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Pathogenesis and Biology of Graft-Versus-Host Disease

Year 2020, Volume: 20 Issue: 3, 115 - 119, 29.12.2020

Abstract

Graft-versus-host disease (GvHD) is an important complication that usually develops after hematopoietic stem cell transplantation and affects the success of the transplant. It is important to identify the pathogenesis, risk factors, prognosis, and biomarkers for the management and prevention of GvHD, as welll as the development of treatment strategies for GvHD. This review presents current literature studies on factors that affect GvHD biology, including classical and nonclassical human leukocyte antigen (HLA) genes, minor HLA antigens, cytokines, chemokines, and costimulatory molecules.

References

  • 1. Ferrara JL, Reddy P. Pathophysiology of graft versus-host disease. Semin Hematol 2006;43(1):3-10.
  • 2. Penack O, Marchetti M, Ruutu T, Aljurf M, Bacigalupo A, Bonifazi F, et al. Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 2020 Feb;7(2):e157-e167.
  • 3. Carpenter PA, MacMillan ML. Management of acute graft-versus-host disease in children. Pediatr Clin North Am 2010 Feb;57(1):273-95.
  • 4. Patel KK, Patel AK, Ranjan RR, Shah AP. Transfusion associated graft versus host disease following whole blood transfusion from an unrelated donor in an ımmunocompetent patient. Indian J Hematol Blood Transfus 2010 Sep;26(3):92-5.
  • 5. Saffo S, Peng C, Kibbi N, Patel N, Robert ME, Adekolu E, et al. Graftversus- host disease after pancreatic transplantation. ACG Case Rep J 2019 Sep 12;6(9):e00214.
  • 6. Batra A, Cottler-Fox M, Harville T, Rhodes-Clark BS, Makhoul I, Nakagawa M. Autologous graft versus host disease: An emerging complication in patients with multiple myeloma Bone Marrow Res 2014;2014:891427.
  • 7. Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 2012 Jan 5;119(1):296-307.
  • 8. Billingham RE. The biology of graft-versus-host reactions. Harvey Lectures 1966-67;62:21-78.
  • 9. Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003 Jul 15;102(2):756-62.
  • 10. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005 Dec;11(12):945-56.
  • 11. Pavletic SZ, Vogelsang GB, Lee SJ. 2014 National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Preface to the series. Biol Blood MarrowTranspl 2015 Mar;21(3):387-8.
  • 12. Apostolova P, Zeiser R. The role of danger signals and ectonucleotidases in acute graft-versus- host disease. Hum Immunol 2016 Nov;77(11):1037-47.
  • 13. Zeiser R, Penack O, Holler E, Idzko M. Danger signals activating innate immunity in graft-versus-host disease. J Mol Med(Berl) 2011 Sep;89(9):833-45.
  • 14. Reddy P. Pathopysiology of acute graft versus host disease. Hematol Oncol 2003 Dec:21(4):149-61.
  • 15. Sung AD, Chao NJ. Acute graft-versus-host disease: Are we close to bringing the bench to the bedside? Best Pract Res Clin Haematol 2013 Sep;26(3):285-92.
  • 16. Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, et al. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011 Nov 3;118(18):5011-20.
  • 17. Socié G, Ritz J. Current issues in chronic graft-versus-host disease. Blood 2014 Jul 17;124(3):374-84.
  • 18. Sarantopoulos S, Ritz J. Aberrant B-cell homeostasis in chronic GVHD. Blood 2015 Mar 12;125(11):1703-7.
  • 19. Zeiser R, Blazar BR. Pathophysiology of chronic graft versus host disease and therapeutic targets. N Engl J Med 2017 Dec 28;377(26):2565-2579.
  • 20. Ghimire S, Weber D, Mavin E, Wang, XN, Dickinson, AM, Holler, E. Pathophysiology of GvHD and other HSCT-related major complications. Front Immunol 2017 Mar 20;8:79.
  • 21. Qayed M, Wang T, Hemmer MT, Spellman S, Arora M, Couriel D, et al. Influence of age on acute and chronic GVHD in children undergoing HLA-identical sibling bone marrow transplantation for acute leukemia: Implications for prophylaxis. Biol Blood MarrowTransplant 2018 Mar;24(3):521-8.
  • 22. Vignon M, Andreoli A, Dhédin N, Lebgline E, Masson E, Robin M, et al. Graft-versus-host disease in adolescents and young adults (15-24 years old) after allogeneic hematopoietic stem cell transplantation for acute leukemia in first complete remission. J Adolesc Young Adult Oncol 2017 Jun;6(2):299-306.
  • 23. Carlberg V, Simons E, Delano S, Huang JT. Pediatric Graft- Versus-Host Diease In: Cotliar JA, eds. Atlas of Graft-Versus-Host Diease: Approaches to Diagnosis and Treatment. Cham, 1st ed. Switzerland: Springer International Publishing AG, 2017:105-23.
  • 24. Gatza E, Reddy P, Choi SW. Prevention and treatment of acute graftversus- host disease in children, adolescents, and young adults. Biol Blood Marrow Transplant 2020 May;26(5):e101-e112.
  • 25. Hosseini E, Schwarer AP, Ghasemzadeh M. The impact of HLA-E polymorphisms in graft-versus-host disease following HLA-E matched allogeneic hematopoietic stem cell transplantation. Iran J Allergy Asthma Immunol 2012;11(1):15-21.
  • 26. Hosseini E, Schwarer AP, Ghasemzadeh M. Do human leukocyte antigen E polymorphisms influence graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation? Exp Hematol 2015 Mar;43(3):149-57.
  • 27. The IMGT/HLA Database; http://www.ebi.ac.uk/imgt/hla/stats. html Erişim tarihi: 27.03.2014
  • 28. Meyer D, Aguriar VRC, Bitarello BD, Brandt DYC, Nunes K. A genomic perspective on HLA evolution. Immunogenetics 2018 Jan;70(1):5-27.
  • 29. Edgerly CH, Weimer ET. The Past, present, and future of HLA typing in transplantation. Methods Mol Biol 2018;1802:1-10.
  • 30. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor recipient HLA matching contributest othe success of unrelated donor marrow transplantation. Blood 2007 Dec 15;110(13):4576-83.
  • 31. Touzeau C, Gagne K, Sebille V, Herry P, Chevallier P, Follea G, et al. Investigation of the impact of HLA-DPB1 matching status in 10/10 HLA matched unrelated hematopoietic stem cell transplantation: results of a French single center study. Hum Immunol 2012 Jul;73(7):711-4.
  • 32. Crocchiolo R, Zino E, Vago L, Oneto R, Bruno B, Pollichieni S, et al. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation. Blood 2009 Aug 13;114(7):1437-44.
  • 33. Rene C, Lozano C, Eliaou JF. Expression of classical HLA class I molecules: regulation and clinical impacts: Julia Bodmer award review 2015. HLA 2016 May;87(5):338-49.
  • 34. Summers C, Sheth VS, Bleakley M. Minor histocompatibility antigen-specific T cells. Front Pediatr 2020 Jun3;8:284.
  • 35. Roy DC, Perreault C. Major vs minor histocompatibility antigens. Blood 2017 Feb 9;129(6):664-6.
  • 36. Akatsuka Y, Warren EH, Gooley TA, Brickner AG, Lin MT, Hansen JA, et al. Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling. Br J Haematol 2003 Nov;123(4):671-5.
  • 37. McCarroll SA, Bradner JE, Turpeinen H, Volin L, Martin PJ, Chilewski SD, et al. Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease. Nat Genet 2009 Dec;41(12):1341-4.
  • 38. Martin PJ, Levine DM, Storer BE, Warren EH, Zheng X, Nelson SC et al. Genome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease. Blood 2017 Feb 9;129(6):791-8.
  • 39. Mohty M, Blaise D, Faucher C, Vey N, Bouabdallah R, Stoppa AM, et al. Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2005 Dec 15;106(13):4407-11.
  • 40. Henden AS, Hill GR. Cytokines in graft-versus-host disease. J Immunol 2015 May 15;194(10):4604-12.
  • 41. Kumar S, Mohammadpour H, Cao X. Targeting cytokines in GVHD therapy. J Immunol Res Ther 2017;2(1):90-9.
  • 42. Yi T, Chen Y, Wang L, Du G, Huang D, Zhao D, et al. Reciprocal differentiation and tissue- specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood 2009 Oct 1;114(14):3101-12.
  • 43. Hüber CM, Doisne JM, Colucci F. IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation. Eur J Immunol 2015 Jun;45(6):1727-35.
  • 44. Taylor PA, Panoskaltsis-Mortari A, Freeman GJ, Sharpe AH, Noelle RJ, Rudensky AY, et al. Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM). Blood 2005 Apr 15;105(8):3372-80.
  • 45. Zeiser R, Blazar BR. Acute graft versus host disease-biologic process, prevention and therapy. N Engl J Med 2017 Nov 30;377(22):2167- 79.
  • 46. Ijaz A, Khan AY, Malik SU, Faridi W, Fraz MA, Usman M, et al. Significant risk of graft-versus-host disease with exposure to checkpoint inhibitors before and after allogeneic transplantation. Biol Blood Marrow Transplant 2019 Jan;25(1):94-9.
  • 47. Haverkos BM, Abbott D, Hamadani M, Armand P, Flowers ME, Merryman E, et al. PD-1 blockade for relapsed lymphoma postallogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 2017 Jul 13;130(2):221-8.

GvHH Patogenezi ve Biyolojisi

Year 2020, Volume: 20 Issue: 3, 115 - 119, 29.12.2020

Abstract

Graft versus host hastalığı (GvHH) genellikle hematopoetik kök hücre nakli (HKHN) sonrası gelişen ve nakil işleminin başarısını etkileyen önemli bir komplikasyondur. GvHH’nin iyi yönetilmesi, önlenmesi ve tedavi stratejilerinin geliştirilebilmesi için patogenezi, risk faktörleri, prognozu ve biyobelirteçlerinin tespit edilmesi önemlidir. Bu derlemede GvHH biyolojisinde etkili olan faktörlerden klasik ve klasik olmayan insan lökosit antijenleri (HLA) genleri, minör HLA antijenleri, sitokinler, kemokinler ve kostimülatör moleküller ile ilgili literatürde yer alan güncel çalışmalar sunulmuştur.

References

  • 1. Ferrara JL, Reddy P. Pathophysiology of graft versus-host disease. Semin Hematol 2006;43(1):3-10.
  • 2. Penack O, Marchetti M, Ruutu T, Aljurf M, Bacigalupo A, Bonifazi F, et al. Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol 2020 Feb;7(2):e157-e167.
  • 3. Carpenter PA, MacMillan ML. Management of acute graft-versus-host disease in children. Pediatr Clin North Am 2010 Feb;57(1):273-95.
  • 4. Patel KK, Patel AK, Ranjan RR, Shah AP. Transfusion associated graft versus host disease following whole blood transfusion from an unrelated donor in an ımmunocompetent patient. Indian J Hematol Blood Transfus 2010 Sep;26(3):92-5.
  • 5. Saffo S, Peng C, Kibbi N, Patel N, Robert ME, Adekolu E, et al. Graftversus- host disease after pancreatic transplantation. ACG Case Rep J 2019 Sep 12;6(9):e00214.
  • 6. Batra A, Cottler-Fox M, Harville T, Rhodes-Clark BS, Makhoul I, Nakagawa M. Autologous graft versus host disease: An emerging complication in patients with multiple myeloma Bone Marrow Res 2014;2014:891427.
  • 7. Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 2012 Jan 5;119(1):296-307.
  • 8. Billingham RE. The biology of graft-versus-host reactions. Harvey Lectures 1966-67;62:21-78.
  • 9. Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003 Jul 15;102(2):756-62.
  • 10. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005 Dec;11(12):945-56.
  • 11. Pavletic SZ, Vogelsang GB, Lee SJ. 2014 National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Preface to the series. Biol Blood MarrowTranspl 2015 Mar;21(3):387-8.
  • 12. Apostolova P, Zeiser R. The role of danger signals and ectonucleotidases in acute graft-versus- host disease. Hum Immunol 2016 Nov;77(11):1037-47.
  • 13. Zeiser R, Penack O, Holler E, Idzko M. Danger signals activating innate immunity in graft-versus-host disease. J Mol Med(Berl) 2011 Sep;89(9):833-45.
  • 14. Reddy P. Pathopysiology of acute graft versus host disease. Hematol Oncol 2003 Dec:21(4):149-61.
  • 15. Sung AD, Chao NJ. Acute graft-versus-host disease: Are we close to bringing the bench to the bedside? Best Pract Res Clin Haematol 2013 Sep;26(3):285-92.
  • 16. Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, et al. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011 Nov 3;118(18):5011-20.
  • 17. Socié G, Ritz J. Current issues in chronic graft-versus-host disease. Blood 2014 Jul 17;124(3):374-84.
  • 18. Sarantopoulos S, Ritz J. Aberrant B-cell homeostasis in chronic GVHD. Blood 2015 Mar 12;125(11):1703-7.
  • 19. Zeiser R, Blazar BR. Pathophysiology of chronic graft versus host disease and therapeutic targets. N Engl J Med 2017 Dec 28;377(26):2565-2579.
  • 20. Ghimire S, Weber D, Mavin E, Wang, XN, Dickinson, AM, Holler, E. Pathophysiology of GvHD and other HSCT-related major complications. Front Immunol 2017 Mar 20;8:79.
  • 21. Qayed M, Wang T, Hemmer MT, Spellman S, Arora M, Couriel D, et al. Influence of age on acute and chronic GVHD in children undergoing HLA-identical sibling bone marrow transplantation for acute leukemia: Implications for prophylaxis. Biol Blood MarrowTransplant 2018 Mar;24(3):521-8.
  • 22. Vignon M, Andreoli A, Dhédin N, Lebgline E, Masson E, Robin M, et al. Graft-versus-host disease in adolescents and young adults (15-24 years old) after allogeneic hematopoietic stem cell transplantation for acute leukemia in first complete remission. J Adolesc Young Adult Oncol 2017 Jun;6(2):299-306.
  • 23. Carlberg V, Simons E, Delano S, Huang JT. Pediatric Graft- Versus-Host Diease In: Cotliar JA, eds. Atlas of Graft-Versus-Host Diease: Approaches to Diagnosis and Treatment. Cham, 1st ed. Switzerland: Springer International Publishing AG, 2017:105-23.
  • 24. Gatza E, Reddy P, Choi SW. Prevention and treatment of acute graftversus- host disease in children, adolescents, and young adults. Biol Blood Marrow Transplant 2020 May;26(5):e101-e112.
  • 25. Hosseini E, Schwarer AP, Ghasemzadeh M. The impact of HLA-E polymorphisms in graft-versus-host disease following HLA-E matched allogeneic hematopoietic stem cell transplantation. Iran J Allergy Asthma Immunol 2012;11(1):15-21.
  • 26. Hosseini E, Schwarer AP, Ghasemzadeh M. Do human leukocyte antigen E polymorphisms influence graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation? Exp Hematol 2015 Mar;43(3):149-57.
  • 27. The IMGT/HLA Database; http://www.ebi.ac.uk/imgt/hla/stats. html Erişim tarihi: 27.03.2014
  • 28. Meyer D, Aguriar VRC, Bitarello BD, Brandt DYC, Nunes K. A genomic perspective on HLA evolution. Immunogenetics 2018 Jan;70(1):5-27.
  • 29. Edgerly CH, Weimer ET. The Past, present, and future of HLA typing in transplantation. Methods Mol Biol 2018;1802:1-10.
  • 30. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor recipient HLA matching contributest othe success of unrelated donor marrow transplantation. Blood 2007 Dec 15;110(13):4576-83.
  • 31. Touzeau C, Gagne K, Sebille V, Herry P, Chevallier P, Follea G, et al. Investigation of the impact of HLA-DPB1 matching status in 10/10 HLA matched unrelated hematopoietic stem cell transplantation: results of a French single center study. Hum Immunol 2012 Jul;73(7):711-4.
  • 32. Crocchiolo R, Zino E, Vago L, Oneto R, Bruno B, Pollichieni S, et al. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation. Blood 2009 Aug 13;114(7):1437-44.
  • 33. Rene C, Lozano C, Eliaou JF. Expression of classical HLA class I molecules: regulation and clinical impacts: Julia Bodmer award review 2015. HLA 2016 May;87(5):338-49.
  • 34. Summers C, Sheth VS, Bleakley M. Minor histocompatibility antigen-specific T cells. Front Pediatr 2020 Jun3;8:284.
  • 35. Roy DC, Perreault C. Major vs minor histocompatibility antigens. Blood 2017 Feb 9;129(6):664-6.
  • 36. Akatsuka Y, Warren EH, Gooley TA, Brickner AG, Lin MT, Hansen JA, et al. Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling. Br J Haematol 2003 Nov;123(4):671-5.
  • 37. McCarroll SA, Bradner JE, Turpeinen H, Volin L, Martin PJ, Chilewski SD, et al. Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease. Nat Genet 2009 Dec;41(12):1341-4.
  • 38. Martin PJ, Levine DM, Storer BE, Warren EH, Zheng X, Nelson SC et al. Genome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease. Blood 2017 Feb 9;129(6):791-8.
  • 39. Mohty M, Blaise D, Faucher C, Vey N, Bouabdallah R, Stoppa AM, et al. Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2005 Dec 15;106(13):4407-11.
  • 40. Henden AS, Hill GR. Cytokines in graft-versus-host disease. J Immunol 2015 May 15;194(10):4604-12.
  • 41. Kumar S, Mohammadpour H, Cao X. Targeting cytokines in GVHD therapy. J Immunol Res Ther 2017;2(1):90-9.
  • 42. Yi T, Chen Y, Wang L, Du G, Huang D, Zhao D, et al. Reciprocal differentiation and tissue- specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood 2009 Oct 1;114(14):3101-12.
  • 43. Hüber CM, Doisne JM, Colucci F. IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation. Eur J Immunol 2015 Jun;45(6):1727-35.
  • 44. Taylor PA, Panoskaltsis-Mortari A, Freeman GJ, Sharpe AH, Noelle RJ, Rudensky AY, et al. Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM). Blood 2005 Apr 15;105(8):3372-80.
  • 45. Zeiser R, Blazar BR. Acute graft versus host disease-biologic process, prevention and therapy. N Engl J Med 2017 Nov 30;377(22):2167- 79.
  • 46. Ijaz A, Khan AY, Malik SU, Faridi W, Fraz MA, Usman M, et al. Significant risk of graft-versus-host disease with exposure to checkpoint inhibitors before and after allogeneic transplantation. Biol Blood Marrow Transplant 2019 Jan;25(1):94-9.
  • 47. Haverkos BM, Abbott D, Hamadani M, Armand P, Flowers ME, Merryman E, et al. PD-1 blockade for relapsed lymphoma postallogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 2017 Jul 13;130(2):221-8.
There are 47 citations in total.

Details

Primary Language Turkish
Subjects Paediatrics
Journal Section Review
Authors

Demet Kıvanç 0000-0002-2451-5709

Fatma Savran Oğuz 0000-0002-6018-8936

Publication Date December 29, 2020
Published in Issue Year 2020 Volume: 20 Issue: 3

Cite

APA Kıvanç, D., & Oğuz, F. S. (2020). GvHH Patogenezi ve Biyolojisi. Çocuk Dergisi, 20(3), 115-119.
AMA Kıvanç D, Oğuz FS. GvHH Patogenezi ve Biyolojisi. Çocuk Dergisi. December 2020;20(3):115-119.
Chicago Kıvanç, Demet, and Fatma Savran Oğuz. “GvHH Patogenezi Ve Biyolojisi”. Çocuk Dergisi 20, no. 3 (December 2020): 115-19.
EndNote Kıvanç D, Oğuz FS (December 1, 2020) GvHH Patogenezi ve Biyolojisi. Çocuk Dergisi 20 3 115–119.
IEEE D. Kıvanç and F. S. Oğuz, “GvHH Patogenezi ve Biyolojisi”, Çocuk Dergisi, vol. 20, no. 3, pp. 115–119, 2020.
ISNAD Kıvanç, Demet - Oğuz, Fatma Savran. “GvHH Patogenezi Ve Biyolojisi”. Çocuk Dergisi 20/3 (December 2020), 115-119.
JAMA Kıvanç D, Oğuz FS. GvHH Patogenezi ve Biyolojisi. Çocuk Dergisi. 2020;20:115–119.
MLA Kıvanç, Demet and Fatma Savran Oğuz. “GvHH Patogenezi Ve Biyolojisi”. Çocuk Dergisi, vol. 20, no. 3, 2020, pp. 115-9.
Vancouver Kıvanç D, Oğuz FS. GvHH Patogenezi ve Biyolojisi. Çocuk Dergisi. 2020;20(3):115-9.