[Allelic variants of TPMT and the risk of leucopenia and neutropenia in patients treated for acute leukaemia].
OBJECTIVE
The objective of this study was to analyse the influence of TPMT genetic polymorphism on the occurrence of therapeutical adverse effects such as hematological disorders, leucopenia and neutropenia after thiopurines administration.


METHODS
The examined group consisted of 210 patients (121 boys, 89 girls) aged between 1 and 18 (median age 7 years, average age 8 years, SD+/-5.32) treated for leukaemia (acute lymphoblastic leukaemia ALL: n=167; acute myeloblastic leukaemia AML: n=43). Analysis of treatment adverse reactions in every child was performed according to the WHO toxicity scale, during the entire length of observation period and in particular stages (6 stages).


RESULTS
Analysis of changes in selected blood count parameters in the whole treatment period in the acute leukaemia group indicated that in the TPMT *2, *3A or *3C polymorphism carriers' group there is a statistically significant decrease in the white blood cell count (p=0.0025) and in the neutrophil count (p=0.019). Detailed assessment in particular treatment periods indicated that increased leukopenia in TPMT heterozygotes occurred significantly more frequently only in early re-induction period (p=0.012).


CONCLUSIONS
Thiopurines administration is related to the increase in hemato-oncological treatment toxicity in TPMT heterozygotes.
Niedzielska
Ewa
E
Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej Akademii Medycznej we Wrocławiu, Wrocław. eniedzielska@poczta.onet.pl
Niedzielska
Małgorzata
M
Chybicka
Alicja
A
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007970:Leukopenia / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D009503:Neutropenia / Q000139:chemically induced / Q000235:genetics*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology*
D000964:Antimetabolites, Antineoplastic; D008780:Methyltransferases; C022745:thiopurine methyltransferase