P‐glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6‐year prospective study

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Abstract
P‐glycoprotein (P‐gp), a cellular drug‐efflux pump, is thought to be one of the major causes of multidrug resistance (MDR) in malignancies. Since therapeutic strategies are being developed to circumvent drug resistance by inhibiting P‐gp function, large prospective studies evaluating the clinical relevance of P‐gp in childhood acute lymphoblastic leukaemia (ALL) are warranted. P‐gp expression was evaluated over a period of 6 years in 102 consecutive patients with de novo childhood ALL and in 35 children with relapse of ALL. Bone marrow and blood smears were studied immunocytochemically with two monoclonal antibodies at initial diagnosis and at relapse. P‐gp expression was found in 14 (14%) patients at initial diagnosis. After induction treatment, complete remission was achieved in 100/102 patients (98%), of whom 19 relapsed. Cumulative event‐free survival was significantly higher in the P‐gp‐negative group compared with the P‐gp‐positive population (Logrank P = 0.02). Multivariate analysis showed the results to be independent of age, WBC count and karyotype, and concomitantly underlined the importance of MDR1 phenotype detection in childhood ALL. P‐gp expression was more frequently found at relapse (34%) than at primary diagnosis (P = 0.01). In the relapsed patient group, P‐gp‐positive patients had a 2‐fold greater risk for adverse clinical outcome than the P‐gp‐negative relapsed patients. P‐gp expression was not induced by exposure to previous chemotherapy since the majority of P‐gp‐negative patients remained negative at relapse. P‐glycoprotein expression in newly diagnosed childhood ALL is an independent adverse prognostic parameter with a predictive value for relapse.