The purpose of this study was to assess the efficacy and safety of individualized treatment of 6-mercaptopurine (6-MP) in Chinese children with acute lymphoblastic leukemia, and to investigate the dose-concentration-response (DER) relationship between thiopurine metabolites and adverse events. The individualized administration of 6-MP was established in Chinese children with acute lymphoblastic leukemia.
To inflict minimal pain on the child contributing blood samples, opportunistic sampling design was chosen to collect pharmacokinetic samples.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
82
6-mercaptopurine was administered orally to patients once daily.
The initial dose is 50mg/m2. The dose was adjusted according to white blood cells.
The initial dose is determined according to the genotypes of patients combined with Clinical Pharmacogenetics Implementation Consortium (CPIC). The dose was adjusted according to white blood cells, genotypes and the concentrations of 6-TGN in red blood cells.
State Key Laboratory of Experimental Haematology, Department of Paediatric Haematology, Institute of Haematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tanjin, Tianjin Municipality, China
leukopenia
Leukopenia was graded by common toxicity criteria as follows: Grade 3, 1.0-2.0 × 109/L, and Grade 4, \< 1.0 × 109/L.
Time frame: 6 weeks
thiopurine-induced leukopenia
Resolution of leukopenia was determined after 6-MP dose reduction or discontinuation, both in the absence of other apparent causes for the leukopenia or its disappearance.
Time frame: 6-weeks
hepatotoxicity
Hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine transaminase (ALT) levels 2-fold above the upper limit without cytolysis.
Time frame: 6 weeks
6-thioguanine nucleotides (6-TGN) concentrations in erythrocytes.
Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design.
Time frame: 3 months
6-methylmercaptopurine nucleotides (6-MMPN) concentrations in erythrocytes.
Peripheral blood samples were obtained from steady-state plasma concentrates by opportunistic sampling design.
Time frame: 3 months
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