CORTICOSTEROID RESISTANCE IS INCREASED IN LYMPHOBLASTS FROM ADULTS COMPARED WITH CHILDREN - PRELIMINARY-RESULTS OF IN-VITRO DRUG-SENSITIVITY STUDY IN ADULTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

The prognosis of acute lymphoblastic leukaemia (ALL) in adults is poor compared with children in terms of complete remission (CR) and leukae mia-free survival. In children in vitro resistance of leukaemic cells to various cytotoxic agents is an independent poor prognostic marker, but the relevance of in vitro drug resistance in adults to poor progno sis has not been described. Lymphoblasts from 16 adults and 32 childre n with ALL at initial presentation were assayed for in vitro drug sens itivity in a short-term culture system using the reduction of 3-(4,5-d imethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indi cator of cell viability. The following drugs were tested: prednisolone , daunorubicin, mitozantrone, etoposide, melphalan and 6-thioguanine, At initial presentation, lymphoblasts from adults demonstrated a signi ficantly higher degree of in vitro resistance to prednisolone than tho se from children (P < 0.01). Glucocorticoid resistance may be a fundam ental difference between adult and childhood ALL which may underlie di fferent biological aspects and also explain the difference in prognosi s. Lymphoblasts from adults who achieved CR were more sensitive in vit ro to prednisolone, (P = 0.07), daunorubicin (P < 0.05), mitozantrone (P < 0.01) and melphalan (P < 0.05) than cells from those who did not. The MTT assay can predict response to induction chemotherapy in adult s and therefore discriminate between standard- and high-risk patients. The assay, however, is not suitable for selection of the most effecti ve agent for treatment because of in vitro cross-resistance of lymphob lasts to various drugs tested.