The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia

Abstract

High levels of 6MMP are associated with symptomatic hypoglycemia which may be mitigated by switching to morning or twice daily 6-MP dose administration.

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

“…Hypoglycemic episodes during fasting157–160 have been associated with high levels of methylated 6MP metabolites 161. It can be counteracted by evening meals with slowly absorbed carbohydrates, by administration of rapidly absorbed carbohydrates (eg, apple juice) in case of symptoms, or by shifting to morning dosage.…”

“…It can be counteracted by evening meals with slowly absorbed carbohydrates, by administration of rapidly absorbed carbohydrates (eg, apple juice) in case of symptoms, or by shifting to morning dosage. The latter reduces Ery-MeMP levels but the impact on relapse rate is unknown 161. Few patients develop symptoms of hypoglycemia such as severe nausea, itching, or malaise to a degree that requires dose reductions.…”

Allopurinol Use During Maintenance Therapy for Acute Lymphoblastic Leukemia Avoids Mercaptopurine-related Hepatotoxicity

“…25,26 Interestingly, elevated levels of 6-MMPN was also associated with symptomatic hypoglycemia and switching from evening administration to morning administration decreases 6-MMPN while preserving 6-TGN levels. 27 How changing the timing of MP administration changes the metabolism 6-MP is not clear. Thus, further work on the mechanism of how allopurinol affects 6-MP metabolism is needed to better understand this effect to better incorporate this therapy into standard ALL treatment protocols.…”

“…Another scenario where allopurinol could be helpful is in patients with symptomatic hypoglycemia as allopurinol will lower 6-MMPN levels without having to change the timing of 6-MP administration. 27 However, 6-MMPN may also play a role in the antileukemic effect of MP by inhibiting de novo purine synthesis although allopurinol by itself also inhibits de novo purine synthesis. 28 Combination therapy with allopurinol needs to be incorporated into future clinical trials to ensure that long-term outcomes are not affected by this therapy.…”

Effect of Bcl-2-siRNA on proliferation and apoptosis of pediatric acute B lymphoblastic leukemia (A-BLL) cells

“…The VDLD therapeutic regime that has been used clinically is the first-line approach for treatment of A-BLL. However, recent research has indicated an increase in the rate of resistance to chemotherapeutic drugs; in addition, these drugs impart severe toxic and side effects, thereby restricting the clinical use of this therapeutic regime (Brackett et al, 2014;Melachuri et al, 2014).…”