factors for EBV viremia.
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June 2007

Monitoring of EBV-DNAemia by quantitative real-time PCR after adult liver transplantation.

J Clin Virol 2006 Oct 22;37(2):104-8. Epub 2006 Aug 22.

Department of Virology, HUSLAB, Helsinki University Central Hospital and University of Helsinki, FIN-00290 Helsinki, Finland.

Background: Post-transplant lymphoproliferative disease (PTLD) causes significant morbidity and mortality in transplantation. The clinical significance of Epstein-Barr virus (EBV) in the development of PTLD is clear, but not all EBV-reactivations cause PTLD.

Objectives: We retrospectively analyzed EBV-DNAemia in liver transplant patients by a quantitative TaqMan-based real-time plasma PCR.

Study Design: Altogether 1284 specimens, obtained from 105 patients for frequent monitoring of cytomegalovirus (CMV) and human herpesvirus-6 and -7 (HHV-6, HHV-7) during the post-transplant year, were retrospectively tested for EBV-DNA.

Results: Altogether, 14/105 (13%) patients showed EBV-DNAemia, which usually occurred within 3 months after transplantation and subsided within a few weeks. EBV-DNAemia occurred concurrently with CMV in 10/14, with HHV-6 in 11/14, and with all three betaherpesviruses in 4/14 cases. The peak viral loads were relatively low (median 2100 EBV-DNA copies/ml, range 568-6600), except in one patient who first had low-level EBV-DNA (562-3022 copies/ml) in the early post-transplant period, but on day 175 after transplantation developed high-level DNAemia (9851-86,975copies/ml) which continued for 6 months and developed into PTLD at 6 months after transplantation.

Conclusion: Low-level EBV-DNAemia is common after liver transplantation, often occurring together with betaherpesviruses, but seldom leads to high viral loads or PTLD. However, monitoring of EBV-DNA levels in the patients can be useful.
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October 2006

Lymphoproliferative disease after allogeneic stem cell transplantation--pre-emptive diagnosis by quantification of Epstein-Barr virus DNA in serum.

J Clin Virol 2003 Dec;28(3):275-83

Department of Virology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, FIN-00290 Helsinki, Finland.

Background: Lymphoproliferative disease (PTLD) is a life-threatening complication of organ transplantation. In matched, allogeneic, non-T-cell-depleted stem-cell transplantations (SCT) the disease develops early but has been thought to be rare.

Objectives: We determined by strict histopathological criteria the incidence of fatal Epstein-Barr-virus (EBV)-related PTLD in a large number of SCT, and assessed the diagnostic value of a real-time quantitative polymerase chain reaction (qPCR) for EBV-DNA in serum specimens.

Study Design: Of the 257 SCT performed in Helsinki during 1994-1999, 132 (51%) recipients were alive and 125 (49%) had succumbed by June 2001. The necropsies were analyzed for EBV-related PTLD as evidenced by disseminated lymphocytic infiltrates labeled histochemically for antigens and RNA (EBER 1 and 2) detectable by in situ technology. From a subset of the PTLD cases (N=12) and a series of corresponding stem-cell recipient controls (N=36), consecutive samples of serum (N=103 and 364, respectively) were studied by qPCR for EBV-DNA, and the clinical data were reviewed.

Results: The post-mortem analysis revealed 18 cases of PTLD (14% of the deceased), all of whom had received intensive immunosuppressive treatment including anti-thymocyte globulin for treatment or prophylaxis of graft versus host disease (GVHD). By using qPCR all the PTLD patients became EBV-DNA positive, in progressively rising copy numbers. EBV-DNA was first detectable 70 (median; range 24-154) days after SCT or 23 (4-86) days before death; i.e. earlier than the symptoms which appeared 15 (2-85) days before death. Among the SCT controls, EBV-DNA occurred sporadically (in only 3.9% sera).

Conclusions: qPCR for EBV-DNA in serum is a highly sensitive (100%) and specific (96%) diagnostic approach. Intensely immunosuppressed stem-cell recipients are at a great risk of developing PTLD, and should be carefully monitored for EBV-DNA, for pre-emptive treatment of this life-threatening disorder.
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December 2003