Pathology tests database

Sample and container requirements

EDTA Whole Blood

Minimum volume required

3 mL whole blood

Special requirements

Do not centrifuge.

Patient preparation

None

Sample viability

Turnaround time

7 days

Reference range

For children and young adults with ALL, please refer to your protocol directed guidance. The guidelines below apply to azathioprine/6-mercaptopurine immunosuppression. TGN therapeutic range 235 – 450 pmol/8 x 10E8 RBC TGN <235: TGN below the therapeutic range. Question adherence. Consider dose incrementing if the patient is adherent. If the MeMP/TGN ratio is >11, consider changing therapy to 25% of the target thiopurine dose with 100 mg allopurinol. TGN 235 – 450: TGN within the therapeutic range. The patient is appropriately dosed. If the patient is not responding to therapy, consider alternative immunosuppressant therapies. Where MeMP > 5700, there is an increased risk of hepatotoxicity, in such patients consider changing therapy to 25% of the target thiopurine dose with 100mg allopurinol. TGN >450: TGN above the therapeutic range. Dose reduction is advisable if TGN levels are above 550, depending on clinical situation. If patient is not responding to therapy, consider alternative immunosuppressant therapies. For 6MMP, therapeutic range is <5700 pmol/8 x 108 RBC Repeat TGN measurement 4 – 6 weeks after any change in therapy.

Clinical guidance

Thiopurine metabolite testing measures the end-products of two major metabolic pathways of azathioprine and mercaptopurine. Measurement of these metabolites can help assess treatment efficacy, adherence and the risk of toxicity. 6-Thioguanine nucleotides (6-TGN) are the end-products of the active metabolic pathway. Within the therapeutic range: associated with good treatment efficacy. Below the therapeutic range: may indicate inadequate drug exposure and reduced efficacy. Above the therapeutic range: associated with an increased risk of myelosuppression. 6-Methylmercaptopurine (6-MMP) is the end-product of the methylation pathway. High concentrations: are associated with an increased risk of hepatotoxicity. Clinical Applications Thiopurine metabolite testing may be useful in the following situations: 1. Suspected non-response Assess whether the patient is under-dosed. Assess adherence to therapy. Identify altered thiopurine metabolism. 2. Suspected toxicity Myelosuppression may be associated with elevated 6-TGN concentrations. Hepatotoxicity may be associated with elevated 6-MMP concentrations. 3. Optimising therapy Support dose adjustment. Identify patients with preferential methylation ("shunters"), characterised by high 6-MMP concentrations and relatively low 6-TGN concentrations. Guide consideration of alternative treatment strategies (e.g. low-dose thiopurine with allopurinol where clinically appropriate).

Notes