Determinants of cerebrospinal fluid arsenic concentration in patients with acute promyelocytic leukemia on oral arsenic trioxide therapy.
The extent of and factors controlling arsenic penetration into the central nervous system (CNS) remain unclear. Elemental arsenic levels in 67 paired cerebrospinal fluid (CSF) and plasma samples from 9 patients with acute promyelocytic leukemia (APL) on oral arsenic trioxide (As2O3), obtained during intrathecal chemotherapy (treatment of CNS APL, n = 6; prophylaxis, n = 3) were measured. Median arsenic levels of CSF and plasma were 95.8 nmol/L (range, 3.5-318.9 nmol/L) and 498.9 nmol/L (range, 36.3-1892.8 nmol/L). As a group, CSF and plasma arsenic was linearly correlated (P < .001), with CSF at 17.7% the plasma level. The CSF/plasma arsenic ratio, which reflected the arsenic CSF penetration efficiency, varied significantly in individual patients (P < .001). Repeated intrathecal chemotherapy and presence of blasts in CSF did not affect the CSF/plasma arsenic ratio. Plasma arsenic was the only significant determinant of CSF arsenic levels. CSF arsenic was present at therapeutically meaningful levels, implying that As2O3 therapy might be beneficial in CNS APL.
Au
Wing-Yan
WY
Department of Medicine, Queen Mary Hospital, Hong Kong.
Tam
Sidney
S
Fong
Bonnie M
BM
Kwong
Yok-Lam
YL
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001151:Arsenic / Q000097:blood / Q000134:cerebrospinal fluid*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012008:Recurrence
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D003561:Cytarabine; D001151:Arsenic; D000077237:Arsenic Trioxide; D008727:Methotrexate