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...

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Bibliographic Details
Published in:Leukemia & lymphoma 1998, Vol.29 (3-4), p.339-350
Main Authors: Gore, Steven D., Burke, Philip J., Weng, Li-Jun
Format: Article
Language:English
Subjects:
Acute Disease
acute myeloid leukemia
Adult
Aged
Amsacrine - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
cell cycle growth factors
CFU-L
chemosensitivity
Cytarabine - administration & dosage
cytosine arabinoside
Daunorubicin - administration & dosage
drug resistance
Etoposide - administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
Humans
Interleukin-3 - therapeutic use
Ki-67 Antigen - analysis
Ki-67 Antigen - drug effects
Ki67
Leukemia, Myeloid - drug therapy
Leukemia, Myeloid - pathology
Middle Aged
minimal residual disease
Neoplasm, Residual
Remission Induction
Tumor Stem Cell Assay
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Summary: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 μM); 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.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428199809068570