Ethical issues and risk/benefit assessment of iron chelation therapy: Advances with deferiprone/deferoxamine combinations and concerns about the safety, efficacy and costs of deferasirox
Abstract
New developments in the area of iron and other metal metabolism and toxicity and the effects and uses of chelators have been presented at the 16th International Conference on Chelation (ICOC), Limassol, Cyprus in October 2006. Marketing practices by pharmaceutical companies, contradictory policies by regulatory authorities and ineffective policies by health authorities deprive thousands of thalassemia and other transfused patients of life saving iron chelating drugs and of efficacious chelation treatments. Thousands of patients were using deferasirox (DFRA) worldwide a few months after the European Union (EU) authorities, and about 1 year after the Food and Drugs Administration (FDA), proceeded to its accelerated approval with no sufficient evidence that the drug was efficacious, especially for clearing excess cardiac iron, and also safe. Cases of fatal, acute, irreversible renal and liver failure, fatal agranulocytosis and other toxicities have recently been reported with DFRA. The FDA has not yet approved deferiprone (L1) depriving thousands of patients of potentially life saving treatment. The high cost of DFRA at 60 euros/g, L1 at 5.5 euros/g and deferoxamine (DFO) at 8.3 euros/g, diminishes the prospects of universal chelation therapy, especially for patients in developing countries. The safety and efficacy record of L1, DFO, and their combination in particular, appear to provide universal solutions in the treatment of transfusional iron overload, and also in reducing mortality because of their ability to clear rapidly and effectively excess cardiac iron.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Due to serious side effects, the applicability of iron chelators during cancer treatment is hampered.
“Unfortunately, due to serious side effects in several cases, e.g., hearing abnormalities, nephropathy, optic neuropathy, and growth failure in children, their applicability during cancer treatment is hampered [135,139].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [139]
Cites
Intramuscular desferrioxamine in patients with Alzheimer's disease
MCLACHLAN, D. (1991) · The Lancet · doi:10.1016/0140-6736(91)92978-b · Cited by 764 · see citing works
Survival in β-thalassaemia major in the UK: data from the UK Thalassaemia Register
Modell, B., Khan, M., & Darlison, M. W. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02357-6 · Cited by 587 · see citing works
Pennell, D. J. (2005) · Blood · doi:10.1182/blood-2005-07-2948 · Cited by 490 · see citing works
Anderson, L. J., Wonke, B., Prescott, E., Holden, S., Walker, J. M., & Pennell, D. J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09740-4 · Cited by 431 · see citing works
Nisbet‐Brown, E., Olivieri, N. F., Giardina, P. J., Grady, R. W., Neufeld, E. J., Séchaud, R., Krebs‐Brown, A., Anderson, J. R., Alberti, D., Sizer, K. C., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13309-0 · Cited by 326 · see citing works
Vichinsky, E. P., Onyekwere, O. C., Porter, J. B., Swerdlow, P. S., Eckman, J. R., Lane, P., Files, B. A., Hassell, K. L., Kelly, P. F., Wilson, F. L., et al. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06455.x · Cited by 267 · see citing works
Telfer, P. T., Coen, P. G., Christou, S., Hadjigavriel, M., Kolnakou, A., Pangalou, E., Pavlides, N., Psiloines, M., Simamonian, K., Skordos, G., et al. (2006) · PubMed · Cited by 190 · see citing works
Galanello, R., Piga, A. G., Alberti, D., Rouan, M. C., Bigler, H., & Séchaud, R. (2003) · PubMed · Cited by 169 · see citing works
Development of Tridentate Iron Chelators: From Desferrithiocin to ICL670
Nick, H., Acklin, P., Lattmann, R., Buehlmayer, P., Hauffe, S., Schupp, J., & Alberti, D. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033457610 · Cited by 167 · see citing works
Galanello, R., Piga, A. G., Alberti, D., Rouan, M. C., Bigler, H., & Séchaud, R. (2003) · The Journal of Clinical Pharmacology · doi:10.1177/0091270003253350 · Cited by 140 · see citing works
Kontoghiorghes, G. J., Eracleous, E., Economides, C. P., & Kolnagou, A. (2005) · Current Medicinal Chemistry · doi:10.2174/092986705774463003 · Cited by 125 · see citing works
Benefits and Risks of Deferiprone in Iron Overload in Thalassaemia and Other Conditions
Kontoghiorghes, G. J., Neocleous, K., & Kolnagou, A. (2003) · Drug Safety · doi:10.2165/00002018-200326080-00003 · Cited by 112 · see citing works
Kontoghiorghes, G. J., Pattichis, K., Neocleous, K., & Kolnagou, A. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043364685 · Cited by 112 · see citing works
Simple synthesis of the potent iron chelators 1-alkyl-3-hydroxy-2-methylpyrid-4-ones
Kontoghiorghes, G. J., & Sheppard, L. N. (1987) · Inorganica Chimica Acta · doi:10.1016/s0020-1693(00)85549-8 · Cited by 104 · see citing works
Deferasirox and deferiprone remove cardiac iron in the iron-overloaded gerbil
Wood, J. C., Otto‐Duessel, M., Gonzalez, I., Aguilar, M. I., Shimada, H., Nick, H., Nelson, M. D., & Moats, R. A. (2006) · Translational research · doi:10.1016/j.trsl.2006.05.005 · Cited by 81 · see citing works
Delea, T. E., Sofrygin, O., Thomas, S. K., Baladi, J., Phatak, P. D., & Coates, T. D. (2007) · PharmacoEconomics · doi:10.2165/00019053-200725040-00005 · Cited by 79 · see citing works
Kontoghiorghes, G. J. (2007) · Expert Opinion on Drug Safety · doi:10.1517/14740338.6.3.235 · Cited by 68 · see citing works
Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia
Henter, J., & Karlén, J. (2007) · Blood · doi:10.1182/blood-2007-02-065805 · Cited by 65 · see citing works
Peng, C., Chow, K., Chen, J., Chiang, Y., Lin, T., & Tsai, C. (2003) · European Journal Of Haematology · doi:10.1034/j.1600-0609.2003.00071.x · Cited by 58 · see citing works
YAMAMOTO, R. S., Williams, G. M., Frankel, H. H., & Weisburger, J. H. (1971) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(71)90300-0 · Cited by 55 · see citing works
Kolnagou, A., & Kontoghiorghes, G. J. (2006) · Hemoglobin · doi:10.1080/03630260600642567 · Cited by 46 · see citing works
Reversal of heart failure in thalassemia major by combined chelation therapy: a case report
Tsironi, M., Deftereos, S., Andriopoulos, P., Farmakis, D. T., Meletis, J., & Aessopos, A. (2004) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2004.00335.x · Cited by 45 · see citing works
Chelators affecting iron absorption in mice.
Kontoghiorghes, G. J. (1990) · PubMed · Cited by 41 · see citing works
Kolnagou, A., Fessas, C., Papatryphonas, A., Economides, C. P., & Kontoghiorghes, G. J. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.05195.x · Cited by 33 · see citing works
Kontoghiorghes, G. J. (2006) · Hemoglobin · doi:10.1080/03630260600642674 · Cited by 33 · see citing works
Deferasirox: An effective once-daily orally active iron chelator
Porter, J. B. (2006) · Drugs of today · doi:10.1358/dot.2006.42.10.1009901 · Cited by 29 · see citing works
Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis.
Shashaty, G. G., Frankewich, R., Chakraborti, T., Choudary, J. B., Al‐Fayoumi, S., Kacuba, A., Castillo, S., Robie‐Suh, K., Rieves, D., Weiss, K., et al. (2006) · PubMed · Cited by 24 · see citing works
Do we need more iron-chelating drugs?
Kontoghiorghes, G. J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14085-8 · Cited by 23 · see citing works
New iron-chelating drugs for the treatment of transfusional iron overload and other diseases
Kotonghiorghes, G. J. (2005) · Drugs of the Future · doi:10.1358/dof.2005.030.12.942323 · Cited by 10 · see citing works
Brissot, P., Deugnier, Y., Cianciulli, P., Cario, H., Jeng, M., & Rabault, B. (2006) · Blood · doi:10.1182/blood.v108.11.3817.3817 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Wang, Y., Lei, Y., Ding, J. P., & Chen, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010095 · Cited by 297 · see citing works
Iron as a central player and promising target in cancer progression
Jung, M., Mertens, C., Tomat, E., & Brüne, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020273 · Cited by 268 · see citing works
“, hearing abnormalities, nephropathy, optic neuropathy, and growth failure in children, their applicability during cancer treatment is hampered [135,139].”
BackgroundKontoghiorghes, G. J., & Kontoghiorghe, C. (2016) · Drug Design Development and Therapy · doi:10.2147/dddt.s79458 · Cited by 176 · see citing works
Ferroptosis: mechanisms and therapeutic targets
Zhou, Q., Meng, Y., Le, J., Sun, Y., Dian, Y., Yao, L., Xiong, Y., Zeng, F., Chen, X., & Deng, G. (2024) · MedComm · doi:10.1002/mco2.70010 · Cited by 83 · see citing works
Fanconi Syndrome Due to Deferasirox
Rafat, C., Fakhouri, F., Ribeil, J., Delarue, R., & Quintrec, M. L. (2009) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2009.03.013 · Cited by 74 · see citing works
Acquired Proximal Renal Tubular Dysfunction in β-Thalassemia Patients Treated With Deferasirox
Yacobovich, J., Stark, P., Barzilai‐Birenbaum, S., Krause, I., Pazgal, I., Yaniv, I., & Tamary, H. (2010) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0b013e3181ec0c38 · Cited by 58 · see citing works
World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients
Kontoghiorghe, C. (2014) · World Journal of Methodology · doi:10.5662/wjm.v4.i3.163 · Cited by 59 · see citing works
New developments and controversies in iron metabolism and iron chelation therapy
Kontoghiorghe, C., & Kontoghiorghes, G. J. (2016) · World Journal of Methodology · doi:10.5662/wjm.v6.i1.1 · Cited by 52 · see citing works
Kolnagou, A., Kleanthous, M., & Kontoghiorghes, G. J. (2010) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2010.01499.x · Cited by 51 · see citing works
Heidari, R. (2019) · Toxicology · doi:10.1016/j.tox.2019.05.002 · Cited by 50 · see citing works
Kontoghiorghes, G. J. (2009) · Hemoglobin · doi:10.3109/03630260903217182 · Cited by 40 · see citing works
Zhou, Y., Que, K., Tang, H., Zhang, P., Fu, Q., & Liu, Z. (2020) · Oncology Letters · doi:10.3892/ol.2020.12161 · Cited by 38 · see citing works
Fanconi syndrome in a patient with β‐thalassemia major after using deferasirox for 27 months
Wei, H., Yang, C., Cheng, C., & Lo, F. (2010) · Transfusion · doi:10.1111/j.1537-2995.2010.02939.x · Cited by 34 · see citing works
Ocular abnormalities in multi-transfused beta-thalassemia patients
Heydarian, S., Jafari, R., Karami, H., Shektaei, M., Dailami, K. N., Amiri, A. A., Rezaee, M. R. S., & Far, A. F. (2015) · Indian Journal of Ophthalmology · doi:10.4103/0301-4738.170986 · Cited by 34 · see citing works
Myelodysplasia paranoia: Iron as the new radon
Steensma, D. P. (2008) · Leukemia Research · doi:10.1016/j.leukres.2008.10.017 · Cited by 34 · see citing works
Kolnagou, A., & Kontoghiorghes, G. J. (2009) · Hemoglobin · doi:10.3109/03630260903212043 · Cited by 31 · see citing works
Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases
Kolnagou, A. (2014) · World Journal of Methodology · doi:10.5662/wjm.v4.i4.197 · Cited by 29 · see citing works
Kontoghiorghes, G. J. (2010) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2010.497138 · Cited by 29 · see citing works
Effectiveness of deferiprone in transfusion‐independent beta‐thalassemia/HbE patients
Akrawinthawong, K., Chaowalit, N., Chatuparisuth, T., & Siritanaratkul, N. (2011) · Hematology · doi:10.1179/102453311x12940641877768 · Cited by 26 · see citing works
Iron-chelation therapy with oral chelators in patients with thalassemia major
Uygun, V., & Kurtoğlu, E. (2013) · Hematology · doi:10.1179/1607845412y.0000000046 · Cited by 22 · see citing works
The emerging role and therapeutical implications of ferroptosis in wound healing
Zhao, Y., Chen, Z., Xie, S., Xiao, F., Hu, Q., & Ju, Z. (2024) · Burns & Trauma · doi:10.1093/burnst/tkae082 · Cited by 21 · see citing works
Gama, S., Dron, P. I., Chaves, S., Farkas, E., & Santos, M. A. (2009) · Dalton Transactions · doi:10.1039/b904950a · Cited by 21 · see citing works
Rodríguez‐Lucena, D., Gaboriau, F., Rivault, F., Schalk, I. J., Lescoat, G., & Mislin, G. L. A. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.11.057 · Cited by 18 · see citing works
Deferasirox induced liver injury in haemochromatosis.
Aslam, N., Mettu, P., Marsano, L. S., & Martin, A. (2010) · PubMed · Cited by 17 · see citing works
Kontoghiorghes, G. J. (2008) · Hemoglobin · doi:10.1080/03630260802341703 · Cited by 17 · see citing works
Steensma, D. P. (2011) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-011-0084-z · Cited by 16 · see citing works
Porter, J. B., Taher, A. T., Cappellini, M. D., & Vichinsky, E. P. (2008) · Hemoglobin · doi:10.1080/03630260802342008 · Cited by 16 · see citing works
Ioannidis, I., Lefkaritis, G., Georgiades, S. N., Pashalidis, I., & Kontoghiorghes, G. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115954 · Cited by 15 · see citing works
Miller, S. C., Wang, X., & Bowman, B. M. (2010) · Health Physics · doi:10.1097/hp.0b013e3181bfb99b · Cited by 14 · see citing works
TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo
Kalanaky, S., Hafizi, M., Safari, S., Mousavizadeh, K., Kabiri, M., Farsinejad, A., Fakharzadeh, S., & Nazaran, M. H. (2016) · International Journal of Hematology · doi:10.1007/s12185-015-1932-8 · Cited by 12 · see citing works
Al-Kherbash, H. A., Al-Awdi, A., & Hasan, N. S. (2017) · The Scientific Journal of Al-Azhar Medical Faculty Girls · doi:10.4103/sjamf.sjamf_15_17 · Cited by 12 · see citing works
Refractive errors and ocular biometry components in thalassemia major patients
Heydarian, S., Jafari, R., & Karami, H. (2015) · International Ophthalmology · doi:10.1007/s10792-015-0161-8 · Cited by 10 · see citing works
Greenshields, A. L., Coombs, M. R. P., Fernando, W., Holbein, B. E., & Hoskin, D. W. (2019) · BioMetals · doi:10.1007/s10534-019-00222-3 · Cited by 9 · see citing works
Kontoghiorghes, G. J. (2008) · Expert Opinion on Drug Safety · doi:10.1517/14740330802137479 · Cited by 9 · see citing works
Kontoghiorghes, G. J. (2011) · Hemoglobin · doi:10.3109/03630269.2011.576906 · Cited by 9 · see citing works
Puzzling out iron complications in cancer drug resistance
Abedi, M., & Rahgozar, S. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103772 · Cited by 8 · see citing works
Is Deferasirox Implicated in Multiple Organ Failure in a Patient With Homozygous β-Thalassemia?
Vlachaki, E., Chatzinikolaou, K., Bekiari, E., Klonizakis, P., & Τσάπας, Α. (2011) · Angiology · doi:10.1177/0003319710394160 · Cited by 6 · see citing works
Síndrome de hipersensibilidad retardada inducido por deferasirox
Macías, A. G., Palacios, E. L., Olabarría, I., & Odriozola, P. M. (2009) · Medicina Clínica · doi:10.1016/j.medcli.2008.12.004 · Cited by 5 · see citing works
Hawsawi, Z. M. A., Sairafy, M. H., Tarawah, A., Zolaly, M. A., & Hegaily, A. R. S. A. (2010) · Journal of Taibah University Medical Sciences · doi:10.1016/s1658-3612(10)70121-9 · Cited by 4 · see citing works
Kontoghiorghes, G. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031364 · Cited by 4 · see citing works
Physico-Chemical Properties of bis -2-(2-Hydroxyphenyl)-thiazole-carboxamide (BHPTC) Chelators
Hmadeh, M., Mazan, V., Rodríguez‐Lucena, D., Hoegy, F., Platas‐Iglesias, C., Mislin, G. L. A., & Elhabiri, M. (2026) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.5c05413 · Cited by 1 · see citing works
Meyboom, R. H. B. (2007) · Side effects of drugs annual · doi:10.1016/s0378-6080(06)29023-8
Impact of new chelating agents on ocular abnormalities in β-thalassemia major patients
Abo-Zied, S., Elgemaey, H. M., & Abd-Aal, H. (2021) · Alexandria Journal of Pediatrics · doi:10.4103/ajop.ajop_33_21
Sullivan, J. E., & McDonald, M. (2014) · Springer eBooks · doi:10.1007/978-1-4471-6362-6_50
(2015) · Elsevier eBooks · doi:10.1016/b978-0-444-53717-1.00063-9
Meyboom, R. H. B. (2010) · Side effects of drugs annual · doi:10.1016/s0378-6080(10)32023-x
Iron Chelator Drugs in Transfusion Dependent Thalassemia: a Review
Hashemieh, M. (2020) · Armaghane Danesh · doi:10.52547/armaghanj.25.4.529
Epidemiological features and clinical profile of patients with thalassemia in Kabul, Afganisthan
Saeed, K. M. I. (2024) · Journal of Hematology and Allied Sciences · doi:10.25259/jhas_28_2024
Barzegari, S., Rostamian, H., Firoozi-Majd, E., & Arpacı, İ. (2025) · Pharmacy · doi:10.3390/pharmacy13030086
- Authors
- Kontoghiorghes, G. J.
- Corresponding author
- Kontoghiorghes, George J.
- Venue
- Hemoglobin
- Publisher
- Informa UK Limited
- Published
- 2008-01
- Volume
- 32
- Issue
- 1-2
- Pages
- 1-15
- ISSN
- 0363-0269 (ISSN-L)
- 1532-432X
- OpenAlex
- W2013938992
- Cited by
- 49
- References
- 30
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 1
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hemoglobin (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
- Keywords
- iron chelation therapy, deferasirox, deferiprone, deferoxamine, transfusional iron overload, thalassemia, cardiac iron, drug safety, drug efficacy, drug costs, accelerated approval, renal failure, liver failure, agranulocytosis, regulatory policy, pharmaceutical marketing
- MeSH terms
- Deferiprone, Deferasirox, Benzoates, Deferoxamine, Drug Therapy, Combination, Humans, Iron, Iron Chelating Agents, Pyridones, Thalassemia, Triazoles, Chelation Therapy, Siderophores, Drug Approval, Risk Assessment, Iron Overload
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review