TPMT/NUDT15 genotyping for thiopurines in Acute Lymphoblastic Leukaemia (Test codes M91.80 & M91.81)
Genetic variants in either the TPMT or NUDT15 gene can affect the ability to metabolise thiopurines such as 6-mercaptopurine, causing serious and potentially fatal haematological toxicity. Currently commissioned genotyping tests consider patients receiving thiopurines for the treatment of acute lymphoblastic leukaemia (ALL) only. Despite a ‘normal’ test result, patients may still experience toxicity due to rare genetic variants that have not been detected, or other clinical factors.
More information
Test eligibility
Patients diagnosed with Acute Lymphoblastic Leukaemia planned to receive thiopurine chemotherapy.
Test order form
Paediatric ALL patients within the South West GMS region will have TPMT/NUDT15 genotyping undertaken on a reflex basis, following an ALL diagnosis
Test requests for paediatric ALL patients from outside the SW GMS region and adult ALL patients should be completed using the SW GMS test request form:
This should be completed in full & include the test indication ‘TPMT/NUDT15 genotyping for ALL patient prior to thiopurine treatment’.
Alternatively, local test request forms with the equivalent information are acceptable.
Sample and transport information
Please ensure that the patient identity has been verified before taking the sample. • The sample should be labelled with at least 3 patient identifiers including the patient’s name & date of birth. • Please send the completed referral form and the labelled patient sample (2-4ml of EDTA blood) to the designated Genomics Laboratory Hub (address below) or send via the appropriate SIHMDS network.
South West Genomics Laboratory Hub Bristol Genetics Laboratory Southmead Hospital Westbury-on-Trym Bristol BS10 5NB
Transportation instructions
· Samples should be sent at room temperature. If there is a delay in sending the sample can be refrigerated at +4 degree Celsius for a few days without affecting quality.
· The sample container should be leak-proof and must be placed in a transparent sample bag with the paperwork attached but not in the same compartment as the container. The outer sample packaging must comply with PI 650 for category B substances. The package should be clearly labelled ‘diagnostic specimen UN3373’.
· Samples should be sent to the laboratory via your local hospital transport services or directly using first class via the Royal Mail postal services or via the appropriate SIHMDS network.
For full instructions, please visit the sample requirements and transport information page
Test Methodology
LAMP coupled melt-curve analysis is used to genotype the common TPMT variants (TPMT*2,TPMT*3A, TPMT*3B, TPMT*3C) and the most common NUDT15 variants (NUDT15*3 & NUDT15*9).
Results and turnaround times
Reports will be returned by email within 14 days as a pdf-document. • Report recipient details (name, job title and email address) should be specified on the referral form. • Alternatively, the GLH will manage a list of recipients for your region; contact SWGLHcancer@nbt.nhs.uk at the SWGLH to discuss what information is required to set this up.