Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia

Abstract

Durable remissions in children with acute lymphoblastic leukemia (ALL) require about a 2-year maintenance therapy phase that includes daily self-, parent-, or caregiver-administered oral 6-mercaptopurine (6MP).¹ This drug exerts cytotoxic effects, in part, through conversion to thioguanine nucleotide metabolites (TGN) that are incorporated into DNA with resultant damage.^2-4 Systemic exposure to 6MP (as measured by erythrocyte TGN levels) is determined by the dose prescribed by the clinician, adherence by the patient or parent to the prescribed dose, absorption of 6MP from the gastrointestinal tract, and its metabolism by enzymes such as thiopurine methyltransferase (TPMT).