Skip to main content

Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia

  • Chapter
  • First Online:
Noncommunicable Diseases

Abstract

Children with severe aplastic anemia (AA) require multiple transfusions of the red blood cells during the immunosuppressive therapy. This leads to iron overload and manifests as elevated levels of ferritin in blood. The aim of this study was a retrospective analysis of the influence of the elevated serum ferritin on the overall survival, event-free survival, the risk of relapse, and response to treatment in children with AA during immunosuppressive therapy. We analyzed 38 children with AA (19 girls, 19 boys, aged 2–17 years) treated according to the obligatory protocol for AA in Poland. The response rate was assessed on days 84, 112, and 360. Patients were divided into three groups: group I consisted of children with ferritin below 285 ng/mL (6 children), group II with ferritin between 286 and 1,000 ng/mL (13 children), and group III ferritin >1,000 ng/mL (19 children). Kaplan-Meier plot was used to estimate the overall survival and event-free survival. We found the overall survival did not differ between the three groups. Event-free survival was significantly shorter (p = 0.03) in patients with ferritin levels >1,000 ng/mL compared with the groups with ferritin bellow 1,000 ng/mL. The time to relapse was significantly shorter in group III than in the other two groups (p = 0.02). We also found the differences in the treatment response at day 84 (p = 0.03) and day 112 (p < 0.0001) of immunosuppressive therapy. These findings confirm a negative influence of iron overload in children with AA on the effect of treatment and the risk of relapse.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Altès A, Remacha AF, Sureda A, Martino R, Briones J, Canals C, Brunet S, Sierra J, Gimferrer E (2002) Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation. Bone Marrow Transplant 29:987–989

    Article  PubMed  Google Scholar 

  • Bagby GC, Lipton JM, Sloand EM, Schiffer CA (2004) Marrow failure. In: Hematology ASH Education Book 1:318–336

    Google Scholar 

  • Camitta BM (2000) What is the definition of cure for aplastic anemia? Acta Haematol 103:16–18

    Article  CAS  PubMed  Google Scholar 

  • Cappellini MD, Porter J, El-Beshlawy A, Li CK, Seymour JF, Elalfy M, Gattermann N, Giraudier S, Lee JW, Chan LL, Lin KH, Rose C, Taher A, Thein SL, Viprakasit V, Habr D, Domokos G, Roubert B, Kattamis A on behalf of the EPIC study investigators A (2010) Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica 95:557–566

    Google Scholar 

  • Chang MH, Kim KH, Kim HS, Jun HJ, Kim DH, Jang JH, Kim K, Jung CW (2010) Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia. Eur J Haematol 82:154–159

    Article  Google Scholar 

  • Deyell RJ, Shereck EB, Milner RA, Schultz KR (2011) Immunosuppressive therapy without hematopoietic growth factor exposure in pediatric acquired aplastic anemia. J Pediatr Hematol Oncol 28(6):469–478

    Article  CAS  Google Scholar 

  • Hoffbrand AV, Taher A, Cappellini MD (2012) How I treat transfusional iron overload. Blood 120:3657–3669

    Article  CAS  PubMed  Google Scholar 

  • Koh KN, Park M, Kim BE, Im HJ, Seo JJ (2010) Restoration of hematopoiesis after iron chelation therapy with deferasirox in 2 children with severe aplastic anemia. J Pediatr Hematol Oncol 32:611–614

    Article  PubMed  Google Scholar 

  • Lee JW (2008) Iron chelation therapy in the myelodysplastic syndromes and aplastic anemia: a review of experience in South Korea. Int J Hematol 88:16–23

    Article  PubMed Central  PubMed  Google Scholar 

  • Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, Habr D, Domokos G, Roubert B, Porter JB (2010) Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial. Blood 116:2448–2454

    Article  CAS  PubMed  Google Scholar 

  • Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, El-Ali A, Habr D, Martin N, Porter JB (2013) Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study. Haematologica 98:1045–1048

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, Passamonti F, Arcaini L, Maffioli M, Bernasconi P, Lazzarino M, Cazzola M (2005) Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 23:7594–7603

    Article  PubMed  Google Scholar 

  • Malcovati L, Porta MG, Cazzola M (2006) Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica 91:1588–1590

    PubMed  Google Scholar 

  • Oliva EN, Ronco F, Marino A, Alati C, Pratico G, Nobile F (2010) Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients. Transfusion 50:1568–1570

    Article  PubMed  Google Scholar 

  • Pawelec K, Matysiak M, Niewiadomska E, Rokicka-Milewska R, Kowalczyk J, Stefaniak J, Balwierz W, Załecka-Czerpko E, Chybicka A, Szmyd K, Sońta-Jakimczyk D, Bubała H, Krauze A, Wysocki M, Kurylak A, Wachowiak J, Grund G, Młynarski W, Bulas M, Krawczuk-Rybak M, Leszczyńska E, Urasiński T, Peregud-Pogorzelski J, Balcerska A, Wlazłowski M (2008) Results of immunosuppressive therapy in children with severe aplastic anaemia. Report of the Polish Paediatric Haematology Group. Med Wieku Rozwoj 12:1092–1097

    PubMed  Google Scholar 

  • Pawelec K, Salamonowicz M, Panasiuk A, Demkow U, Kowalczyk J, Balwierz W, Zaleska-Czepko E, Chybicka A, Szmyd K, Szczepanski T, Bubala H, Wysocki M, Kurylak A, Wachowiak J, Szpecht D, Młynarski W, Bulas M, Krawczuk-Rybak M, Leszczynska E, Urasinski T, Peregud-Pogorzelski J, Balcerska A, Kaczorowska-Hac B, Matysiak M (2015) First-Line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin. Adv Exp Med Biol 836:55–62

    Article  CAS  PubMed  Google Scholar 

  • Porter J, Galanello R, Saglio G, Neufeld EJ, Vichinsky E, Cappellini MD, Olivieri N, Piga A, Cunningham MJ, Soulières D, Gattermann N, Tchernia G, Maertens J, Giardina P, Kwiatkowski J, Quarta G, Jeng M, Forni GL, Stadler M, Cario H, Debusscher L, Della Porta M, Cazzola M, Greenberg P, Alimena G, Rabault B, Gathmann I, Ford JM, Alberti D, Rose C (2008) Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study. Eur J Haematol 80:168–176

    CAS  PubMed Central  PubMed  Google Scholar 

  • Romiszewski M, Gołębiowska-Staroszczyk S, Adamowicz-Salach A, Siwicka A, Matysiak M (2011) The use of chelation therapy in the treatment of iron overload in a girl with Diamond-Blackfan anemia – a case report. Nowa Pediatr 4:90–94

    Google Scholar 

  • Storey JA, Connor RF, Lewis ZT, Hurd D, Pomper G, Keung YK, Grover M, Lovato J, Torti SV, Torti FM, Molnár I (2009) The transplant iron score as a predictor of stem cell transplant survival. J Hematol Oncol 2(44):1–9

    Google Scholar 

  • Takatoku M, Uchiyama T, Okamoto S, Kanakura Y, Sawada K, Tomonaga M, Nakao S, Nakahata T, Harada M, Murate T, Ozawa K, Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes (2007) Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative influence of iron overload on morbidity/mortality. Eur J Haematol 78:487–494

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katarzyna Pawelec .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Pawelec, K. et al. (2015). Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia. In: Pokorski, M. (eds) Noncommunicable Diseases. Advances in Experimental Medicine and Biology(), vol 866. Springer, Cham. https://doi.org/10.1007/5584_2015_148

Download citation

Publish with us

Policies and ethics