title: Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide.
abstract: Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.
authors.affiliation: 1st Department of Internal Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishitsuka
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shirahashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iwao
authors.forename: Mikiko
authors.initials: M
authors.lastname: Shishime
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Syuji
authors.initials: S
authors.lastname: Hara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects*; D001853:Bone Marrow / Q000473:pathology*; D001855:Bone Marrow Diseases / Q000139:chemically induced*; D005334:Fever / Q000139:chemically induced; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009336:Necrosis; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects*; D010198:Pancytopenia / Q000139:chemically induced; D012074:Remission Induction
chemical_list: D001152:Arsenicals; D010087:Oxides; D015122:Mercaptopurine; D000077237:Arsenic Trioxide; D006918:Hydroxyurea