title: Mitochondrial myopathy caused by arsenic trioxide therapy.
abstract: Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO. Three months after ATO therapy withdrawal, the patient was unable to walk without assistance and skeletal muscle studies showed a myopathy with abundant cytoplasmic lipid droplets, decreased activities of the mitochondrial respiratory chain complexes, multiple mitochondrial DNA (mtDNA) deletions, and increased muscle arsenic content. Six months after ATO treatment was interrupted, the patient recovered normal strength, lipid droplets had decreased in size and number, respiratory chain complex activities were partially restored, but multiple mtDNA deletions and increased muscle arsenic content persisted. ATO therapy may provoke a delayed, severe, and partially reversible mitochondrial myopathy, and a long-term careful surveillance for muscle disease should be instituted when ATO is used in patients with APL.
authors.affiliation: Département de Neurologie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre,1 Avenue Molière, Strasbourg Cedex, France. andoni.echaniz-laguna@chru-strasbourg.fr
authors.forename: Andoni
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.forename: Aurélien
authors.initials: A
authors.lastname: Benoilid
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vinzio
authors.forename: Luc-Matthieu
authors.initials: LM
authors.lastname: Fornecker
authors.forename: Béatrice
authors.initials: B
authors.lastname: Lannes
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Goullé
authors.forename: Frank
authors.initials: F
authors.lastname: Broly
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Mousson de Camaret
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy*; D008931:Mitochondria, Muscle / Q000187:drug effects; D017240:Mitochondrial Myopathies / Q000139:chemically induced* / Q000473:pathology; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects*; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide