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

被引:32
作者
Aalto, SM
Juvonen, E
Tarkkanen, J
Volin, L
Ruutu, T
Mattila, PS
Piiparinen, H
Knuutila, S
Hedman, K [1 ]
机构
[1] Univ Helsinki, Haartman Inst, Dept Virol, Helsinki, Finland
[2] Univ Helsinki, Cent Hosp, FIN-00290 Helsinki, Finland
[3] HUCH, Dept Med, Helsinki, Finland
[4] Univ Helsinki, Haartman Inst, Dept Pathol, Helsinki, Finland
[5] HUCH, Dept Otorhinolaryngol, Helsinki, Finland
[6] Univ Helsinki, Haartman Inst, Dept Med Genet, Helsinki, Finland
关键词
B-cell; bone marrow; lyraphoproliferative disorder; herpes virus; PCR; stem cell;
D O I
10.1016/S1386-6532(03)00022-2
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 I 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. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:275 / 283
页数:9
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