IMPACT OF EXOGENOUS GROWTH-FACTORS ON PROLIFERATION AND CHEMOSENSITIVITY OF MINIMAL RESIDUAL ACUTE MYELOID-LEUKEMIA

The biological heterogeneity of AML makes growth factor augmentation o f cell cycle-dependent chemotherapy unlikely to be successful for all patients. Patients whose leukemic cells empirically demonstrate cytoki ne-induced chemosensitization in vitro might benefit from the concurre nt administration of growth factors during consolidation chemotherapy. We have explored the growth factor-dependence and response of primary bone marrow samples from patients with AML at diagnosis, remission, a nd relapse to determine whether minimal residual leukemia remains grow th factor-responsive. Most cases of AML studied at all phases of treat ment were growth factor-responsive. Growth factor response of occult r emission clonogenic leukemic precursors (CFU-L) was usually concordant with their response at diagnosis. Occult CFU-L were markedly resistan t to cytosine arabinoside (median LD99% 20 mu M); preincubation with I L-3 or GM-CSF did not significantly improve their ara-C sensitivity. W hile occult remission CFU-L appear to remain,growth factor-responsive, it appears unlikely that growth factor augmentation of consolidation chemotherapy will overcome the important problem of drug resistance of residual leukemia.