Viral infections in bone marrow transplant recipients: From the bench to the bedside

G. Gerna, F. Baldanti, D. Lilleri, L. De-Giuli, M. G. Revello

Research output: Contribution to journalArticlepeer-review

Abstract

Viral infections are still a major complication of bone marrow transplants (BMT), as well as solid organ transplants (SOT), mainly due to immunosuppressive regimens. Human Cytomegalovirus (HCMV) infections play a major role in the post-transplant pathology and involve a great part of transplanted patients. Primary HCMV infections are the most severe, often causing the appearance of clinical symptoms which can range from a febrile syndrome with leukopenia and thrombocytopenia, to organ localization involving mostly the lungs, the gastrointestinal tract and the eyes. In addition, HCMV is considered to cause immunosuppression. Diagnosis of systemic infection is based upon the determination and quantification of viremia (measuring the infectious virus in blood leukocytes), pp65- antigenemia (measuring the number of the cells carrying this excess of viral protein) and plasma- and/or leuko-DNAemia (quantifying the number of viral DNA copies per volume unit of plasma or whole blood, or per 1x10 5 leukocytes). More recently introduced assays, which must be thoroughly defined, are the determination of immediate-early and late viral transcripts, and the detection of circulating cytomegalic endothelial cells. In our hospital, in order to prevent the appearance of HCMV-related clinical symptoms and disease, a preemptive therapy approach is used. Using antigenemia as a routine reference test, antiviral treatment with either ganciclovir or foscarnet is initiated upon the first HCMV appearance in blood (which must be confirmed within a couple of days). This approach is currently used in BMT recipients (as well as in SOT recipients with primary infection). Other centers may use DNAemia as a parameter for initiating treatment. This might cause unnecessary treatment of patients with transitory or abortive HCMV infection detected by polymerase chain reaction and not by antigenemia. Antiviral drug resistance may occur, but is not frequent using preemptive therapy. The other Herpes virus which may cause severe pathology is Epstein- Barr virus (EBV), which is responsible for post-transplant lymphoproliferative disorders (PTLD) mainly due to the degree of the immunosuppressive regimen. Reduction of immunosuppression rapidly improves PTLD, while in a more advanced stage, infusion of EBV-specific cytotoxic T cells may represent the unique effective therapy. The role of other Herpes viruses, such as HSV (Herpes simplex virus), VZV (Varicella zoster virus), HHV-6 (human Herpes virus), HHV-8, and other viruses, such as human adenoviruses and respiratory syncytial virus, must also be taken into consideration. In conclusion, modulation of the immunosuppressive regimen in association with the adoption of the most up-to-date approaches in the field of chemotherapy and immunotherapy appears to provide the clinician with effective tools for controlling viral infections in the post-transplant period.

Original languageEnglish
Pages (from-to)84-106
Number of pages23
JournalReviews in Clinical and Experimental Hematology
Issue number7
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Hematology

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