Metabolismo do Ferro, Biomarcadores, Sobrecarga de Ferro e Quelação: Recomendações em Síndromes Mielodisplásicas

Autores

DOI:

https://doi.org/10.24950/rspmi/Revisao/225/18/3/2019

Palavras-chave:

Consenso, Quelantes de Ferro, Síndromes Mielodisplásicas, Sobrecarga de Ferro, Terapia por Quelação, Transfusão de Sangue

Resumo

As síndromes mielodisplásicas (SMD) são um grupo heterogéneo de neoplasias mielóides caracterizadas por citopenias decorrentes de hematopoiese ineficaz e por risco
aumentado de progressão para leucemia mieloide aguda.
Afetam 5/100 000 pessoas por ano em Portugal, dos quais
mais de 60% se tornará dependente de transfusões ao longo do curso de doença. As citopenias podem levar a uma
morbilidade significativa, sendo a sua gestão um dos pontos-chave para a melhoria da qualidade de vida destes
doentes. Este documento compila o resultado do debate
promovido pelo Anemia Working Group Portugal com peritos
reconhecidos sobre a abordagem de suporte dos doentes
com SMD de risco mais baixo, focando os efeitos a médio
e longo prazo das transfusões recorrentes e da sobrecarga
de ferro. Para o diagnóstico das SMD, recomenda-se a aplicação da classificação da Organização Mundial de Saúde
2016. O score International Prognosis Scoring System continua a ser a referência para definição de prognóstico e estratégia terapêutica. A terapêutica de suporte é um pilar fundamental do tratamento dos doentes em qualquer estádio
da sua doença e inclui antibióticos, transfusão de concentrado eritrocitário e plaquetas, fatores de crescimento hematopoiético, agentes antifibrinolíticos e terapêutica quelante.
Em doentes transfundidos com ≥ 20 unidades de concentrado eritrocitário ou com ferritina sérica ≥1 000 ng/mL, deve-se
considerar terapêutica com quelantes de ferro. Os doentes
candidatos a terapêutica quelante devem fazer ressonância
magnética ao fígado e pâncreas com periodicidade semestral ou anual. As opções terapêuticas devem ter em conta as
características da doença e a qualidade de vida do doente,
de acordo com as linhas orientadoras internacionais.

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Referências

Malcovati L, Hellström-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122:2943-64. doi:10.1182/blood-2013-03-492884

Greenberg PL, Stone RM, Al-Kali A, Barta SK, Bejar R, Bennett JM, et al. Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15:60-87.

Fenaux P, Haase D, Sanz GF, Santini V, Buske C, ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii57-69. doi: 10.1093/annonc/mdu180.

Bowen D, Culligan D, Jowitt S, Kelsey S, Mufti G, Oscier D, et al. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol. 2003;120:187-200. doi:10.1046/j.1365-2141.2003.03907.x

ROR Centro. Registo Oncológico Nacional 2008. Coimbra: RORC; 2008.

Wells RA, Leber B, Buckstein R, Lipton JH, Hasegawa W, Grewal K, et al. Iron overload in myelodysplastic syndromes: a Canadian consensus guideline. Leuk Res. 2008;32:1338-53. doi:10.1016/j.leukres.2008.02.021

Killick SB, Carter C, Culligan D, Dalley C, Das-Gupta E, Drummond M, et al. Guidelines for the diagnosis and management of adult myelodysplastic syndromes. Br J Haematol. 2014;164:503-25. doi:10.1111/bjh.12694

Onida F, Barosi G, Leone G, Malcovati L, Morra E, Santini V, et al. Management recommendations for chronic myelomonocytic leukemia: consensus statements from the SIE, SIES, GITMO groups. Haematologica. 2013;98:1344-52. doi:10.3324/haematol.2013.084020

Bennett JM. Consensus statement on iron overload in myelodysplastic syndromes. Am J Hematol. 2008;83:858-61. doi:10.1002/ajh.21269

Deeg HJ, Spaulding E, Shulman HM. Iron overload, hematopoietic cell transplantation, and graft-versus-host disease. Leuk Lymphoma. 2009;50:1566-72.

Platzbecker U, Bornhäuser M, Germing U, Stumpf J, Scott BL, Kröger N, et al. Red blood cell transfusion dependence and outcome after allogeneic peripheral blood stem cell transplantation in patients with de novo myelodysplastic syndrome (MDS). Biol Blood Marrow Transplant. 2008;14:1217-25. doi:10.1016/j.bbmt.2008.08.006

Hellström-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I, et al. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120:1037-46. http:// www.ncbi.nlm.nih.gov/pubmed/12648074.

Erickson-Miller CL, Kirchner J, Aivado M, May R, Payne P, Chadderton A. Reduced proliferation of non-megakaryocytic acute myelogenous leukemia and other leukemia and lymphoma cell lines in response to eltrombopag. Leuk Res. 2010;34:1224-31. doi:10.1016/j.leukres.2010.02.005

Kalota A, Gewirtz AM. A prototype nonpeptidyl, hydrazone class, thrombopoietin receptor agonist, SB-559457, is toxic to primary human myeloid leukemia cells. Blood. 2010;115:89-93. doi:10.1182/blood-2009-06-227751

Roth M, Will B, Simkin G, Narayanagari S, Barreyro L, Bartholdy B, et al. Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood. 2012;120:386-94. doi:10.1182/blood-2011-12-399667

Sugita M, Kalota A, Gewirtz AM, Carroll M. Eltrombopag inhibition of acute myeloid leukemia cell survival does not depend on c-Mpl expression. Leukemia. 2013;27:1207-10. doi:10.1038/leu.2012.310

Santini V, Girelli D, Sanna A, Martinelli N, Duca L, Campostrini N, et al. Hepcidin levels and their determinants in different types of myelodysplastic syndromes. PLoS One. 2011;6:e23109. doi:10.1371/journal.pone.0023109

Steensma D, Gattermann N. When is iron overload deleterious, and when and how should iron chelation therapy be administered in myelodysplastic syndromes? Best Pract Res Clin Haematol. 2013;26:431.

Cazzola M, Malcovati L. Myelodysplastic syndromes — coping with ineffective hematopoiesis. N Engl J Med. 2005;352:536. doi:10.1056/NEJMp048266

Suzuki T, Tomonaga M, Miyazaki Y, Nakao S, Ohyashiki K, Matsumura I, et al. Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes. Int J Hematol. 2008;88:30-5. doi:10.1007/s12185-008-0119-y

Lyons R, Marek B, Paley C, Esposito J, McNamara K, Richards PD, et al. Relationship between chelation and clinical outcomes in lower-risk patients with myelodysplastic syndrome (MDS): registry analysis at 5 years. Blood. 2014;124:1350.

Remacha ÁF, Arrizabalaga B, Villegas A, Durán MS, Hermosín L, de Paz R, et al. Evolution of iron overload in patients with low-risk myelodysplastic syndrome: iron chelation therapy and organ complications. Ann Hematol. 2015;94:779-87. doi:10.1007/s00277-014-2274-y

Coffey R, Ganz T. Erythroferrone : An erythroid regulator of hepcidin and iron metabolism. HemaSphere. 2018;2.

Pullarkat V, Blanchard S, Tegtmeier B, Dagis A, Patane K, Ito J, et al. Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2008;42:799-805. doi:10.1038/bmt.2008.262

Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol. 2005;18:277-87. doi:10.1016/j. beha.2004.10.003

Porter JB, de Witte T, Cappellini MD, Gattermann N. New insights into transfusion-related iron toxicity: Implications for the oncologist. Crit Rev Oncol Hematol. 2016;99:261-71. doi:10.1016/j.critrevonc.2015.11.017

KDOQI, National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis. 2006;47(5 Suppl 3):S11-145. doi:10.1053/j.ajkd.2006.03.010

Brugnara C, Zurakowski D, DiCanzio J, Boyd T, Platt O. Reticulocyte hemoglobin content to diagnose iron deficiency in children. JAMA. 1999;281:2225-30.

Ullrich C, Wu A, Armsby C, Rieber S, Wingerter S, Brugnara C,et al. Screening healthy infants for iron deficiency using reticulocyte hemoglobin content. JAMA. 2005;294:924-30. doi:10.1001/jama.294.8.924

Ribeiro-Alves MA, Gordan PA. Diagnosis of anemia in patients with chronic kidney disease. J Bras Nefrol. 2014;36. doi:10.5935/0101-2800.2014S003

Wians FH, Urban JE, Keffer JH, Kroft SH. Discriminating between iron deficiency anemia and anemia of chronic disease using traditional indices of iron status vs transferrin receptor concentration. Am J Clin Pathol. 2001;115:112- 8. doi:10.1309/6L34-V3AR-DW39-DH30

Wood JC. Guidelines for quantifying iron overload. Hematol Am Soc Hematol Educ Progr. 2014;2014:210-15. doi:10.1182/asheducation-2014.1.210

Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J. 2000;140:98-104. doi:10.1067/mhj.2000.106646

Brandão M, Oliveira JC, Bravo F, Reis J, Garrido I, Porto G. The soluble transferrin receptor as a marker of iron homeostasis in normal subjects and in HFE- -related hemochromatosis. Haematologica. 2005;90:31-37.

Thurnham DI, Northrop-Clewes CA. Inflammation and biomarkers of micronutrient status. Curr Opin Clin Nutr Metab Care. 2016;19:458-63. doi:10.1097/ MCO.0000000000000323

Porto G, Vicente C, Fraga J, da Silva BM, de Sousa M. Importance of establishing appropriate local reference values for the screening of hemochromatosis: a study of three different control populations and 136 hemochromatosis family members. Hemochromatosis Clinical and Research Group. J Lab Clin Med. 1992;119:295-305.

Piga A, Longo F, Duca L, Roggero S, Vinciguerra T, Calabrese R, et al. High nontransferrin bound iron levels and heart disease in thalassemia major. Am J Hematol. 2009;84:29-33. doi:10.1002/ajh.21317

Gandon Y, Olivié D, Guyader D, Aubé C, Oberti F, Sebille V, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004;363:357-62. doi:10.1016/S0140-6736(04)15436-6

Alústiza Echeverría JM, Castiella A, Emparanza JI. Quantification of iron concentration in the liver by MRI. Insights Imaging. 2012;3:173-80. doi:10.1007/ s13244-011-0132-1

Rowe JW, Wands JR, Mezey E, Waterbury LA, Wright JR, Tobin J, et al. Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred. Medicine. 1977;56:197-211.

Schmid M. Iron chelation therapy in MDS: what have we learnt recently? Blood Rev. 2009;23 :S21-5. doi:10.1016/S0268-960X(09)70006-2

Gattermann N. Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Int J Hematol. 2008;88(1):24-9. doi:10.1007/s12185-008-0118-z

Pullarkat V. Objectives of iron chelation therapy in myelodysplastic syndromes: more than meets the eye? Blood. 2009;114:5251-5. doi:10.1182/ blood-2009-07-234062

Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89:1187-93. http://www.ncbi.nlm.nih.gov/pubmed/15477202.

Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med. 1994;331:567-73. doi:10.1056/ NEJM199409013310902

Langemeijer S, De Swart L, Yu G. Impact of Treatment with Iron Chelators in Lower-Risk MDS Patients Participating in the European Leukemianet MDS (EUMDS) Registry. Blood. 2016;128:3186 LP-3186..

Goldberg SL. Novel treatment options for transfusional iron overload in patients with myelodysplastic syndromes. Leuk Res. 2007;31 Suppl 3:S16-22. doi:10.1016/S0145-2126(07)70462-9

Taher A, El-Beshlawy A, Elalfy MS, Al Zir K, Daar S, Habr D, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with beta-thalassaemia: the ESCALATOR study. Eur J Haematol. 2009;82:458-65. doi:10.1111/j.1600-0609.2009.01228.x

Gattermann N, Finelli C, Porta M Della, Fenaux P, Ganser A, Guerci-Bresler A, et al. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study. Leuk Res. 2010;34:1143-50. doi:10.1016/j.leukres.2010.03.009

Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, et al. Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major. Haematologica. 2012;97:842-8. doi:10.3324/haematol.2011.049957

Nolte F, Höchsmann B, Giagounidis A, Lübbert M, Platzbecker U, Haase D, et al. Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral Deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload. Ann Hematol. 2013;92:191-8. doi:10.1007/s00277-012-1594-z

List AF, Baer MR, Steensma D. Iron chelation with deferasirox (Exjade) improves iron burden in patients with myelodysplastic syndromes (MDS). Blood. 2008;112:634 LP-634.

Parmar A, Leitch HA, Wells RA, et al. Iron Chelation Is Associated with Improved Survival Adjusting for Disease and Patient Related Characteristics in Low/ Int-1 Risk MDS at the Time of First Transfusion Dependence: A MDS-CAN Study. Blood. 2015;126:1701 LP-1701.

Neukirchen J, Fox F, Kündgen A, Nachtkamp K, Strupp C, Haas R, et al. Improved survival in MDS patients receiving iron chelation therapy – A matched pair analysis of 188 patients from the Düsseldorf MDS registry. Leuk Res. 2012;36:1067-70. doi:10.1016/j.leukres.2012.04.006

Gattermann N, Schmid M, Della Porta M. Efficacy and Safety of Deferasirox (Exjade®) during 1 Year of Treatment in Transfusion-Dependent Patients with Myelodysplastic Syndromes: Results from EPIC Trial. Blood. 2008;:633.

Taher AT, Musallam KM, Inati A. Iron overload: consequences, assessment, and monitoring. Hemoglobin. 2009;33 Suppl 1:S46-57. doi:10.3109/03630260903346676

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Publicado

20-09-2019

Como Citar

1.
Brilhante D, Aldeia C, de Fátima Ferreira M, Afonso C, Rodrigues S, Ferreira J, Rey C, Sousa-Mendes D, Santos A, José Teles M, Cortez J, Robalo Nunes A. Metabolismo do Ferro, Biomarcadores, Sobrecarga de Ferro e Quelação: Recomendações em Síndromes Mielodisplásicas. RPMI [Internet]. 20 de Setembro de 2019 [citado 9 de Outubro de 2024];26(3):223-31. Disponível em: https://revista.spmi.pt/index.php/rpmi/article/view/415

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