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Pulmonary Syndrome in Patients With Thalassemia Major Receiving Intravenous Deferoxamine Infusions

Pulmonary Syndrome in Patients With Thalassemia Major Receiving Intravenous Deferoxamine Infusions Abstract • Eight patients with transfusion-dependent thalassemia major were given continuous intravenous infusions of the chelator, deferoxamine mesylate, to reduce iron overload. Within 5 to 9 days of starting the infusions, four patients developed a pulmonary syndrome of moderate to life-threatening severity characterized by tachypnea, hypoxemia, and a diffuse interstitial pattern on chest roentgenogram. Pulmonary function studies showed restrictive dysfunction. Lung biopsy showed diffuse abnormalities with alveolar damage, interstitial fibrosis, and inflammation. The inflammatory infiltrate comprised lymphocytes, eosinophils, and mast cells. Exposure of the biopsy specimen to fluorescein-conjugated anti-IgE antibody showed fixation of IgE to the mast cell surface, suggesting a hypersensitivity reaction. Detailed studies failed to identify an infectious agent. The temporal relationship between drug administration and lung disease, and the clinical similarities in the four affected patients, strongly suggested a cause and effect relationship. We recommend that therapy with continuous intravenous infusions of deferoxamine be monitored carefully with respect to pulmonary status. (AJDC. 1990;144:565-569) References 1. Sephton-Smith R. Iron excretion in thalassemia major after administration of chelating agents . Br Med J . 1962;2:1577-1580.Crossref 2. Wolfe L, Sallan D, Nathan DG. Current therapy and new approaches to the treatment of thalassemia major . Ann NY Acad Sci . 1985;445:248-255.Crossref 3. Graziano JH, Markenson A, Miller DR, et al. Chelation therapy in beta-thalassemia major, I: intravenous and subcutaneous deferoxamine . J Pediatr . 1978;92:648-652.Crossref 4. Cohen A, Mizanin J, Schwartz E. High-dose intravenous chelation therapy with deferoxamine . In: Buckner CD, Gale RP, Lucarelli G, eds. Advances and Controversies in Thalassemia Therapy . New York, NY: Alan R. Liss Inc; 1989:125-131. 5. Modell B, Berdoukas V. The Clinical Approach to Thalassemia . New York, NY: Grune & Stratton; 1984. 6. Engle MA, Erlandson M, Smith CH. Late cardiac complications of chronic, severe, refractory anemia with hemochromatosis . Circulation . 1967; 30:698-705.Crossref 7. Lederman HM, Cohen A, Lee JWW, Freedman MH, Gelfand EW. Deferoxamine: a reversible S-phase inhibitor of human lymphocyte proliferation . Blood . 1984;64:748-753. 8. Blatt J, Stitely S. Antineuroblastoma activity of deferoxamine in human cell lines . Cancer Res . 1987;47:1749-1750. 9. Estrov Z, Cohen A, Gelfand EW, Freedman MH. Cytotoxicity in vitro of deferoxamine on human marrow hematopoietic progenitors . Toxicology In Vitro . 1988;2:131-134.Crossref 10. Estrov Z, Tawa A, Wang X, et al. In vitro and in vivo effects of deferoxamine in neonatal acute leukemia . Blood . 1987;69:757-761. 11. Kaplinsky C, Estrov Z, Freedman MH, Gelfand EW, Cohen A. Effect of deferoxamine on DNA synthesis, DNA repair, cell proliferation, and differentiation on HL-60 cells . Leukemia . 1987;1:437-441. 12. Miller KB, Rosenwasser LJ, Bessette JM, et al. Rapid desensitization for deferoxamine anaphylactic reaction . Lancet . 1981;1:1059.Crossref 13. Walker JA, Sherman RA, Eisinger RP. Thrombocytopenia associated with intravenous desferrioxamine . Am J Kidney Dis . 1985;6:254-256.Crossref 14. Batey R, Scott J, Jain S, Sherlock S. Acute renal insufficiency occurring during intravenous desferrioxamine therapy . Scand J Haematol . 1979;22:277-279.Crossref 15. Gallant T, Freedman MH, Vellend H, Francombe WH. Yersinia sepsis in patients with iron overload treated with deferoxamine . N Engl J Med . 1986;314:1643. 16. Bloomfield SE, Markenson AL, Miller DR, Peterson CM. Lens opacities in thalassemia . J Pediatr Ophthalmol Strabismus . 1978;15:154-156. 17. Olivieri NF, Buncic JR, Chew E, et al. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions . N Engl J Med . 1986;314:869-873.Crossref 18. Polson RJ, Jawed A, Bomford A, Williams R. Treatment of rheumatoid arthritis with desferrioxamine: relation between stores of iron before treatment and side effects . Br Med J . 1985;291:448.Crossref 19. Simon P, Ang KS, Meyrier A, et al. Desferrioxamine, ocular toxicity, and trace metals . Lancet . 1983;2:512-513.Crossref 20. Borgna-Pignatti C, de Stefano P, Broglia AM. Visual loss in patient on high-dose subcutaneous desferrioxamine . Lancet . 1984;1:681.Crossref 21. Rubinstein M, Dupont P, Doppee J-P, et al. Ocular toxicity of desferrioxamine . Lancet . 1985;1: 817-818.Crossref 22. Davies SC, Hungerford JL, Arden GB, et al. Ocular toxicity of high-dose intravenous desferrioxamine . Lancet . 1983;2:181-184.Crossref 23. Lakhanpal V, Schocket SS, Rouben J. Deferoxamine (desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy . Ophthalmology . 1984;91:443-451.Crossref 24. Blake DR, Winyard P, Lune J, et al. Cerebral and ocular toxicity induced by desferrioxamine . QJMed . 1985;219:345-355. 25. de Virgiliis S, Argiolu F, Sanna G, et al. Auditory involvement in thalassaemia major . Acta Haematol (Basel) . 1979;61:209-215.Crossref 26. Guerin A, London G, Marchais S, et al. Acute deafness and desferrioxamine . Lancet . 1985;2:39-40.Crossref 27. Gallant T, Boyden MH, Gallant LA, et al. Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy . Am J Med . 1987;83:1085-1090.Crossref 28. Freedman MH, Boyden M, Taylor M, Skarf B. Neurotoxicity associated with deferoxamine therapy . Toxicology . 1988;49:283-290.Crossref 29. Taylor MJ, Keenan NK, Gallant T, et al. Subclinical VEP abnormalities in patients on chronic deferoxamine therapy: longitudinal studies . Electroencephalogr Clin Neurophysiol . 1987;68: 81-87.Crossref 30. Dunstan CR, Evans RA. Aluminum and renal bone disease in Australia . Kidney Int . 1986;29( (suppl 18) ):65-69. 31. TG, O'Neal MH, Ortega JA, Hyman CB, Platzker ACG. Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program . Pediatrics . 1980;65:1013-1017. 32. Hoyte RW, Scarpa N, Wilmott RW, Cohen A, Schwartz E. Pulmonary function abnormalities in homozygous β-thalassemia . J Pediatr . 1986; 109:452-455.Crossref 33. Cooper DM, Mansell AL, Weiner MA, et al. Low lung capacity and hypoxemia in children with thalassemia major . Am Rev Respir Dis . 1980;121: 639-646. 34. Wasi P, Fucharoen S, Younchaiyud P, Sonakul D. Hypoxemia in thalassemia . Birth Defects . 1982;18:213-217. 35. Allen J, Cooper JR, White DA, Matthay RA. Drug induced pulmonary disease, II: noncytotoxic drugs . Am Rev Respir Dis . 1986;133:488-505. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

Pulmonary Syndrome in Patients With Thalassemia Major Receiving Intravenous Deferoxamine Infusions

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Publisher
American Medical Association
Copyright
Copyright © 1990 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1990.02150290059028
Publisher site
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Abstract

Abstract • Eight patients with transfusion-dependent thalassemia major were given continuous intravenous infusions of the chelator, deferoxamine mesylate, to reduce iron overload. Within 5 to 9 days of starting the infusions, four patients developed a pulmonary syndrome of moderate to life-threatening severity characterized by tachypnea, hypoxemia, and a diffuse interstitial pattern on chest roentgenogram. Pulmonary function studies showed restrictive dysfunction. Lung biopsy showed diffuse abnormalities with alveolar damage, interstitial fibrosis, and inflammation. The inflammatory infiltrate comprised lymphocytes, eosinophils, and mast cells. Exposure of the biopsy specimen to fluorescein-conjugated anti-IgE antibody showed fixation of IgE to the mast cell surface, suggesting a hypersensitivity reaction. Detailed studies failed to identify an infectious agent. The temporal relationship between drug administration and lung disease, and the clinical similarities in the four affected patients, strongly suggested a cause and effect relationship. We recommend that therapy with continuous intravenous infusions of deferoxamine be monitored carefully with respect to pulmonary status. (AJDC. 1990;144:565-569) References 1. Sephton-Smith R. Iron excretion in thalassemia major after administration of chelating agents . Br Med J . 1962;2:1577-1580.Crossref 2. Wolfe L, Sallan D, Nathan DG. Current therapy and new approaches to the treatment of thalassemia major . Ann NY Acad Sci . 1985;445:248-255.Crossref 3. Graziano JH, Markenson A, Miller DR, et al. Chelation therapy in beta-thalassemia major, I: intravenous and subcutaneous deferoxamine . J Pediatr . 1978;92:648-652.Crossref 4. Cohen A, Mizanin J, Schwartz E. High-dose intravenous chelation therapy with deferoxamine . In: Buckner CD, Gale RP, Lucarelli G, eds. Advances and Controversies in Thalassemia Therapy . New York, NY: Alan R. Liss Inc; 1989:125-131. 5. Modell B, Berdoukas V. The Clinical Approach to Thalassemia . New York, NY: Grune & Stratton; 1984. 6. Engle MA, Erlandson M, Smith CH. Late cardiac complications of chronic, severe, refractory anemia with hemochromatosis . Circulation . 1967; 30:698-705.Crossref 7. Lederman HM, Cohen A, Lee JWW, Freedman MH, Gelfand EW. Deferoxamine: a reversible S-phase inhibitor of human lymphocyte proliferation . Blood . 1984;64:748-753. 8. Blatt J, Stitely S. Antineuroblastoma activity of deferoxamine in human cell lines . Cancer Res . 1987;47:1749-1750. 9. Estrov Z, Cohen A, Gelfand EW, Freedman MH. Cytotoxicity in vitro of deferoxamine on human marrow hematopoietic progenitors . Toxicology In Vitro . 1988;2:131-134.Crossref 10. Estrov Z, Tawa A, Wang X, et al. In vitro and in vivo effects of deferoxamine in neonatal acute leukemia . Blood . 1987;69:757-761. 11. Kaplinsky C, Estrov Z, Freedman MH, Gelfand EW, Cohen A. Effect of deferoxamine on DNA synthesis, DNA repair, cell proliferation, and differentiation on HL-60 cells . Leukemia . 1987;1:437-441. 12. Miller KB, Rosenwasser LJ, Bessette JM, et al. Rapid desensitization for deferoxamine anaphylactic reaction . Lancet . 1981;1:1059.Crossref 13. Walker JA, Sherman RA, Eisinger RP. Thrombocytopenia associated with intravenous desferrioxamine . Am J Kidney Dis . 1985;6:254-256.Crossref 14. Batey R, Scott J, Jain S, Sherlock S. Acute renal insufficiency occurring during intravenous desferrioxamine therapy . Scand J Haematol . 1979;22:277-279.Crossref 15. Gallant T, Freedman MH, Vellend H, Francombe WH. Yersinia sepsis in patients with iron overload treated with deferoxamine . N Engl J Med . 1986;314:1643. 16. Bloomfield SE, Markenson AL, Miller DR, Peterson CM. Lens opacities in thalassemia . J Pediatr Ophthalmol Strabismus . 1978;15:154-156. 17. Olivieri NF, Buncic JR, Chew E, et al. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions . N Engl J Med . 1986;314:869-873.Crossref 18. Polson RJ, Jawed A, Bomford A, Williams R. Treatment of rheumatoid arthritis with desferrioxamine: relation between stores of iron before treatment and side effects . Br Med J . 1985;291:448.Crossref 19. Simon P, Ang KS, Meyrier A, et al. Desferrioxamine, ocular toxicity, and trace metals . Lancet . 1983;2:512-513.Crossref 20. Borgna-Pignatti C, de Stefano P, Broglia AM. Visual loss in patient on high-dose subcutaneous desferrioxamine . Lancet . 1984;1:681.Crossref 21. Rubinstein M, Dupont P, Doppee J-P, et al. Ocular toxicity of desferrioxamine . Lancet . 1985;1: 817-818.Crossref 22. Davies SC, Hungerford JL, Arden GB, et al. Ocular toxicity of high-dose intravenous desferrioxamine . Lancet . 1983;2:181-184.Crossref 23. Lakhanpal V, Schocket SS, Rouben J. Deferoxamine (desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy . Ophthalmology . 1984;91:443-451.Crossref 24. Blake DR, Winyard P, Lune J, et al. Cerebral and ocular toxicity induced by desferrioxamine . QJMed . 1985;219:345-355. 25. de Virgiliis S, Argiolu F, Sanna G, et al. Auditory involvement in thalassaemia major . Acta Haematol (Basel) . 1979;61:209-215.Crossref 26. Guerin A, London G, Marchais S, et al. Acute deafness and desferrioxamine . Lancet . 1985;2:39-40.Crossref 27. Gallant T, Boyden MH, Gallant LA, et al. Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy . Am J Med . 1987;83:1085-1090.Crossref 28. Freedman MH, Boyden M, Taylor M, Skarf B. Neurotoxicity associated with deferoxamine therapy . Toxicology . 1988;49:283-290.Crossref 29. Taylor MJ, Keenan NK, Gallant T, et al. Subclinical VEP abnormalities in patients on chronic deferoxamine therapy: longitudinal studies . Electroencephalogr Clin Neurophysiol . 1987;68: 81-87.Crossref 30. Dunstan CR, Evans RA. Aluminum and renal bone disease in Australia . Kidney Int . 1986;29( (suppl 18) ):65-69. 31. TG, O'Neal MH, Ortega JA, Hyman CB, Platzker ACG. Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program . Pediatrics . 1980;65:1013-1017. 32. Hoyte RW, Scarpa N, Wilmott RW, Cohen A, Schwartz E. Pulmonary function abnormalities in homozygous β-thalassemia . J Pediatr . 1986; 109:452-455.Crossref 33. Cooper DM, Mansell AL, Weiner MA, et al. Low lung capacity and hypoxemia in children with thalassemia major . Am Rev Respir Dis . 1980;121: 639-646. 34. Wasi P, Fucharoen S, Younchaiyud P, Sonakul D. Hypoxemia in thalassemia . Birth Defects . 1982;18:213-217. 35. Allen J, Cooper JR, White DA, Matthay RA. Drug induced pulmonary disease, II: noncytotoxic drugs . Am Rev Respir Dis . 1986;133:488-505.

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: May 1, 1990

References