Impact of exogenous growth factors on proliferation and chemosensitivity of minimal residual acute myeloid leukemia.
The biological heterogeneity of AML makes growth factor augmentation of cell cycle-dependent chemotherapy unlikely to be successful for all patients. Patients whose leukemic cells empirically demonstrate cytokine-induced chemosensitization in vitro might benefit from the concurrent 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, and relapse to determine whether minimal residual leukemia remains growth factor-responsive. Most cases of AML studied at all phases of treatment were growth factor-responsive. Growth factor response of occult remission clonogenic leukemic precursors (CFU-L) was usually concordant with their response at diagnosis. Occult CFU-L were markedly resistant to cytosine arabinoside (median LD99% 20 microM); preincubation with IL-3 or GM-CSF did not significantly improve their ara-C sensitivity. While 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.
Gore
S D
SD
The Johns Hopkins Oncology Center, Baltimore, Maryland, USA. sdgore@welchlink.welch.jhu.edu
Burke
P J
PJ
Weng
L J
LJ
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007377:Interleukin-3 / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000032:analysis / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D018365:Neoplasm, Residual; D012074:Remission Induction; D014410:Tumor Stem Cell Assay
D007377:Interleukin-3; D019394:Ki-67 Antigen; D000677:Amsacrine; D003561:Cytarabine; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003630:Daunorubicin