title: Dose-adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal failure.
abstract: OBJECTIVE
  To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF.
  
  
  METHODS
  Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d.
  
  
  RESULTS
  Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months.
  
  
  CONCLUSIONS
  The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function.
authors.affiliation: Department of Medicine, St Vincent's Hospital, Melbourne University, Fitzroy, Vic., Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Firkin
authors.affiliation: Department of Haematology, St George Hospital, Kogarah, NSW, Australia.
authors.forename: Fernando
authors.initials: F
authors.lastname: Roncolato
authors.affiliation: Department of Haematology, Austin Hospital, Heidelberg, Vic., Australia.
authors.forename: Wai Khoon
authors.initials: WK
authors.lastname: Ho
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000009:adverse effects; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000209:etiology / Q000628:therapy; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide
keywords: acute promyelocytic leukaemia; arsenic blood level monitoring; arsenic trioxide; chronic renal failure; dosage adjustment