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Role of Uric Acid Levels as a Prognostic Indicator in Allogeneic Hematopoietic Stem Cell Transplantation: Insights from a Single-Center Study

Year 2024, , 121 - 128, 29.06.2024

Neslihan Mandacı Şanlı , Muzaffer Keklik , Ali Ünal

https://doi.org/10.7197/cmj.1428410

Abstract

Uric acid (UA) acts as a richly available water-soluble antioxidant, contributing to approximately two-thirds of the overall free-radical-scavenging activity in human serum. It is discharged from damaged cells during the preparation for allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study assessed how pretransplantation uric acid levels influence survival and mortality in allo-HSCT patients. In a retrospective analysis of 267 patients with hematologic diseases who underwent allo-HSCT, uric acid levels were documented on the day of allo-HSCT (day 0). Patients were divided into two cohorts based on their pretransplant uric acid levels: those at or below 4.4 mg/dL and those above 4.4 mg/dL. Among them, 153 (57.3%) were male, and 114 (42.7%) were female, with a median age of 31 years (ranging from 13 to 66). Those with serum uric acid levels of 4.4 mg/dL or lower exhibited notably poorer overall survival (OS) and disease-free survival (DFS) compared to those surpassing 4.4 mg/dL (p=0.032 and p=0.045, respectively). Our findings indicate an interrelation between low pretransplant serum uric acid levels and reduced survival rates in allo-HSCT patients. Further exploration into potential mechanisms, such as compromised antioxidative capacity in hypouricemia, may establish uric acid as a promising prognostic marker in allo-HSCT.

Keywords

uric acid allogeneic hematopoeitic stem cell transplantation survival prognosis

References

  • Arcangelo L, Margherita N, Francesca M, Raffaele LR, Emanuela T. Hematopoietic Stem Cell Transplantation: A Bioethical Lens. Stem Cells International 2017;2017: 1286246.
  • Lu Z, Shanquan C, Panxin Y, Hongcui C, Lanjuan L. The role of mesenchymal stem cells in hematopoietic stem cell transplantation: prevention and treatment of graf-versus host disease. Stem Cell Research & Therapy. 2019;21;10(1):182.
  • Yao-Chung L, Sheng-Hsuan C, Nai-Wen F, et al. Prognostic Factors on the Graft- versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation. Stem Cells International 2016. 5143071.
  • John R W, Jack H, John W H. Wingard JR, Hsu JH, Heimenz JW. Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Infect. Dis. Clin. North. Am. 2010;24(2):257-72. https://doi:10.1016/j.idc.2010.01.010
  • Ugur S, Selami KT, Pinar AA, Atilla E, Taner D. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. Journal of Infection and Chemotherapy 2016;22(8):505-14. https://doi: 10.1016/j.jiac.2016.05.006.
  • Navneet SM. Long Term Complications After Hematopoietic Cell Transplantation. Hematol Oncol Stem Cell Ther 2017;10(4):220-27. https://doi:10.1016/j.hemonc.2017.05.009
  • Akifumi K, Yusuke N, Yasuka M. et al. Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis. Mediators of Inflammation 2016;2016:8603134. https://doi: 10.1155/ 2016/8603164
  • Cristine E B, Joshua M H. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. Journal of Physiology 2004;16;555:589-606. https://doi:10.1113/jphysiol.2003. 055913
  • Buruce NA, Richard C, Elizabeth S, Paul H. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proceedings of the National Academy of Sciences of the United States of America 1981;78(11):6858-62.
  • Pu F, Xinyuan L, Jin Jun L, Hong W and Xiao-F Yang. A Double-edged Sword: Uric Acid and Neurological Disorders. Brain Disord Ther 2013;2:109. https://doi:10.4172/2168-975X.1000109
  • Jee Wook K, Min Soo B, Dahyun Y. Serum uric acid Alzheimer-related Brain Changes and Cognitive Impairment. Front Aging Neurosci. 2020;12:160. https://doi: 10.3389/fnagi.2020.00160.
  • Bo L, Yuefei S, Kaiwen X, et al. Serum uric acid levels in patients with multiple sclerosis:ameta-analysis. Neurological Research. 2012;34(2):163-171. https://doi: 10.1179/1743132811Y.0000000074
  • Fereshteh A, Mohammadali B, Maryam A, Arash Z. Serum uric acid level in patients with relapsing- remitting multiple sclerosis. Journal of Clinical Neuroscience 2013;20(5):676-78. https://doi: 10.1016/j.jocn.2012.05.054
  • Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress. Journal of the Neurological Sciences 2009;285:95–9. https://doi:
  • Sabrina P, May Z, Alejandro QZ et al. Uric acid levels predict survival in men with amyotrophic lateral sclerosis. Journal of Neurology 2012;259:1923-28. https://doi:10.1007/s00415-012-6440-7
  • Benjamin NO, Olga B, Lutz U, Igor WB, Olaf P. Association between low uric acid levels and acute graft versus host disease. Ann Hematol 2015;94(1):139-44. https://doi: 10.1007/s00277-014-2180-3
  • Katayoon G, Sayeh P, Mohammad HK, et al. The role of serum uric acid in the prediction of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. J Clin Lab Anal 2020;34(7):e23271. https://doi: 10.1002/ jcla.23271.
  • Philippe A, Christopher JG, Corey C, et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012;120(4):905-13. https://doi:10.1182/blood-2012-03-418202
  • Yasuhito N, Keisuke K, Akira H, et al. The negative impact of female donor/male recipient combination in allogeneic hematopoietic stem cell transplantation depends on disease risk. Transpl Int 2011;24(5):469-76. https://doi:10.1111 /j.1432-2277.2011.01229.x.
  • Przepiorka D, Weisdorf D, Martin P, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995;15(6):825-28. https://doi:
  • Stephanie JL , Georgia V, Mary EDF. Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003;9(4):215-33. https://doi:10.1053/bbmt.2003.50026.
  • Alon A, Vivian ED. Influence of serum uric acid levels on prognosis and survival in amyotrophic lateral sclerosis: a meta-analysis. Journal of Neurology 2014;261(6):1133-38. https://doi: 10.1007/s00415-014-7331-x.
  • Peggy A, Karl K, and Michael PM. The Relationship between Uric Acid Levels and Huntington’s Disease Progression. Mov Disord.2010;25(2):22428. https://doi:10.1002/mds.22907.
  • Mustafa C, Yusuf Y, Mehmet EK, et al. Altered levels of homocysteine and serum natural antioxidants links oxidative damage to Alzheimer's disease. J Alzheimers Dis 2013;33:1051-58. https://doi:10.3233/JAD-2012-121630.
  • Warıng WS, Convery A, Mıshra V, et al. Uric acid reduces exercise-induced oxidative stress in healthy adults. Clinical Science 2003;105:425-30. https://doi:10.1042/CS20030149.
  • Olaf P, Christophe P, Steffie van der Werf et al. Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation a prospective, non-interventional study of the EBMT Transplant Complication Working Party. Haematologica. 2020;105(7):1977-83. https://doi:10.3324/haematol.2019.228668.
  • Yuri YS, Richard JJ. Uric acid: The oxidant- antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 2008;27(6):608-9. https://doi:10.1080/15257770802138558.

Allojenik Hematopoetik Kök Hücre Nakli’ nde Ürik Asit Seviyesinin Prognostik Bir Belirteç Olarak Rolü: Tek Merkez Deneyimi

Year 2024, , 121 - 128, 29.06.2024

Neslihan Mandacı Şanlı , Muzaffer Keklik , Ali Ünal

https://doi.org/10.7197/cmj.1428410

Abstract

Ürik asit (UA) suda çözünebilen zengin bir antioksidan olarak görevi görür ve insan serumundaki toplam serbest radikal süpürücü aktivitenin yaklaşık üçte ikisine katkıda bulunur. Allojeneik hematopoetik kök hücre nakli (allo-HKHN) için hazırlık sırasında hasarlı hücrelerden atılır. Bu çalışmada, allo-HKHN hastalarında nakil öncesi ürik asit düzeylerinin sağkalım ve mortaliteyi nasıl etkilediği değerlendirilmiştir. Hematolojik hastalığı olan ve allo-HKHN yapılan 267 hastanın retrospektif analizinde, ürik asit düzeyleri allo-HKHN gününde (0. gün) belgelenmiştir. Hastalar nakil öncesi ürik asit düzeylerine göre iki gruba ayrılmıştır: 4,4 mg/dL veya altında olanlar ve 4,4 mg/dL'nin üzerinde olanlar. Bunların 153 'ü (%57,3) erkek, 114' ü (%42,7) kadındı ve ortanca yaşları 31'di (13 ile 66 arasında değişiyordu). Serum ürik asit düzeyleri 4,4 mg/dL veya altında olanlar, 4,4 mg/dL'yi aşanlara kıyasla belirgin şekilde daha kötü genel sağkalım (OS) ve hastalıksız sağkalım (DFS) sergilemiştir (sırasıyla p=0,032 ve p=0,045). Bulgularımız, allo-HKHN hastalarında düşük pretransplant serum ürik asit düzeyleri ile azalmış sağkalım oranları arasında bir ilişki olduğunu göstermektedir. Hipoürisemide bozulmuş antioksidatif kapasite gibi potansiyel mekanizmaların daha fazla araştırılması, ürik asidin allo-HKHN' nde umut verici bir prognostik belirteç olmasını sağlayabilir.

Keywords

Ürik asit Allojenik Hematopoietik Kök Hücre Nakli Sağkalım Prognoz

References

  • Arcangelo L, Margherita N, Francesca M, Raffaele LR, Emanuela T. Hematopoietic Stem Cell Transplantation: A Bioethical Lens. Stem Cells International 2017;2017: 1286246.
  • Lu Z, Shanquan C, Panxin Y, Hongcui C, Lanjuan L. The role of mesenchymal stem cells in hematopoietic stem cell transplantation: prevention and treatment of graf-versus host disease. Stem Cell Research & Therapy. 2019;21;10(1):182.
  • Yao-Chung L, Sheng-Hsuan C, Nai-Wen F, et al. Prognostic Factors on the Graft- versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation. Stem Cells International 2016. 5143071.
  • John R W, Jack H, John W H. Wingard JR, Hsu JH, Heimenz JW. Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Infect. Dis. Clin. North. Am. 2010;24(2):257-72. https://doi:10.1016/j.idc.2010.01.010
  • Ugur S, Selami KT, Pinar AA, Atilla E, Taner D. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. Journal of Infection and Chemotherapy 2016;22(8):505-14. https://doi: 10.1016/j.jiac.2016.05.006.
  • Navneet SM. Long Term Complications After Hematopoietic Cell Transplantation. Hematol Oncol Stem Cell Ther 2017;10(4):220-27. https://doi:10.1016/j.hemonc.2017.05.009
  • Akifumi K, Yusuke N, Yasuka M. et al. Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis. Mediators of Inflammation 2016;2016:8603134. https://doi: 10.1155/ 2016/8603164
  • Cristine E B, Joshua M H. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. Journal of Physiology 2004;16;555:589-606. https://doi:10.1113/jphysiol.2003. 055913
  • Buruce NA, Richard C, Elizabeth S, Paul H. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proceedings of the National Academy of Sciences of the United States of America 1981;78(11):6858-62.
  • Pu F, Xinyuan L, Jin Jun L, Hong W and Xiao-F Yang. A Double-edged Sword: Uric Acid and Neurological Disorders. Brain Disord Ther 2013;2:109. https://doi:10.4172/2168-975X.1000109
  • Jee Wook K, Min Soo B, Dahyun Y. Serum uric acid Alzheimer-related Brain Changes and Cognitive Impairment. Front Aging Neurosci. 2020;12:160. https://doi: 10.3389/fnagi.2020.00160.
  • Bo L, Yuefei S, Kaiwen X, et al. Serum uric acid levels in patients with multiple sclerosis:ameta-analysis. Neurological Research. 2012;34(2):163-171. https://doi: 10.1179/1743132811Y.0000000074
  • Fereshteh A, Mohammadali B, Maryam A, Arash Z. Serum uric acid level in patients with relapsing- remitting multiple sclerosis. Journal of Clinical Neuroscience 2013;20(5):676-78. https://doi: 10.1016/j.jocn.2012.05.054
  • Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress. Journal of the Neurological Sciences 2009;285:95–9. https://doi:
  • Sabrina P, May Z, Alejandro QZ et al. Uric acid levels predict survival in men with amyotrophic lateral sclerosis. Journal of Neurology 2012;259:1923-28. https://doi:10.1007/s00415-012-6440-7
  • Benjamin NO, Olga B, Lutz U, Igor WB, Olaf P. Association between low uric acid levels and acute graft versus host disease. Ann Hematol 2015;94(1):139-44. https://doi: 10.1007/s00277-014-2180-3
  • Katayoon G, Sayeh P, Mohammad HK, et al. The role of serum uric acid in the prediction of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. J Clin Lab Anal 2020;34(7):e23271. https://doi: 10.1002/ jcla.23271.
  • Philippe A, Christopher JG, Corey C, et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012;120(4):905-13. https://doi:10.1182/blood-2012-03-418202
  • Yasuhito N, Keisuke K, Akira H, et al. The negative impact of female donor/male recipient combination in allogeneic hematopoietic stem cell transplantation depends on disease risk. Transpl Int 2011;24(5):469-76. https://doi:10.1111 /j.1432-2277.2011.01229.x.
  • Przepiorka D, Weisdorf D, Martin P, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995;15(6):825-28. https://doi:
  • Stephanie JL , Georgia V, Mary EDF. Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003;9(4):215-33. https://doi:10.1053/bbmt.2003.50026.
  • Alon A, Vivian ED. Influence of serum uric acid levels on prognosis and survival in amyotrophic lateral sclerosis: a meta-analysis. Journal of Neurology 2014;261(6):1133-38. https://doi: 10.1007/s00415-014-7331-x.
  • Peggy A, Karl K, and Michael PM. The Relationship between Uric Acid Levels and Huntington’s Disease Progression. Mov Disord.2010;25(2):22428. https://doi:10.1002/mds.22907.
  • Mustafa C, Yusuf Y, Mehmet EK, et al. Altered levels of homocysteine and serum natural antioxidants links oxidative damage to Alzheimer's disease. J Alzheimers Dis 2013;33:1051-58. https://doi:10.3233/JAD-2012-121630.
  • Warıng WS, Convery A, Mıshra V, et al. Uric acid reduces exercise-induced oxidative stress in healthy adults. Clinical Science 2003;105:425-30. https://doi:10.1042/CS20030149.
  • Olaf P, Christophe P, Steffie van der Werf et al. Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation a prospective, non-interventional study of the EBMT Transplant Complication Working Party. Haematologica. 2020;105(7):1977-83. https://doi:10.3324/haematol.2019.228668.
  • Yuri YS, Richard JJ. Uric acid: The oxidant- antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 2008;27(6):608-9. https://doi:10.1080/15257770802138558.
There are 27 citations in total.

Details

Primary Language English
Subjects Medical Education
Journal Section Research Article
Authors

Neslihan Mandacı Şanlı 0000-0002-6298-9884

Muzaffer Keklik 0000-0002-6426-5249

Ali Ünal 0000-0001-7011-3412

Publication Date June 29, 2024
Submission Date January 30, 2024
Acceptance Date June 9, 2024
Published in Issue Year 2024

Cite

AMA Mandacı Şanlı N, Keklik M, Ünal A. Role of Uric Acid Levels as a Prognostic Indicator in Allogeneic Hematopoietic Stem Cell Transplantation: Insights from a Single-Center Study. CMJ. June 2024;46(2):121-128. doi:10.7197/cmj.1428410