NCCN Task Force: Transfusion and Iron Overload in Patients With Myelodysplastic Syndromes

Authors:
Peter L. Greenberg
Search for other papers by Peter L. Greenberg in
Current site
Google Scholar
PubMed Close
 MD
,
Cynthia K. Rigsby
Search for other papers by Cynthia K. Rigsby in
Current site
Google Scholar
PubMed Close
 MD
,
Richard M. Stone
Search for other papers by Richard M. Stone in
Current site
Google Scholar
PubMed Close
 MD
,
H. Joachim Deeg
Search for other papers by H. Joachim Deeg in
Current site
Google Scholar
PubMed Close
 MD
,
Steven D. Gore
Search for other papers by Steven D. Gore in
Current site
Google Scholar
PubMed Close
 MD
,
Michael M. Millenson
Search for other papers by Michael M. Millenson in
Current site
Google Scholar
PubMed Close
 MD
,
Stephen D. Nimer
Search for other papers by Stephen D. Nimer in
Current site
Google Scholar
PubMed Close
 MD
,
Margaret R. O'Donnell
Search for other papers by Margaret R. O'Donnell in
Current site
Google Scholar
PubMed Close
 MD
,
Paul J. Shami
Search for other papers by Paul J. Shami in
Current site
Google Scholar
PubMed Close
 MD
, and
Rashmi Kumar
Search for other papers by Rashmi Kumar in
Current site
Google Scholar
PubMed Close
 PhD
Volume/Issue:
Volume 7: Issue Suppl_9
Online Publication Date:
Dec 2009
DOI:
https://doi.org/10.6004/jnccn.2009.0082
Restricted access

The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force to critically review the evidence for iron chelation and the rationale for treatment of transfusional iron overload in patients with myelodysplastic syndromes (MDS). The task force was charged with addressing issues related to tissue iron toxicity; the role of MRI in assessing iron overload; the rationale and role of treating transfusional iron overload in patients with MDS; and the impact of iron overload on bone marrow transplantation. This report summarizes the background data and ensuing discussion from the NCCN Task Force meeting on transfusional iron overload in MDS.

  • Collapse
  • Expand
  • 1

    Greenberg P. The role of hemopoietic growth factors in the treatment of myelodysplastic syndromes. Int J Ped Hem-Onc 1997;4:231–238.

  • 2

    Greenberg P, Attar E, Battiwalla M et al.. NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes, version 2.2010. Available at: http://www.nccn.org. Accessed December 11, 2009.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Zurlo MG, De Stefano P, Borgna-Pignatti C et al.. Survival and causes of death in thalassaemia major. Lancet 1989;2:27–30.

  • 4

    Hershko CM, Link GM, Konijn AM, Cabantchik ZI. Iron chelation therapy. Curr Hematol Rep 2005;4:110–116.

  • 5

    Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89:739–761.

  • 6

    Malcovati L. Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res 2007;31(Suppl 3):S2–6.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Andrews NC. Iron homeostasis: insights from genetics and animal models. Nat Rev Genet 2000;1:208–217.

  • 8

    Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci 1998;850:191–201.

  • 9

    Cortelezzi A, Cattaneo C, Cristiani S et al.. Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis? Hematol J 2000;1:153–158.

  • 10

    Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 2005;18:277–287.

  • 11

    Esposito BP, Breuer W, Sirankapracha P et al.. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 2003;102:2670–2677.

  • 12

    Nemeth E, Tuttle MS, Powelson J et al.. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090–2093.

  • 13

    Rivera S, Liu L, Nemeth E et al.. Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia. Blood 2005;105:1797–1802.

  • 14

    Gattermann N. Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Leuk Res 2007;31(Suppl 3):S10–15.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Winder A, Lefkowitz R, Ghoti H et al.. Urinary hepcidin excretion in patients with myelodysplastic syndrome and myelofibrosis. Br J Haematol 2008;142:669–671.

  • 16

    Origa R, Galanello R, Ganz T et al.. Liver iron concentrations and urinary hepcidin in {beta}-thalassemia. Haematologica 2007;92:583–588.

  • 17

    Pippard MJ, Callender ST, Warner GT, Weatherall DJ. Iron absorption and loading in beta-thalassaemia intermedia. Lancet 1979;2:819–821.

  • 18

    Anderson LJ, Holden S, Davis B et al.. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001;22:2171–2179.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Wood JC, Enriquez C, Ghugre N et al.. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005;106:1460–1465.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Wood JC, Otto-Duessel M, Aguilar M et al.. Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation 2005;112:535–543.

  • 21

    Wood JC, Enriquez C, Ghugre N et al.. Physiology and pathophysiology of iron cardiomyopathy in thalassemia. Ann N Y Acad Sci 2005;1054:386–395.

  • 22

    Chacko J, Pennell DJ, Tanner MA et al.. Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions. Br J Haematol 2007;138:587–593.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Di Tucci AA, Matta G, Deplano S et al.. Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias. Haematologica 2008;93:1385–1388.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    St Pierre TG, Clark PR, Chua-Anusorn W et al.. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005;105:855–861.

  • 25

    Olivieri NF, Nathan DG, MacMillan JH et al.. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994;331:574–578.

  • 26

    Wood JC. Cardiac iron across different transfusion-dependent diseases. Blood Rev 2008;22(Suppl 2):14–21.

  • 27

    Modell B, Khan M, Darlison M et al.. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008;10:42.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Wang R, Gross CP, Halene S, Ma X. Comorbidities and survival in a large cohort of patients with newly diagnosed myelodysplastic syndromes. Leuk Res 2009;33:1594–1598.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Buja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med 1971;51:209–221.

  • 30

    Delea TE, Hagiwara M, Phatak PD. Retrospective study of the association between transfusion frequency and potential complications of iron overload in patients with myelodysplastic syndrome and other acquired hematopoietic disorders. Curr Med Res Opin 2009;25:139–147.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Takatoku M, Uchiyama T, Okamoto S et al.. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol 2007;78:487–494.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Kao JM, McMillan A, Greenberg PL. International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: impact of cytopenias on clinical outcomes in myelodysplastic syndromes. Am J Hematol 2008;83:765–770.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Konen E, Ghoti H, Goitein O et al.. No evidence for myocardial iron overload in multitransfused patients with myelodysplastic syndrome using cardiac magnetic resonance T2 technique. Am J Hematol 2007;82:1013–1016.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Park J, Ohyashiki K, Akata S et al.. Evaluation of cardiac iron overload in transfusion-dependent adult marrow failure patients by magnetic resonance imaging. Leuk Res 2009;33:756–758.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Armand P, Kim HT, Cutler CS et al.. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007;109:4586–4588.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    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 (MDS). Biol Blood Marrow Transplant 2008;14:1217–1225.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Malcovati L, Porta MG, 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Schafer AI, Cheron RG, Dluhy R et al.. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981;304:319–324.

  • 39

    Jaeger M, Aul C, Sohngen D et al.. Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes [in German]. Beitr Infusionsther 1992;30:464–468.

  • 40

    Goldberg SL, Mody-Patel N, Chen ER. Clinical and economic consequences of myelodysplastic myndromes in the United States: an analysis of the medicare database [abstract]. Blood 2008;112:Abstract 636.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Chee CE, Steensma DP, Wu W et al.. Neither serum ferritin nor the number of red blood cell transfusions affect overall survival in refractory anemia with ringed sideroblasts. Am J Hematol 2008;83:611–613.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    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 [abstract]. Blood 2008;112:Abstract 640.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Leitch HA. Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy. Leuk Res 2007;31(Suppl 3):S7–9.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Jensen PD, Heickendorff L, Pedersen B et al.. The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996;94:288–299.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Porter JB. Practical management of iron overload. Br J Haematol 2001;115:239–252.

  • 46

    Mahesh S, Ginzburg Y, Verma A. Iron overload in myelodysplastic syndromes. Leuk Lymphoma 2008;49:427–438.

  • 47

    Shashaty G, Frankewich R, Chakraborti T et al.. Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis. Oncology (Williston Park) 2006;20:1799–1806, 1811.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Goldberg SL. Novel treatment options for transfusional iron overload in patients with myelodysplastic syndromes. Leuk Res 2007;31(Suppl 3):S16–22.

  • 49

    Cappellini MD, Bejaoui M, Agaoglu L et al.. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia. Clin Ther 2007;29:909–917.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50

    Wimazal F, Nosslinger T, Baumgartner C et al.. Deferasirox induces regression of iron overload in patients with myelodysplastic syndromes. Eur J Clin Invest 2009;39:406–411.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51

    Cappellini MD, El-Beshlawy A, Kattamis A et al.. Efficacy and safety of deferasirox (Exjade(R)) in patients with transfusion-dependent anemias: 1-year results from the large, prospective, multicenter EPIC study [abstract]. Blood 2008;112:Abstract 3875.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Porter JB, Cappellini MD, El-Beshlawy A et al.. Effect of deferasirox (Exjade(R)) on labile plasma iron levels in heavily iron-overloaded patients with transfusion-dependent anemias enrolled in the large-scale, prospective 1-Year EPIC trial [abstract]. Blood 2008;112:Abstract 3881.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53

    Gattermann N, Schmid M, Porta MD et al.. Efficacy and safety of deferasirox (Exjade(R)) during 1 year of treatment in transfusion-dependent patients with myelodysplastic syndromes: results from EPIC trial [abstract]. Blood 2008;112:Abstract 633.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54

    List AF, Baer MR, Steensma D et al.. Iron chelation with deferasirox (Exjade(R)) improves iron burden in patients with myelodysplastic syndromes (MDS) [abstract]. Blood 2008;112:Abstract 634.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55

    Rachmilewitz E, Merkel D, Ghoti H et al.. Improvement of oxidative stress parameters in MDS patients with iron overload treated with deferasirox [abstract]. Blood 2008;112:Abstract 2675.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    De Witte T, Zwaan F, Hermans J et al.. Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG). Br J Haematol 1990;74:151–155.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57

    Deeg HJ, Shulman HM, Anderson JE et al.. Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood 2000;95:1188–1194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Lucarelli G, Galimberti M, Polchi P et al.. Bone marrow transplantation in patients with thalassemia. N Engl J Med 1990;322:417–421.

  • 59

    Kataoka K, Nannya Y, Hangaishi A et al.. Influence of pretransplantation serum ferritin on nonrelapse mortality and nonmyeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009;15:195–204.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60

    Alessandrino EP, Della Porta MG, 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 study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica 2009; in press.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61

    Altes A, Remacha AF, Sarda P et al.. Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis. Bone Marrow Transplant 2004;34:505–509.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62

    Strasser SI, Kowdley KV, Sale GE, McDonald GB. Iron overload in bone marrow transplant recipients. Bone Marrow Transplant 1998;22:167–173.

  • 63

    Kamble RT, Selby GB, Mims M et al.. Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006;12:506–510.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64

    Greenberg PL, Cosler LE, Ferro SA, Lyman GH. The costs of drugs used to treat myelodysplastic syndromes following National Comprehensive Cancer Network Guidelines. J Natl Compr Canc Netw 2008;6:942–953.

    • PubMed
    • Search Google Scholar
    • Export Citation
Copyright:
Copyright © 2009 by the National Comprehensive Cancer Network 2009
Article Category:
Research Article
Print Publication Date:
01 Dec 2009
Online Publication Date:
Dec 2009
Keywords:
Transfusion; iron chelation; iron overload; myelodysplastic syndromes; thalassemia; MRI; non–transferrin-bound iron
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1008 247 88
PDF Downloads 504 122 8
EPUB Downloads 0 0 0