Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation

Öz:

Introduction: It is controversial that cytomegalovirus (CMV) replication is a cause of graft-versus-host disease (GVHD). The aim of this study is to evaluate whether CMV replication causes acute GVHD development or not. Materials and methods: The study is retrospective. Patients diagnosed with acute GVHD with a prior history of allogeneic hematopoietic cell transplantation (allo-HCT) were included in the study. All the included patients were followed-up in the bone marrow transplantation unit between 01/01/2013- 10/31/2019. As the control group, patients without a history of acute GVHD after allo-HCT were included. The data of patients with acute GVHD after allo-HCT and patients with out known acute GVHD were compared. Results: Fifty nine patients with acute GVHD and 178 patients without acute GVHD after allo-HCT were included in the study. Sixteen of the patients with acute GVHD were female and 43 were male. Sixty two of the patients without acute GVHD were female and 116 were male. The average CMVDNA level was found as 1871.0 [821.0-16720.0] copies/ml in patients who had CMV replication in the acute GVHD group. On the other hand, the average of CMV-DNA level was found as 1607.5 [601.0- 119181.0] copies/ml in the non-acute GVHD group. There was no statistically significant difference between the two groups. Discussion: CMV replication does not seem to contribute to acute GVHD development after allo-HCT. Suppression of CMV replication may not prevent acute GVHD development.

Anahtar Kelime:

Allojenik Hematopoietik Kök Hücre Transplantasyonlu Hastalarda Sitomegalovirüs Replikasyonu ve Akut Graft-Versus-Host Hastalığı Arasındaki İlişkinin Değerlendirilmesi

Öz:

Giriş: Sitomegalovirus (CMV) replikasyonunun, graft-versus-host hastalığının (GVHH) bir nedeni olduğu tartışmalıdır. Bu çalışmanın amacı CMV replikasyonunun akut GVHH gelişimine neden olup olmadığını değerlendirmektir. Gereç ve yöntemler: Çalışma, geriye dönüktür. Daha önceden allojenik hematopoietik hücre nakli (allo-HHN) öyküsü olan akut GVHH tanısı alan hastalar çalışmaya dahil edilmiştir. Dahil edilen tüm hastalar 01/01/2013-31/10/2019 tarihleri arasında kemik iliği nakil ünitesinde takip edilmiştir. Kontrol grubu olarak, allo-HHN sonrası akut GVHH öyküsü olmayan hastalar alınmıştır. Allojenik hematopoietik hücre naklinden sonra akut GVHH'si olan hastalar ile nakil sonrası bilinen akut GVHH'si olmayan hastaların verileri karşılaştırılmıştır. Bulgular: Allojenik hematopoietik hücre naklinden sonra akut GVHH'li 59 hasta ve akut GVHH'si olmayan 178 hasta çalışmaya dahil edilmiştir. Akut GVHH'li hastaların 16'sı kadın, 43'ü erkektir. Akut GVHH olmayan hastaların 62'si kadın, 116'sı erkektir. Akut GVHH grubunda CMV replikasyonu olan hastalarda ortalama CMV-DNA düzeyi 1871,0 [821,0-16720,0] kopya/ml bulunmuştur. Akut olmayan GVHH grubunda ise CMV-DNA düzeyi ortalaması 1607,5 [601,0-119181,0] kopya/ml bulunmuştur. İki grup arasında istatistiksel olarak anlamlı bir fark saptanmamıştır. Tartışma: CMV replikasyonunun, allo-HHN sonrası akut GVHD gelişimine katkıda bulunmadığı görülmektedir. CMV replikasyonunun baskılanması akut GVHH gelişimini engellemeyebilir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med. 2007; 357: 1472-1475.
2. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009; 113(23): 5711-9.
3. Miller W, Flynn P, Mc Cullough J, et al. Cytomegalovirus infection after bone marrow transplantation: an association with acute graftv- host disease. Blood. 1986; 67(4): 1162-7.
4. Martino R, Rovira M, Carreras E, et al. AlloPBSCT and Infectious/Non-infectious Complications Subcommittes of the Grupo Español de Trasplante Hematopoyético (GETH). Severe infections after allogeneic peripheral blood stem cell transplantation: a matched-pair comparison of unmanipulated and CD341 cellselected transplantation. Haematologica. 2001;86(10):1075-86.
5. Ljungman P, Perez-Bercoff L, Jonsson J, et al. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica. 2006; 91(1): 78-83.
6. Appleton AL, Sviland L. Pathogenesis of GVHD: role of herpes viruses. Bone Marrow Transplant. 1993; 11(5): 349-55.
7. Wang LR, Dong LJ, Zhang MJ, Lu DP. Correlations of human herpes virus 6B and CMV infection with acute GVHD in recipients of allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant. 2008; 42(10): 673-7.
8. Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol. 2007; 25: 139–70.
9. Hill LQ, Alousi A, Kebriaei P, Mehta R, Rezvani K, Shpall E. New and emerging therapies for acute and chronic graft versus host disease. Ther Adv Hematol. 2018; 9(1):21–46.
10. Pidala J, Anasetti C. Glucocorticoid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16(11):1504–18.
11. Vigorito AC, Campregher PV, Storer BE, etal. National Institutes of Health. Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD. Blood. 2009; 114(3): 702-8.
12. Vogelsang GB, Lee L, Bensen-Kennedy DM. Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant. Annu Rev Med. 2003; 54: 29–52.
13. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graftversus- host disease: initial treatment. Blood 1990; 76(8): 1464–72.
14. Ljungman P, Reusser P, Einsele H, Engelhard D, Ward K, Cordonnier C for the Infectious Diseases Working Partyof the European Group for Blood and Marrow Transplantation. Management of CMV infections: recommendations from the infectious diseases working party of the EBMT. Bone Marrow Transplant. 2004; 33: 1075–1081.
15. Grefte A, van der Giessen M, van Son W, The TH. Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis. 1993; 167(2): 270-7.
16. Broers AE, van Der Holt R, van Esser JW, et al. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. Blood. 2000;9 5(7): 2240-5.
17. Ringdén O, Pihlstedt P, Markling L, et al. Prevention of graft-versus-host disease with T cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients. Bone Marrow Transplant. 1991; 7(3): 221-6.
18. Carlens S, Ringden O, Remberger M, et al Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis. Bone Marrow Transplant. 1998; 22(8): 755-61.
19. Meyers JD, Reed EC, Shepp DH, et al. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. N Engl J Med. 1988; 318(2): 70-75.
20. Cantoni N, Hirsch HH, Khanna N, et al. Evidence for a bidirectional relationship between cytomegalovirus replication and acute graftversus- host disease. Biol Blood Marrow Transplant. 2010; 16(9): 1309-14.
21. Tomblyn M, Chiller T, Einsele H, et ak. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15(10): 1143-238.

APA	Mert D, Merdin A, Uncu Ulu B, DAL M, Kızıl Çakar M, iskender g, Ceken S, Yiğenoğlu T, Altuntas F, ERTEK M (2021). Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. , 233 - 238. 10.5505/aot.2021.30643
Chicago	Mert Duygu,Merdin Alparslan,Uncu Ulu Bahar,DAL MEHMET SINAN,Kızıl Çakar Merih,iskender gülşen,Ceken Sabahat,Yiğenoğlu Tuğçe Nur,Altuntas Fevzi,ERTEK MUSTAFA Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. (2021): 233 - 238. 10.5505/aot.2021.30643
MLA	Mert Duygu,Merdin Alparslan,Uncu Ulu Bahar,DAL MEHMET SINAN,Kızıl Çakar Merih,iskender gülşen,Ceken Sabahat,Yiğenoğlu Tuğçe Nur,Altuntas Fevzi,ERTEK MUSTAFA Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. , 2021, ss.233 - 238. 10.5505/aot.2021.30643
AMA	Mert D,Merdin A,Uncu Ulu B,DAL M,Kızıl Çakar M,iskender g,Ceken S,Yiğenoğlu T,Altuntas F,ERTEK M Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. . 2021; 233 - 238. 10.5505/aot.2021.30643
Vancouver	Mert D,Merdin A,Uncu Ulu B,DAL M,Kızıl Çakar M,iskender g,Ceken S,Yiğenoğlu T,Altuntas F,ERTEK M Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. . 2021; 233 - 238. 10.5505/aot.2021.30643
IEEE	Mert D,Merdin A,Uncu Ulu B,DAL M,Kızıl Çakar M,iskender g,Ceken S,Yiğenoğlu T,Altuntas F,ERTEK M "Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation." , ss.233 - 238, 2021. 10.5505/aot.2021.30643
ISNAD	Mert, Duygu vd. "Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation". (2021), 233-238. https://doi.org/10.5505/aot.2021.30643

APA	Mert D, Merdin A, Uncu Ulu B, DAL M, Kızıl Çakar M, iskender g, Ceken S, Yiğenoğlu T, Altuntas F, ERTEK M (2021). Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. ACTA ONCOLOGICA TURCICA, 54(2), 233 - 238. 10.5505/aot.2021.30643
Chicago	Mert Duygu,Merdin Alparslan,Uncu Ulu Bahar,DAL MEHMET SINAN,Kızıl Çakar Merih,iskender gülşen,Ceken Sabahat,Yiğenoğlu Tuğçe Nur,Altuntas Fevzi,ERTEK MUSTAFA Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. ACTA ONCOLOGICA TURCICA 54, no.2 (2021): 233 - 238. 10.5505/aot.2021.30643
MLA	Mert Duygu,Merdin Alparslan,Uncu Ulu Bahar,DAL MEHMET SINAN,Kızıl Çakar Merih,iskender gülşen,Ceken Sabahat,Yiğenoğlu Tuğçe Nur,Altuntas Fevzi,ERTEK MUSTAFA Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. ACTA ONCOLOGICA TURCICA, vol.54, no.2, 2021, ss.233 - 238. 10.5505/aot.2021.30643
AMA	Mert D,Merdin A,Uncu Ulu B,DAL M,Kızıl Çakar M,iskender g,Ceken S,Yiğenoğlu T,Altuntas F,ERTEK M Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. ACTA ONCOLOGICA TURCICA. 2021; 54(2): 233 - 238. 10.5505/aot.2021.30643
Vancouver	Mert D,Merdin A,Uncu Ulu B,DAL M,Kızıl Çakar M,iskender g,Ceken S,Yiğenoğlu T,Altuntas F,ERTEK M Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation. ACTA ONCOLOGICA TURCICA. 2021; 54(2): 233 - 238. 10.5505/aot.2021.30643
IEEE	Mert D,Merdin A,Uncu Ulu B,DAL M,Kızıl Çakar M,iskender g,Ceken S,Yiğenoğlu T,Altuntas F,ERTEK M "Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation." ACTA ONCOLOGICA TURCICA, 54, ss.233 - 238, 2021. 10.5505/aot.2021.30643
ISNAD	Mert, Duygu vd. "Evaluation of the Relationship Between Cytomegalovirus Replication and Acute Graft-Versus-Host Disease in Patients with Allogeneic Hematopoietic Stem Cell Transplantation". ACTA ONCOLOGICA TURCICA 54/2 (2021), 233-238. https://doi.org/10.5505/aot.2021.30643