Time course of changes in iron metabolic and oxidative-antioxidative system parameters in patients with acute myeloid leukemia

Full Text

Abstract

AIM: To study an association between iron metabolism, free radical oxidation (FRO), and antioxidative system (AOS) in patients with acute myeloid leukemia (AML) during intensive chemotherapy/MATERIAL AND METHODS: AML patients (n=14) with a median age of 46 years received 7+3 courses (n=3) containing cytarabine ≥1 g/m2/introduction (n=8) and myeloablative conditioning regimen before hematopoietic stem cell transplantation (n=3). The concentrations of iron, ferritin, transferrin saturation (TFS), and malonic dialdehyde and the activity of superoxide dismutase (SOD), ceruloplasmin (CP), and catalase were investigated in their sera. The investigations were performed before and after chemotherapy and during hemopoietic recovery and rehospitalization/RESULTS: After therapy termination, there was a significant increase in TFS (6.8% vs 41.9%; p<0.0001), which gave way to its reduction during hemopoietic recovery (89.5% vs 96.8%; p=0.003). The activity of antioxidant enzymes was found to be altered at a time. That of catalase was enhanced throughout cytopenia (3.8 and 3.3 vs 5.7 conventional units (CU)/ml; р=0.028 and р=0.011). The lower activity of SOD (21.0 vs 41.0 CU/ml; p=0.018) and the higher activity of CP (1.1 vs 0.8 g/l) were ascertained when leukocyte count increased up to ≥1·109/l/CONCLUSION: After intensive cytostatic therapy, there was a phasic TFS increase accompanied by the compensatory change in AOS activity, which is aimed at neutralizing FRO products.

Full Text

Динамика показателей обмена железа и окислительно-антиокислительной системы у больных острыми миелоидными лейкозами. - Резюме. Цель исследования. Изучить сопряженность обмена железа, свободнорадикального окисления (СРО) и антиоксидантной системы (АОС) у больных острыми миелоидными лейкозами (ОМЛ) при проведении интенсивной химиотерапии. Материалы и методы. Больным ОМЛ (n=14) с медианой возраста 46 лет провели курсы "7+3" (n=3), содержащие цитарабин ≥1 г/м2/введение (n=8), и миелоаблативный режим кондиционирования до трансплантации гемопоэтических стволовых клеток (n=3). В сыворотке крови исследовали концентрацию железа, ферритина, насыщения трансферрина железом (НТЖ), малонового диальдегида (МДА) и активность супероксиддисмутазы (СОД), церулоплазмина (ЦП) и каталазы. Исследования выполняли до химиотерапии и после ее завершения, а также при восстановлении гемопоэза и повторной госпитализации. Результаты. После окончания терапии выявлено достоверное повышение НТЖ (6,8% против 41,9%; р<0,0001), которое сменялось снижением уровня НТЖ при восстановлении кроветворения (89,5% против 96,8%; р=0,003). Одновременно установлено изменение активности антиоксидантных ферментов. Активность каталазы была повышенной в течение всего периода цитопении (3,8 и 3,3 усл. ед. акт/мл против 5,7 усл. ед. акт/мл; р=0,028 и р=0,011). Снижение активности СОД (21,0 усл. ед. акт/мл против 41,0 усл. ед. акт/мл; р=0,018) и повышение активности ЦП (1,1 г/л против 0,8 г/л) выявлены в период увеличения количества лейкоцитов до ≥1·109/л. Заключение. После окончания интенсивной цитостатической терапии развивается фазовое повышение НТЖ, сопровождаемое компенсаторным изменением активности АОС, которое направлено на нейтрализацию продуктов СРО.
×

References

  1. Alessandrino E.P., Della Porta M.G., Bacigalupo A. et al. Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study. Haematologica 2010; 95: 476-484.
  2. Altes A., Remacha A.F., Sarda P. et al. Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis. Bone Marrow Transpl 2004; 34: 505-509.
  3. Armand P., Kim H.T., Cutler C.S. et al. Prognostic impact of elevated pretransplantation serum ferritin in patient undergoing myeloablative stem cell transplantation. Blood 2007; 109: 4586-4588.
  4. Kataoka K., Nannya Y., Hangaishi A. et al. Influence of pretransplantation serum ferritin on nonrelapse mortality after myeloablative and nonmyeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15: 195-204.
  5. Malcovati L., Della Porta M.G., Pascutto C. et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23: 7594-7603.
  6. Miceli M.H., Dong L., Grazziutti M.L. et al. Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients. Bone Marrow Transplant 2006; 37: 857-864.
  7. Pullarkat V., Blanchard S., Tegtmeier B. et al. Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2008; 42: 799-805.
  8. Maradei S.C., Maiolino A., de Azevedo A.M. et al. Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation. Blood 2009; 114: 1270-1275.
  9. Platzbecker U., Bornhauser M., Germing U. et al. Red blood cell transfusion dependence and outcome after allogeneic peripheral blood stem cell transplantation in patients with de novo myelodysplastic syndrome. Biol Blood Marrow Transplant 2008; 14: 1217-1225.
  10. Sanz G., Nomdedeu B., Such E. et al. Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Blood 2008; 112: 640.
  11. Kontoyiannis D.P., Chamilos G., Lewis R.E. et al. Increased bone marrow iron stores is an independent risk factor for invasive aspergillosis in patients with high-risk hematologic malignancies and recipients of allogeneic hematopoietic stem cell transplantation. Cancer 2007; 110: 1303-1306.
  12. Mattiuzzi G., Amin H.M., Kantarjian H. et al. Baseline serum ferritin predicts rate of infection in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome. Blood 2009; 114: Abstr. 1611.
  13. Bullen J., Rogers H.J., Salding P.B., Ward C.G. Iron and infection: the heart of matter. FEMS Immunol Med Microbiol 2005; 43: 325-330.
  14. Bullen J.J, Rogers H.J., Spalding P.B., Ward C.G. Natural resistance, iron and infection: a challenge for clinical medicine. J Med Microb 2006; 55: 251-258.
  15. Dreyfus F. The deleterious effects of iron overload in patients with myelodysplastic syndromes. Blood Rev 2008; 22 (Suppl. 2): S29-S34.
  16. Pullarkat V. Objectives of iron chelation therapy in myelodysplastic syndromes: more than meets the eye? Blood 2009; 114: 5251-5255.
  17. Evens A.M., Mehta J., Gordon L. Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress. Bone Marrow Transplant 2004; 34: 561-571.
  18. Ghoti H., Fibach E., Merkel D. et al. Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes. Haematologica 2010; 95: 1433-1434.
  19. Franchini M., Gandini G., Veneri D. et al. Efficacy and safety of phlebotomy to reduce transfusional iron overload in adult, long-term survivors of acute leukemia. Transfusion 2004; 44: 833-837.
  20. von Bonsdorff L., Sahlstedt L., Ebeling F. et al. Apotransferrin administration prevents growth of Staphylococcus epidermidis in serum of stem cell transplant patients by binding of free iron. FEMS Immunol Med Microbiol 2004; 40: 173-180.
  21. Parkkinen J., Sahlstedt L., von Bonsdorff L. et al. Effect of repeated apotransferrin administrations on serum iron parameters in patients undergoing myeloablative conditioning and allogeneic stem cell transplantation. Br J Haemat 2006; 135: 228-234
  22. Lee J.W., Kang H.J., Kim E.K. et al. Effect of iron overload and iron-chelating therapy on allogeneic hematopoietic SCT in children. Bone Marrow Transpl 2009; 44: 793-797.
  23. List A.F., Baer M.R., Steensma D. et al. Iron chelation with deferasirox (Exjade) improves iron burden in patients with myelodysplastic syndromes. Blood 2008; 112: Abstr. 634.
  24. Maertens J., Demuynck H., Verbeken E.K. et al. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transpl 1999; 24: 307-312.
  25. Андреева Л.И., Кожемякин Л.А, Кишкун А.А. Модификация метода определения перекиси липидов в тесте с тиобарбитуровой кислотой. Лаб дело 1988; 11: 41-43.
  26. Костюк В.А., Потапович А.И., Ковалев Ж.В. Простой и чувствительный метод определения активности супероксиддисмутазы, основанный на реакции окисления кверцитина. Вопр мед химии 1990; 2: 88-91.
  27. Королюк М.А., Иванова Л.И., Майорова И.Г. Токарева В.Е. Метод определения активности каталазы. Лаб дело 1998; 1: 16-18.
  28. Ravin H., Harvard M. Rapid test for hepato-lenticular degeneration. Lancet 1956; 1: 726-727.
  29. Burnett A., Hills R., Hunter A.E. et al. The addition of gemtuzumab ozogamicin to low dose ara-C improves remission rates but not survival: results of the UK LRF AML14 and NCRI AML16 "Pick a Winner" comparison. Blood 2010: 116: 18.
  30. Kantarjan H., O'Brian S., Cortes J. et al. Results of intensive chemotherapy in 988 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer 2006; 106: 1090-1098.
  31. Storey J.A., Connor R.F., Lewis Z.T. et al. The transplant iron score as a predictor of stem cell transplant survival. J Hematol Oncol 2009; 2: 44 doi: 10.1186/1756-8722-2-44
  32. Sahlstedt L., Ebeling F., von Bonsdorf L. et al. Non-transferrin-bound iron during allogeneic stem cell transplantation. Br J Haemat 2001; 113: 836-838.
  33. Bozuave G.N., Buser A.S., Gerull S. et al. Prognostic impact of different iron parameters in patients undergoing allogeneic hematopoietic stem cell transplantation. Blood 2010; 116: 168.
  34. Bradley S.J., Gosriwitana I., Srichairatanakool S. et al. Non-transferrin-bound iron induced by myeloablative chemotherapy. Br J Haemat 1997; 99: 337-343.
  35. Sahlstedt L., von Bonsdorff L., Ebeling F. et al. Non-transferrin-bound iron in haematological patients during chemotherapy and conditioning for autologous stem cell transplantation. Eur J Haematol 2009; 83: 455-459.

Statistics

Views

Abstract: 152

Article Metrics

Metrics Loading ...

Refbacks

  • There are currently no refbacks.

Copyright (c) 2020 Gritsaev S.V., Shikhbabaeva D.I., Rybakova L.P., Sergeev A.N., Kapustin S.I., Abdulkadyrov K.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies