Advances in Clinical and Experimental Medicine
2016, vol. 25, nr 4, July-August, p. 633–641
Publication type: original article
Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry
1 Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Poland
2 Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland
3 Department of Hematology and Bone Marrow Transplantation, Medical University of Gdańsk, Poland
4 Department of Hematology, Holycross Cancer Center, Kielce, Poland
5 Department of Hematology, Medical University of Lodz, Poland
6 Department of Hematology, Institute of Hematology and Transfusiology, Warszawa, Poland
7 Department of Hematology and Internal Diseases, Military Institute of Medicine, Warszawa, Poland
Background. Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland.
Objectives. The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia.
Material and Methods. We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG).
Results. Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968).
Conclusion. Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish MDS Registry provide important insights. Hyperferritinemia higher than 1000 ng/L can be an important indicator of poor prognosis in MDS.
myelodysplastic syndrome, hyperferritinemia, serum ferritin concentration, red blood cell transfusion dependence, transformation to acute myeloid leukemia
- Cazzola M, Malcovati L: Myelodysplastic syndromes-coping with ineffective hematopoiesis. N Engl J Med 2005, 352, 536–538.
- Malcovati L: Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res 2007, 31, Suppl 3, 2–6.
- Dwilewicz-Trojaczek J, Deptała A, Hellmann A, Mądry K, Podolak-Dawidziak M, Warzocha K: Diagnostics, classification and treatment of myelodysplastic syndromes: guidelines of the Polish Experts Group. Acta Haematol Pol 2010, 41, 101–114.
- Garcia-Manero G: Prognosis of myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program 2010, BRAK, 330–337.
- Balducci L: Transfusion independence in patients with myelodysplastic syndromes: Impact on outcomes and quality of life. Cancer 2006, 106, 2087–2094.
- Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982, 51, 189–199.
- Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J: The World Health Organization classification of hematological malignancies report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Mod Pathol 2000, 13, 193–207.
- Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997, 89, 2079–2088.
- Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D: Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012, 120, 2454–2465.
- Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, Giagounidis A, Hildebrandt B, Bernasconi P, Knipp S, Strupp C, Lazzarino M, Aul C, Cazzola M: Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007, 25, 3503–3510.
- Porter JB: Practical management of iron overload. Br J Hematol 2001, 115, 239–252.
- Hershko C, Peto TE: Non-transferrin plasma iron. Br J Haematol 1987, 66, 149–151.
- Cabantchik ZI, Breuer W, Zanninelli G, Cianciulli P: LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 2005, 18, 277–287.
- Jensen PD: Evaluation of iron overload. Br J Haematol 2004, 124, 697–711.
- Voskaridou E, Douskou M, Terpos E, Papassotiriou I, Stamoulakatou A, Ourailidis A, Loutradi A, Loukopoulos D: Magnetic resonance imaging in the evaluation of iron overload in patients with beta thalassaemia and sickle cell disease. Br J Haematol 2004, 126, 736–742.
- Park S, Sapena R, Kelaidi C, Vassilieff D, Bordessoule D, Stamatoullas A, Cheze S, Beyne-Rauzy O, Vey N, Rose C, Guerci A, Natarajan-Amé S, Tertian G, Slama B, Fenaux P, Dreyfus F: Ferritin level at diagnosis is not correlated with poorer survival in non RBC transfusion dependent lower risk de novo MDS. Leuk Res 2011, 35, 1530–1533.
- Kikuchi S, Kobune M, Iyama S, Sato T, Murase K, Kawano Y, Takada K, Ono K, Hayashi T, Miyanishi K, Sato Y, Takimoto R, Kato J: Prognostic significance of serum ferritin concentration at diagnosis in myelodysplastic syndrome. Int J Hematol 2012, 95, 527–534.
- Mądry K, Machowicz R, Waszczuk-Gajda A, Drozd-Sokołowska J, Hołowiecka BS, Wiater E, Mital A, Obara A, Szmigielska-Kapłon A, Kołkowska-Leśniak A, Sikorska A, Subocz E, Mendrek W, Szczepańska M, Biedroń M, Jachalska A, Wasilewska E, Wojciechowska M, Guzicka-Kazimierczak R, Kopacz A, Katinas K, Kruger W, Dawidowska A, Salamańczuk Z, Zawirska D, Świderska A, Jędrzejczak WW, Dwilewicz-Trojaczek J: Demographic, hematologic, and clinical features of myelodysplastic syndrome patients: Results from the first polish myelodysplastic syndrome registry. Acta Haematol 2015, 134, 125–134.
- Gattermann N, Rachmilewitz EA: Iron overload in MDS-pathophysiology, diagnosis, and complications. Ann Hematol 2011, 90, 1–10.
- Cortelezzi A, Cattaneo C, Cristiani S, Duca L, Sarina B, Deliliers GL, Fiorelli G, Cappellini MD: Non-transferrinbound iron in myelodysplastic syndromes: A marker of ineffective erythropoiesis? Hematol J 2000, 1, 153–158.
- 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. 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 Hematol 2007, 78, 487–494.
- Cakar MK, Yegin ZA, Baysal NA, Altındal S, Pamukçuoğlu M, Celik B, Yenicesu I: Adverse impact of hyperferritinemia and transfusion dependency on treatment success in myelodysplastic syndrome. Transfus Apher Sci 2013, 48, 397–401.
- Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, Wierda WG, Pierce S, Estey E, Liu J, Huang X, Kantarjian H: A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 2008, 22, 538–543.
- Chee CE, Steensa DP, WU W, Hanson CA, Tefferu A: Neither ferritin nor the number of red blood cell transfusions affect overall survival in refractoty anemia with ringed sideroblats. Am J Hematol 2008, 83, 611–613.
- Malcovati L, Porta MG, Cazzola M: Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Hematologica 2006, 91, 1588–1590.
- Goldberg SL, Chen E, Corral M: Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol 2010, 28, 2847–2852.
- Sanz G, Nomdedeu B, Such E, Bernal T, Belkaid M, Ardanaz MT: Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Blood 2008, 112, 238–239.
- Dinmohamed AG, Visser O, van Norden Y, Huijgens PC, Sonneveld P, Loosdrecht A, Jongen-Lavrencic M: Trends in incidence, initial treatment and survival of myelodysplastic syndromes: A population-based study of 5144 patients diagnosed in the Netherlands from 2001 to 2010. Eur J Cancer 2014, 50, 1004–1012.
- McQuilten ZK, Wood EM, Polizotto N, Campbell LJ, Wall M, Curtis DJ, Farrugia H, McNeil JJ, Sundararajan V: Underestimation of myelodysplastic syndrome incidence by cancer registries: Results from a population-based data linkage study. Cancer 2014, 120, 1686.
- Malcovati L: Red blood cell transfusion therapy and iron chelation in patients with myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk 2009, 9, Suppl 3, 305–311.