CLINICAL RELEVANCE OF IN-VITRO DRUG-RESISTANCE TESTING IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - THE STATE-OF-THE-ART

Nowadays about two-thirds of children with acute lymphoblastic leukemi a (ALL) can be cured with chemotherapy, but one-third die from the dis ease. The clinical response of leukemic cells to chemotherapy is rough ly due to two factors: the effective drug levels reaching the cells an d the resistance of these cells to the drugs. The clinical value of ce llular drug resistance in children with ALL is not known. We developed an in vitro assay to study drug resistance in these children. In this article, the main results obtained with this MTT assay on samples fro m 137 children with ALL are summarized: (1) patients whose cells are r esistant to several drugs at initial diagnosis have a poor prognosis; (2) relapsed leukemias show a considerable drug resistance which might partly explain the poor prognosis. Relapsed cases differ in their typ e and degree of resistance; (3) the poor outcome of high risk groups a s defined by age and immunophenotype can partly be explained by specif ic patterns of drug resistance; (4) P-glycoprotein-mediated multidrug resistance is not an important cause of resistance in childhood ALL; a nd (5) no relation exists between the activities of the purine enzymes HGPRT, 5'NT, ADA, and PNP and drug resistance in childhood ALL. The c onclusion is that in vitro drug resistance data have clinical relevanc e and can be used to develop more effective and less toxic treatment s trategies in childhood ALL. (C) 1994 Wiley-Liss, Inc.