HEMATOPOETİK KÖK HÜCRE NAKLİ VE SİTOMEGALOVİRÜS İNFEKSİYONU: DEĞİŞEN KLİNİK, TANI VE TEDAVİ

Öz

Sitomegalovirus (CMV) enfeksiyonu hematopoetik kök hücre naklinden sonra morbidite ve mortalitenin önemli bir nedeni olarak yer almaktadır. Günümüzde CMV patogenezinin anlaşılması ve gelişen modern laboratuvar teknikleri ile virüsün erken tespiti ve uygun antiviral ile tedavisinde önemli ilerlemeler kaydedilmiştir. CMV infeksiyonu için yüksek riskli kök hücre alıcılarının belirlenmesi ve bunların gansiklovir ile profilaktik olarak (nakilden sonra engrafmandan başlayarak 100.güne kadar) veya preemptif (CMV infeksiyonu tespit edildikten sonra hastalığın gelişmesinin önlenmesi) tedavisi bu yazıda önemli çalışmalar ışığında özetlenmiştir.

Anahtar Kelimeler

• Kök hücre nakli, sitomegalovirüs, gansiklovir

Kaynakça

1. Avery RK, Adal KA, Longworth DL, Bolwell BJ. A survey of al- logeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy pre-emptive therapy. Bone Marrow Transplant 2000; 26:763-7.
2. Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA. Cytomegalovirus pp65 antigenemia guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: randomized double-blind study. Blood 1996; 88:4063-4071.
3. Boeckh M, Nichols WG. The impact of cytomegalovirus serosta- tus of donor and recipient before hematopoietic stem cell transp- lantation in the era of antiviral prophylaxis and preemptive the- rapy. Blood 2004; 103: 2003-2008.
4. Broers AE, van Der Holt R, van Esser JW, Gratama JW, Henzen- Logmans S, Kuenen-Boumeester V, Löwenberg B, and Cornelis- sen JJ. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplan- tation. Blood 2000; 95: 2240-2245.
5. Britt W, Alford C: Cytomegalovirus. In: Virology. Philadelphia, Pa: Lippincott Raven; 1996, p. 2493.
6. Einsele H, Ehninger G, Hebart H, Wittkowski KM, Schuler U, Jahn G, Mackes P, Herter M, Klingebiel T, Loffler J, Wagner S, Muller CA. Polymerase chain reaction monitoring reduces the in- cidence of cytomegalovirus disease and the duration and side ef- fects of antiviral therapy after bone marrow transplantation. Blo- od 1995; 86:2815-2820.
7. Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Löffler J, Grigoleit U, Moris A, Rammensee HG, Kanz L, Kleihauer A, Frank F, Jahn G, and Hebart H. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002; 99: 3916- 3922.
8. Falk CS, Mach M, Schendel DJ, Weiss EH, Hilgert I, Hahn G. NK cell activity during human cytomegalovirus infection is do- minated by US2-11-mediated HLA class I down-regulation. J Im- munol 2002; 169:3257-3266.

9. Gratama JW, van Esser JW, Lamers CH, et al. Tetramer-based qu- antification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transp- lantation may identify patients at risk for progressive CMV infec- tion. Blood 2001;98:1358-1364.
10. Howden BP, Michaelides A, Spelman DW, Spencer A, Schwarer AP, Wesselingh S, Kotsimbos TC. Cytomegalovirus viral load monitoring after allogeneic bone marrow transplantation in pati- ents receiving antiviral prophylaxis. Bone Marrow Transplant 2003;32:795-800.
11. Kim DH , Kim JG, Lee NY, Sung WJ, Sohn SK, Suh JS, Lee KS, and Lee KB. Risk f actors for late cytomegalovirus infecti- on after allogeneic stem cell transplantation using HLA-matched sibling donor: donor lymphocyte infusion and previous history of early CMV infection. Bone Marrow Transplant 2004; 34: 21-27.
12. Lacey SF, Diamond DJ, Zaia AJ. Assessment of cellular immunity to human cytomegalovirus in recipients of allogeneic stem cell transplants. Biol Blood Marrow Transplant 2004; 10:433-447.
13. Limaye AP, Raghu G, Koelle DM, Ferrenberg J, Huang ML, Bo- eckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis 2002; 185: 20-27.
14. Ljungman P, Deliliers GL, Platzbecker U, Matthes-Martin S, Ba- cigalupo A, Einsele H, Ullmann J, Musso M, Trenschel R, Riba- ud P, Bornhäuser M, Cesaro S, Crooks B, Dekker A, Gratecos N, Klingebiel T, Tagliaferri E, Ullmann AJ, Wacker P, and Cordon- nier C. Cidofovir for cytomegalovirus infection and disease in al- logeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 2001; 97:388-392.
15. Meijer E, Boland G, Verdonck LF. Prevention of Cytomegalovi- rus Disease in Recipients of Allogeneic Stem Cell Transplants. Clinical Microbiology Reviews 2003; 16: 647-657.
16. Murayama T, Takegoshi M, Tanuma J, Eizuru Y. Analysis of hu- man cytomegalovirus UL144 variability in low-passage clinical isolates in Japan. Intervirology 2005; 48:201-206.
17. Narvios AB, de Lima M, Shah H, Lichtiger B. Transfusion of le- ukoreduced cellular blood components from cytomegalovirus- unscreened donors in allogeneic hematopoietic transplant recipi- ents: Analysis of 72 recipients. J Exp Med 2005; 202:499-501.
18. Quinnan GV, Kirmani N, Rook AH, Manischewitz JF, Jackson L, Moreschi G, Santos GW, Saral R, Burns WH. Cytotoxic T cells in cytomegalovirus infection. HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant reci- pients. N Engl J Med 1982;307:7-13
19. Ozdemir E, John L, Gillespie G, Rowland-Jones S, Champlin R, Molldrem JJ, Komanduri KV. Cytomegalovirus reactivation fol- lowing allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells. Blood 2002: 100; 3690-3697.
20. Park B, Oh H, Lee S, Song Y, Shin J, Sung YC, Hwang SY, Ahn K. The MHC class I homolog of human cytomegalovirus is resis- tant to down-regulation mediated by the unique short region pro- tein (US) 2, US3, US6, and US11 gene products. J Immunol 2002; 168:3464-3469.
21. Reusser P. Cytomegalovirus infection and disease after bone mar- row and solid organ transplantation. Baillieres Clin Infect Dis 1996; 3: 357-371.
22. Reusser P, Einsele H, Lee J, Volin L, Rovira M, Engelhard D, Fin- ke J, Cordonnier C, Link H, and Ljungman P. Randomized mul- ticenter trial of foscarnet versus ganciclovir for preemptive the- rapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood 2002; 99: 1159-1164.
23. Stocchi R, Ward K, Fanin R, Baccarani M, Apperley J. Manage- ment of human cytomegalovirus infection and disease after allo- geneic bone marrow transplantation. Haematologica 1998; 84:71-79.
24. Yue Y, Zhou SS, Barry PA. Humoral immune response to functi- onal regions of human cytomegalovirus glycoprotein B. J Gen Virol 2003; 84:3371-3379.
25. Zaia JA. Prevention and management of CMV-related problems after hematopoetic stem cell transplantation. Bone Marrow Transplant 2002; 29:633-638.