title: Biochemical, radiologic, ultrastructural, and genetic evaluation of iron overload in acute leukemia and iron-chelation therapy.
abstract: Iron overload in hereditary hemochromatosis and hematologic malignancy has unfavorable effects on morbidity. Herein, 53 children (age 108.4±58.3 mo, 25 girls and 28 boys) with acute myeloblastic and lymphoblastic leukemia, who received 4 different chemotherapy protocols, were evaluated for iron overload throughout chemotherapy. Iron overload arose: (1) before chemotherapy, which was dependent on neither chemotherapy nor packed red blood cell transfusions and (2) after chemotherapy, which was dependent on the duration and nature of chemotherapy and partially on transfusion of packed red blood cells. Iron overload was documented in 75% of patients with a ferritin level >1000 ng/mL, by liver and heart magnetic resonance imaging, and they were administered iron-chelation therapy with success. Three of 10 radiologically iron-overloaded patients were heterozygous for H63D mutation. Aminolevulinic acid and porphobilinogen levels were normal. Light microscopic examination of the bone marrow revealed increased iron granules in erythroblasts, platelets, and megakaryocytes, iron-laden macrophages, free iron in the matrix, dyshematopoiesis, and apoptotic cells. Electron microscopic examination revealed iron-laden secondary lysosomes and autolysosomes in normoblasts and iron-laden primary granules in promyelocytes, irrelevant to the ferritin level, implying autophagia due to chemotherapy as a source of the excess iron. We think that iron overload, which is an important complication of acute leukemia, should be evaluated separately from "transfusion overload," and the management principles specific to leukemia should be implemented.
authors.affiliation: Units of *Pediatric Hematology ¶Radiology, Ankara Oncology Training and Research Hospital †Department of Radiology, Hacettepe University Faculty of Medicine §Department of Histology Embryology, Ankara University Faculty of Medicine ∥Department of Medical Genetics, Başkent University Faculty of Medicine #Ankara Occupational Diseases Hospital, Ankara ‡Unit of Pediatric Hematology, Şişli Etfal Children's Hospital, İstanbul, Turkey.
authors.forename: Lale
authors.initials: L
authors.lastname: Olcay
authors.forename: Tuncay
authors.initials: T
authors.lastname: Hazirolan
authors.forename: Yildiz
authors.initials: Y
authors.lastname: Yildirmak
authors.forename: Esra
authors.initials: E
authors.lastname: Erdemli
authors.forename: Yunus Kasim
authors.initials: YK
authors.lastname: Terzi
authors.forename: Kemal
authors.initials: K
authors.lastname: Arda
authors.forename: Seda
authors.initials: S
authors.lastname: Oztürkmen
authors.forename: Arzu
authors.initials: A
authors.lastname: Akyay
authors.forename: Meriç
authors.initials: M
authors.lastname: Kaymak-Cihan
authors.forename: Zafer
authors.initials: Z
authors.lastname: Biçakçi
authors.forename: Ceylan
authors.initials: C
authors.lastname: Bal
mesh_terms: D000293:Adolescent; D000622:Aminolevulinic Acid / Q000097:blood; D001853:Bone Marrow / Q000378:metabolism / Q000648:ultrastructure; D001854:Bone Marrow Cells / Q000378:metabolism / Q000648:ultrastructure; D002648:Child; D005260:Female; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007501:Iron / Q000097:blood; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D020125:Mutation, Missense; D011162:Porphobilinogen / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D007502:Iron Chelating Agents; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D005293:Ferritins; D007501:Iron