Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia
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 intrace...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | EJC Paediatric Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772610X23000260 |
| _version_ | 1797345883782643712 |
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| author | Lauryna Aukstikalne Ignas Klejus Maria Thastrup Tadas Zvirblis Kjeld Schmiegelow Goda Elizabeta Vaitkeviciene Linea Natalie Toksvang |
| author_facet | Lauryna Aukstikalne Ignas Klejus Maria Thastrup Tadas Zvirblis Kjeld Schmiegelow Goda Elizabeta Vaitkeviciene Linea Natalie Toksvang |
| author_sort | Lauryna Aukstikalne |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T11:24:14Z |
| format | Article |
| id | doaj.art-e7f609ee25ab40a2bea114805167edb8 |
| institution | Directory Open Access Journal |
| issn | 2772-610X |
| language | English |
| last_indexed | 2024-03-08T11:24:14Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EJC Paediatric Oncology |
| spelling | doaj.art-e7f609ee25ab40a2bea114805167edb82024-01-26T05:38:43ZengElsevierEJC Paediatric Oncology2772-610X2023-12-012100028Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemiaLauryna Aukstikalne0Ignas Klejus1Maria Thastrup2Tadas Zvirblis3Kjeld Schmiegelow4Goda Elizabeta Vaitkeviciene5Linea Natalie Toksvang6Vilnius University Hospital Santaros Klinikos Department of Biomedical Research, Vilnius, LithuaniaVilnius University Hospital Santaros Klinikos Family Medicine Center, Vilnius, LithuaniaDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, DenmarkDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, LithuaniaDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, DenmarkVilnius University Faculty of Medicine, Clinic of Children Diseases, Institute of Clinical medicine, Vilnius, Lithuania; Vilnius University Hospital Santaros Klinikos, Center for Pediatric Oncology and Hematology, Vilnius, Lithuania; Correspondence to: Vilnius University Faculty of Medicine, Institute of Clinical medicine, Clinic of Children Diseases, Vilnius, Lithuania.Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, DenmarkBackground: 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.http://www.sciencedirect.com/science/article/pii/S2772610X23000260LeukemiaAcuteLymphoblasticMaintenance therapy6-mercaptopurineRelapse |
| spellingShingle | Lauryna Aukstikalne Ignas Klejus Maria Thastrup Tadas Zvirblis Kjeld Schmiegelow Goda Elizabeta Vaitkeviciene Linea Natalie Toksvang Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia EJC Paediatric Oncology Leukemia Acute Lymphoblastic Maintenance therapy 6-mercaptopurine Relapse |
| title | Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia |
| title_full | Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia |
| title_fullStr | Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia |
| title_full_unstemmed | Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia |
| title_short | Erythrocyte-incorporated 6-mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia |
| title_sort | erythrocyte incorporated 6 mercaptopurine metabolite levels are not affected by recent drug administration during maintenance therapy for childhood acute lymphoblastic leukemia |
| topic | Leukemia Acute Lymphoblastic Maintenance therapy 6-mercaptopurine Relapse |
| url | http://www.sciencedirect.com/science/article/pii/S2772610X23000260 |
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