Response MRP 4 gene polymorphisms and treatment response in adult ALL

phisms modulating dose intensity of these drugs. Using this approach, we did not find any important MRDpredisposing MRP4 genotype. In addition, comparisons of KaplanMeier estimates did not detect significant differences in EFS for patients with different MRP4 genotypes. At most we observed an oppositional trend compared with the study of Ansari toward a poorer EFS for carriers of TC-1393 and AC/CC934 (group 1),1 whereas patients with TT-1393 and AC934 (group 3)1 tended toward a better EFS (Figure 1). The discrepancy cannot be ascribed to differences in genotype distribution between the 2 ALL series (frequencies in this study vs Ansari et al: T-1393C: TT 88.7% vs 88.3%, TC 11.1% vs 11.7%, CC 0.2% vs 0.0%; C934A CC 87.7% vs 85.8%, CA 11.1% vs 13.1%, AA 1.2% vs 1.1%).1 Ansari et al describe higher frequencies of treatment induced toxicity and higher MTX plasma levels suggesting a higher MTX dose intensity for patients with group 3 MRP4 genotype. They conclude that this might lead to more frequent drug withdrawal or dose reduction, potentially causing higher frequency of relapse within this group.1 MTX dose intensity during early induction consolidation is lower in GMALL protocols (MTX dose 1.5 g/m2 within GMALL protocols2 vs 4 g/m2 within DFCI protocols7,8). Therefore, the proposed modulation of MTX dose intensity by MRP4 genotype may cause other effects than observed within the DFCI protocols. Age difference between analyzed patient series may also influence the prognostic value of specific polymorphisms.