In vitro and in vivo effects of rh GM-CSF in acute myeloid leukemia (AML).
70% of patients with newly diagnosed and 50% of patients with relapsed acute myeloid leukemia (AML) can achieve a complete remission with intensive chemotherapy. However, the treatment-associated mortality can be as high as 30% increasing with age, previous chemotherapy and intensity of chemotherapy. GM-CSF was first applied in 36 patients with high risk AML after chemotherapy to reduce the time of critical neutropenia. The early death rate was significantly lower in the GM-CSF group compared to 56 patients of a historic control group with similar risk factors and identical chemotherapy (p less than 0.009). The rate of complete remissions was also significantly higher in the GM-CSF group (p less than 0.09). More recently, GM-CSF was used as a priming agent 24 h prior to start of chemotherapy. 25 patients have entered the study up to now. The cell biological effects of GM-CSF in vivo include an immediate increase of leukemic blasts and of normal myeloid cells in the peripheral blood with a median of 2.0, an increase of cells in the S-phase of the cell cycle in bone marrow biopsies, an increase in DNA polymerase activity, an increase in Ara-C cytotoxicity and immunophenotypic changes compatible with differentiation of leukemic blasts along the pathway of normal myeloid progenitors. GM-CSF has a dual effect on normal and leukemic myeloid cells. It can be safely applied in patients with AML. Prospective randomized trials have to be performed to establish its role in reducing treatment toxicity and in improving the overall treatment results.
Wörmann
B
B
Department of Internal Medicine A, University of Münster, University Hospital, Germany.
Hiddemann
W
W
Frisch
J
J
Zühlsdorf
M
M
Rottmann
R
R
Boeckmann
A
A
Reuter
C
C
Freire
E A
EA
Innig
G
G
Schulz
G
G
D000208:Acute Disease; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D003630:Daunorubicin / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008942:Mitoxantrone / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013866:Thioguanine / Q000008:administration & dosage; D014410:Tumor Stem Cell Assay
D011994:Recombinant Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin