Abstract
Background
Childhood acute lymphoblastic leukemia (ALL) maintenance therapy with oral 6-mercaptopurine (6-MP) and methotrexate prevents leukemic relapse by acting against residual lymphoblasts. Non-adherence to oral maintenance therapy significantly increases ALL relapse risk. The levels of intracellular 6-MP metabolites erythrocyte incorporated (ery-) thioguanine nucleotides (ery-TGN) and methylated 6-MP metabolites (ery-MeMP) can be used to evaluate adherence to 6-MP, however, little is known on their short-term pharmacokinetics. The aim of this study was to assess the changes between trough levels and the levels at 2-hours after 6-MP intake when the 6-MP levels in plasma is expected to have peaked.
Materials and methods
Ten ALL patients with stable 6-MP dose were prospectively included. Two blood samples were collected for ery-TGN and ery-MeMP analysis (before 6-MP intake and 2 h after).
Results
The median trough ery-TGN was 173 (range 126–299) nmol/mmol hemoglobin (HGB), and 2 h after 6-MP intake the median level was 175 (range 120–293) nmol/mmol HGB. For ery-MeMP, the median trough and 2 h-concentrations were 9 239 (range 1 278–19 645) nmol/mmol HGB and 9 216 (range 1 215–19 519) nmol/mmol HGB, respectively. The median absolute percentual change for both ery-TGN and ery-MeMP were not statistically different from 0, p = 0.28 and p = 0.06, respectively.
Conclusions
Intracellular 6-MP metabolites, ery-MeMP and ery-TGN, remain stable 2 h after oral 6-MP intake in patients with a stable 6-MP dose. This data support that blood samples may be used to assess patient adherence irrespective of the timing of 6-MP intake.
Childhood acute lymphoblastic leukemia (ALL) maintenance therapy with oral 6-mercaptopurine (6-MP) and methotrexate prevents leukemic relapse by acting against residual lymphoblasts. Non-adherence to oral maintenance therapy significantly increases ALL relapse risk. The levels of intracellular 6-MP metabolites erythrocyte incorporated (ery-) thioguanine nucleotides (ery-TGN) and methylated 6-MP metabolites (ery-MeMP) can be used to evaluate adherence to 6-MP, however, little is known on their short-term pharmacokinetics. The aim of this study was to assess the changes between trough levels and the levels at 2-hours after 6-MP intake when the 6-MP levels in plasma is expected to have peaked.
Materials and methods
Ten ALL patients with stable 6-MP dose were prospectively included. Two blood samples were collected for ery-TGN and ery-MeMP analysis (before 6-MP intake and 2 h after).
Results
The median trough ery-TGN was 173 (range 126–299) nmol/mmol hemoglobin (HGB), and 2 h after 6-MP intake the median level was 175 (range 120–293) nmol/mmol HGB. For ery-MeMP, the median trough and 2 h-concentrations were 9 239 (range 1 278–19 645) nmol/mmol HGB and 9 216 (range 1 215–19 519) nmol/mmol HGB, respectively. The median absolute percentual change for both ery-TGN and ery-MeMP were not statistically different from 0, p = 0.28 and p = 0.06, respectively.
Conclusions
Intracellular 6-MP metabolites, ery-MeMP and ery-TGN, remain stable 2 h after oral 6-MP intake in patients with a stable 6-MP dose. This data support that blood samples may be used to assess patient adherence irrespective of the timing of 6-MP intake.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 100028 |
| Tidsskrift | EJC Paediatric Oncology |
| Vol/bind | 2 |
| Antal sider | 5 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:This work is part of Childhood Oncology Network Targeting Research, Organisation & Life Expectancy (CONTROL) and supported by Danish Cancer Society (R-257-A14720) and the Danish Childhood Cancer Foundation (2019-5934). The preparation of the study was supported by Lithuanian Childhood Cancer Foundation \u2018Rugute\u2019.
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© 2023