On the limitation of 6-tioguaninenucleotide monitoring during tioguanine treatment.
BACKGROUND
Tioguanine (thioguanine) has been proposed as a rescue thiopurine for azathioprine or mercaptopurine intolerant inflammatory bowel disease patients. The use of tioguanine leads to high 6-tioguaninenucleotide (6-thioguaninenucleotide) levels in red blood cells but, contra-intuitively, these have yet not been associated with an increased risk of myelotoxicity.


OBJECTIVE
To assess the role of 6-tioguaninenucleotide concentrations in developing myelotoxicity during tioguanine treatment.


METHODS
Database analysis of 25 patients treated with tioguanine. Clinical findings and laboratory parameters were related to 6-tioguaninenucleotide levels.


RESULTS
One patient developed a myelodepression (21 mg TG/day for 3 months and 6-tioguaninenucleotide 714 pmol/8 x 10(8) red blood cells). 6-Tioguaninenucleotide levels varied greatly between individuals (mean 6-tioguaninenucleotide level 621 pmol/8 x 10(8) red blood cells, s.d. 340 pmol/8 x 10(8) red blood cells and range 34-1653 pmol/8 x 10(8) red blood cells). The TG dosages (mean 20.6 mg/day and median 20 mg/day) did not correlate with 6-tioguaninenucleotide levels (r = 0.31, N.S.). High 6-tioguaninenucleotide levels (>450 pmol/8 x 10(8) red blood cells) did not effect haemoglobin concentrations (mean 8 mmol/L), peripheral leucocyte (mean 7.5 x 10(9)/L) or platelet counts (mean 298 x 10(9)/L). No correlations were established between laboratory parameters, type of disease and 6-tioguaninenucleotide level.


CONCLUSIONS
High 6-tioguaninenucleotide levels in erythrocytes (>450 pmol/8 x 10(8)) during TG treatment compared to azathioprine or mercaptopurine treatment are not indicative for (developing) myelotoxicity.
de Boer
N K H
NK
Gastroenterology and Hepatology, VU University Medical Centre, The Netherlands.
de Graaf
P
P
Wilhelm
A J
AJ
Mulder
C J J
CJ
van Bodegraven
A A
AA
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control; D002446:Celiac Disease / Q000188:drug therapy* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019693:Hepatitis, Autoimmune / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D013866:Thioguanine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine