Abstract
AIMS: To determine whether nontransferrin bound iron is present in the serum of long term survivors of acute leukaemia and bone marrow transplantation who have liver dysfunction as indicated by consistently raised serum aspartate aminotransferase (AST) activities. METHODS: Thirty eight patients, who were at least three years from the end of treatment, were studied. Serum samples were analysed for hepatitis C, hepatitis B, AST, ferritin, and non-transferrin bound iron. A bleomycin based assay was used to detect non-transferrin bound iron. Patient and blood bank records were examined to determine the number of units of transfused blood received by each patient. RESULTS: Ten patients had consistently raised serum AST activities. Of these, two had evidence of hepatitis C infection, one had chronic hepatitis B infection and one had chronic graft versus host disease affecting the liver. None of these four patients had detectable non-transferrin bound iron. The remaining six patients had no obvious reason for raised AST activities, but four had non-transferrin bound iron detectable in their serum as compared with only two out of 28 patients with normal AST activities. Patients with abnormal AST activities had higher serum ferritin concentrations than those with normal AST, though serum ferritin was raised in 21 of 28 patients without liver dysfunction. CONCLUSION: Non-transferrin bound iron may be found in this group of patients, suggesting that iron overload is the cause of the observed liver dysfunction. Non-transferrin bound iron may also be a more specific indicator of iron overload than the serum ferritin concentrations.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aricò M., Maggiore G., Silini E., Bono F., Viganò C., Cerino A., Mondelli M. U. Hepatitis C virus infection in children treated for acute lymphoblastic leukemia. Blood. 1994 Nov 1;84(9):2919–2922. [PubMed] [Google Scholar]
- Armitage J. O., Burns C. P., Kent T. H. Liver disease complicating the management of acute leukemia during remission. Cancer. 1978 Feb;41(2):737–742. doi: 10.1002/1097-0142(197802)41:2<737::aid-cncr2820410246>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
- Batey R. G., Lai Chung Fong P., Shamir S., Sherlock S. A non-transferrin-bound serum iron in idiopathic hemochromatosis. Dig Dis Sci. 1980 May;25(5):340–346. doi: 10.1007/BF01308057. [DOI] [PubMed] [Google Scholar]
- Blum R. H., Carter S. K., Agre K. A clinical review of bleomycin--a new antineoplastic agent. Cancer. 1973 Apr;31(4):903–914. doi: 10.1002/1097-0142(197304)31:4<903::aid-cncr2820310422>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- Ferri C., Caracciolo F., Zignego A. L., La Civita L., Monti M., Longombardo G., Lombardini F., Greco F., Capochiani E., Mazzoni A. Hepatitis C virus infection in patients with non-Hodgkin's lymphoma. Br J Haematol. 1994 Oct;88(2):392–394. doi: 10.1111/j.1365-2141.1994.tb05036.x. [DOI] [PubMed] [Google Scholar]
- Garson J. A., Tuke P. W., Makris M., Briggs M., Machin S. J., Preston F. E., Tedder R. S. Demonstration of viraemia patterns in haemophiliacs treated with hepatitis-C-virus-contaminated factor VIII concentrates. Lancet. 1990 Oct 27;336(8722):1022–1025. doi: 10.1016/0140-6736(90)92487-3. [DOI] [PubMed] [Google Scholar]
- Gutteridge J. M., Hou Y. Y. Iron complexes and their reactivity in the bleomycin assay for radical-promoting loosely-bound iron. Free Radic Res Commun. 1986;2(3):143–151. doi: 10.3109/10715768609088066. [DOI] [PubMed] [Google Scholar]
- Gutteridge J. M., Rowley D. A., Griffiths E., Halliwell B. Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin Sci (Lond) 1985 Apr;68(4):463–467. doi: 10.1042/cs0680463. [DOI] [PubMed] [Google Scholar]
- Gutteridge J. M., Rowley D. A., Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts. Detection of 'free' iron in biological systems by using bleomycin-dependent degradation of DNA. Biochem J. 1981 Oct 1;199(1):263–265. doi: 10.1042/bj1990263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halliwell B., Aruoma O. I., Mufti G., Bomford A. Bleomycin-detectable iron in serum from leukaemic patients before and after chemotherapy. Therapeutic implications for treatment with oxidant-generating drugs. FEBS Lett. 1988 Dec 5;241(1-2):202–204. doi: 10.1016/0014-5793(88)81061-5. [DOI] [PubMed] [Google Scholar]
- Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates: is it a mechanism for hydroxyl radical production in biochemical systems? FEBS Lett. 1978 Aug 15;92(2):321–326. doi: 10.1016/0014-5793(78)80779-0. [DOI] [PubMed] [Google Scholar]
- Harrison P., Marwah S. S., Hughes R. T., Bareford D. Non-transferrin bound iron and neutropenia after cytotoxic chemotherapy. J Clin Pathol. 1994 Apr;47(4):350–352. doi: 10.1136/jcp.47.4.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hetherington M. L., Buchanan G. R. Elevated serum transaminase values during therapy for acute lymphoblastic leukemia correlate with prior blood transfusions. Cancer. 1988 Oct 15;62(8):1614–1618. doi: 10.1002/1097-0142(19881015)62:8<1614::aid-cncr2820620826>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
- Kirk J. A., Raghupathy P., Stevens M. M., Cowell C. T., Menser M. A., Bergin M., Tink A., Vines R. H., Silink M. Growth failure and growth-hormone deficiency after treatment for acute lymphoblastic leukaemia. Lancet. 1987 Jan 24;1(8526):190–193. doi: 10.1016/s0140-6736(87)90004-3. [DOI] [PubMed] [Google Scholar]
- Kolho E., Oksanen K., Honkanen E., Naukkarinen R., Krusius T. Hepatitis C antibodies in dialysis patients and patients with leukaemia. J Med Virol. 1993 Aug;40(4):318–321. doi: 10.1002/jmv.1890400410. [DOI] [PubMed] [Google Scholar]
- Livesey S. J., Holmes J. A., Whittaker J. A. Ocular complications of bone marrow transplantation. Eye (Lond) 1989;3(Pt 3):271–276. doi: 10.1038/eye.1989.37. [DOI] [PubMed] [Google Scholar]
- Locasciulli A., Gornati G., Tagger A., Ribero M. L., Cavalletto D., Cavalletto L., Masera G., Shulman H. M., Portmann B., Alberti A. Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Blood. 1991 Sep 15;78(6):1619–1622. [PubMed] [Google Scholar]
- McKay P. J., Murphy J. A., Cameron S., Burnett A. K., Campbell M., Tansey P., Franklin I. M. Iron overload and liver dysfunction after allogeneic or autologous bone marrow transplantation. Bone Marrow Transplant. 1996 Jan;17(1):63–66. [PubMed] [Google Scholar]
- Perry M. C. Chemotherapeutic agents and hepatotoxicity. Semin Oncol. 1992 Oct;19(5):551–565. [PubMed] [Google Scholar]
- Prieto J., Barry M., Sherlock S. Serum ferritin in patients with iron overload and with acute and chronic liver diseases. Gastroenterology. 1975 Mar;68(3):525–533. [PubMed] [Google Scholar]
- Von Hoff D. D., Rozencweig M., Layard M., Slavik M., Muggia F. M. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med. 1977 Feb;62(2):200–208. doi: 10.1016/0002-9343(77)90315-1. [DOI] [PubMed] [Google Scholar]
- Worwood M., Cragg S. J., Jacobs A., McLaren C., Ricketts C., Economidou J. Binding of serum ferritin to concanavalin A: patients with homozygous beta thalassaemia and transfusional iron overload. Br J Haematol. 1980 Nov;46(3):409–416. doi: 10.1111/j.1365-2141.1980.tb05987.x. [DOI] [PubMed] [Google Scholar]
- Worwood M., Dawkins S., Wagstaff M., Jacobs A. The purification and properties of ferritin from human serum. Biochem J. 1976 Jul 1;157(1):97–103. doi: 10.1042/bj1570097. [DOI] [PMC free article] [PubMed] [Google Scholar]
