PMID- 9695957
OWN - NLM
STAT- MEDLINE
DCOM- 19980818
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 102
IP  - 2
DP  - 1998 Jul
TI  - Thioguanine versus mercaptopurine for therapy of childhood lymphoblastic 
      leukaemia: a comparison of haematological toxicity and drug metabolite 
      concentrations.
PG  - 439-43
AB  - As a prelude to a nationwide randomized trial of thioguanine (TG) versus 
      mercaptopurine (MP) for childhood lymphoblastic leukaemia we compared a pilot 
      group of 23 children taking TG with a matched group taking MP. We assessed drug 
      tolerance based on haematological toxicity and measured erythrocyte (RBC) 
      concentrations of thioguanine nucleotides (TGN). The median tolerated dose of TG 
      was 30 mg/m2 compared to 55 mg/m2 for MP. There was no difference in the pattern 
      of anaemia or neutropenia between the two groups, but dose-limiting 
      thrombocytopenia was more evident in the TG children (P< 0.001), four of whom had 
      a decrease in platelet count to <20 x 10(9)/l compared to only one on MP. The 
      median RBC TGN concentration for those on 40 mg/m2 TG was 1726 pmol/8 x 10(8) 
      RBCs compared with 308 pmol/8 x 10(8) RBCs for those on 75 mg/m2 MP (P< 0.0001). 
      There was an inverse correlation between RBC TGNs and neutrophil count in the MP 
      group but not in those on TG. No correlation between metabolite concentration and 
      thrombocytopenia was found in either group. These results provide further 
      evidence that TG has a selective effect on platelets. They also showed that RBC 
      TGN were, on average, 5-fold higher in those taking TG but did not obviously 
      relate to myelotoxicity as found in children on MP. The higher concentrations 
      seen may partly reflect the erythrocyte's ability to metabolize TG directly to 
      TGN by pathways not open to MP.
FAU - Lancaster, D L
AU  - Lancaster DL
AD  - Department of Paediatric Oncology, St Bartholomew's and the Royal London School 
      of Medicine and Dentistry, St Bartholomew's Hospital, West Smithfield.
FAU - Lennard, L
AU  - Lennard L
FAU - Rowland, K
AU  - Rowland K
FAU - Vora, A J
AU  - Vora AJ
FAU - Lilleyman, J S
AU  - Lilleyman JS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Nucleotides)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
SB  - IM
MH  - Adolescent
MH  - Antimetabolites, Antineoplastic/adverse effects/metabolism/*therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Humans
MH  - Infant
MH  - Lymphocyte Count
MH  - Male
MH  - Mercaptopurine/adverse effects/metabolism/*therapeutic use
MH  - Neutropenia/chemically induced
MH  - Neutrophils
MH  - Nucleotides/metabolism
MH  - Platelet Count
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/metabolism
MH  - Thioguanine/adverse effects/metabolism/*therapeutic use
MH  - Thrombocytopenia/chemically induced
EDAT- 1998/08/08 00:00
MHDA- 1998/08/08 00:01
CRDT- 1998/08/08 00:00
PHST- 1998/08/08 00:00 [pubmed]
PHST- 1998/08/08 00:01 [medline]
PHST- 1998/08/08 00:00 [entrez]
AID - 10.1046/j.1365-2141.1998.00812.x [doi]
PST - ppublish
SO  - Br J Haematol. 1998 Jul;102(2):439-43. doi: 10.1046/j.1365-2141.1998.00812.x.