Abstract
The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P=0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P=0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P<0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT (P=0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G>A may be a new possible predictive marker for outcome in childhood ALL.
| Original language | English |
|---|---|
| Journal | Pharmacogenomics Journal |
| Volume | 15 |
| Issue number | 4 |
| Pages (from-to) | 372-9 |
| Number of pages | 8 |
| ISSN | 1470-269X |
| DOIs | |
| Publication status | Published - 25 Aug 2015 |
Keywords
- Acute Disease
- Adolescent
- Antineoplastic Agents
- Bone Marrow Diseases
- Child
- Child, Preschool
- Denmark
- Drug-Induced Liver Injury
- Genotype
- Haplotypes
- Humans
- Infant
- Male
- Methotrexate
- P-Glycoproteins
- Polymorphism, Genetic
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Predictive Value of Tests
- Recurrence
- Risk Assessment
- Treatment Outcome
