Clinical significance of P-glycoprotein (P-gp) expression in childhood acute lymphoblastic leukemia. Results of a 6-year prospective study.

Abstract

P-glycoprotein (P-gp), a cellular drug-efflux pump is thought to be one of the major causes of multidrug resistance in malignancies. Since therapeutic strategies are being developed to circumvent drug resistance by inhibiting P-gp, prospective studies concerning the clinical relevance of P-gp in childhood leukemia are warranted. P-gp was studied in 102 consecutive cases of de novo childhood ALL and in 34 relapsed patients. An immunocytochemical technique with two monoclonal antibodies (C219,4E3) was used on bone marrow and blood smears. 12/34 (35%) children were scored positive at relapse compared to 12/102 (12%) children with newly diagnosed ALL (p = 0.006). No correlation between P-gp expression and clinical and hematological parameters was seen. All patients were treated according to the EORTC-CLCG protocols (survival at 5 years = 85%). 20/102 patients relapsed. The mortality rate in the P-gp positive group was significantly worse (Logrank P = 0.009) than in the P-gp negative patients. In the relapsed patient population 10/12 P-gp positive cases experienced an unfavourable outcome compared with 10/22 P-gp negative patients [Risk Ratio 2.21 (0.90-5.45)]. P-glycoprotein expression in newly diagnosed childhood ALL is an independent prognostic parameter for dismal outcome. P-gp positivity at relapse tends towards an adverse clinical outcome compared to the P-gp negative relapsed population.