RELATION BETWEEN AGE, IMMUNOPHENOTYPE AND IN-VITRO DRUG-RESISTANCE IN395 CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA - IMPLICATIONS FOR TREATMENT OF INFANTS

The prognosis of infant ALL, characterized by a high incidence of the immature CD10 negative B-lineage ALL (proB ALL) is poor. This study ai med to determine the resistance profile of infant ALL cells. In vitro drug resistance was determined by the MTT assay of 395 children with A LL at initial diagnosis: there were 21 infants <1.5 years of which nin e <1 year, 284 children aged 1.5-10 years (intermediate age group) and 90 children >10 years. Immunophenotyping resulted in 310 cALL/preB AL L, 69 T-ALL, 15 proB ALL and one unknown cases. The following drugs we re tested: daunorubicin, doxorubicin, mitoxantrone, idarubicin (Ida), prednisolone (Pred), dexamethasone (DXM), vincristine (VCR), Asparagin ase (Asp), 6-MP, 6-TG, AraC, VM26 and 4-HOO-ifosfamide (Ifos). Infants <1.5 years were significantly more resistant to Pred (>500-fold), Asp (11-fold) and VM26 (2.7-fold) but significantly more sensitive to Ara C (2.3-fold) compared to the intermediate age group. When analyzing in fants <1 year of age similar results were found. ProB ALL cells (seven infants <1.5 years; eight children >1.5 years) were significantly mor e resistant to glucocorticoids, Asp, thiopurines, anthracyclines and I fos compared to cALL/preB ALL but more sensitive to Ara-C. Cells from children >10 years were significantly more resistant to Pred, DXM, Asp , Ida and 6-MP. T-ALL cells showed a strong resistance to Pred, Asp an d VCR and a mild but significant resistance to all other drugs except thiopurines and VM26. We conclude that the poor prognosis of infant AL L is associated with a resistance to glucocorticoids and Asp. However, ALL cells from infants show a relatively high sensitivity to Ara-C wh ich suggests that infants with ALL might benefit from treatment schedu les that incorporate more Ara-C than the current treatment protocols.