Influence of rhGM-CSF on Ara-C sensitivity of patients with acute myeloid leukemia in relapse: a flow cytometry study.
Twenty-three patients with acute myelogenous leukemia (AML) in first relapse were treated with high-dose cytosine-arabinoside (Ara-C) and amsacrine or idarubicin. To prime the cells, the patients were given rhGM-CSF. We studied the influence of 48-h infusion of rhGM-CSF on proliferation and Ara-C sensitivity of leukemic cells both ex vivo and in vitro. We found that a 48-h infusion of rhGM-CSF increased both white blood cell counts and peripheral blood blast cell percentages. Using a Bromodeoxyuridine/DNA (BrdUrd/DNA) staining in flow cytometry, we found an non-constant increase in cells in the S-phase. Ex vivo 48-h culture of leukemic cells with or without rhGM-CSF, with or without other hematopoietic growth factors (HGFs), showed a greater increase of the cells in the S-phase with GF but no correlation with the ex vivo results. We used a method of quantitation of the DNA synthesis previously described (Lacombe F., et al. (1992) Cytometry 13, 730) to monitor the Ara-C sensitivity of the cells in S-phase before and after 48-h infusion with rhGM-CSF. We observed a great variation in the Ara-C sensitivity of the leukemic cells before and after infusion with rhGM-CSF from one patient to another. The BrdUrd/DNA method seems a convenient method to study the influence of HGFs on Ara-C sensitivity of the patients.
Lacombe
F
F
Laboratoire d'Hématologie, Hôpital Haut-Lévêque CHU, Bordeaux, Pessac, France.
Puntous
M
M
Dumain
P
P
Cony-Makhoul
P
P
Belloc
F
F
Bernard
P
P
Boisseau
M
M
Reiffers
J
J
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000032:analysis; D002453:Cell Cycle; D003561:Cytarabine / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage; D016196:S Phase / Q000187:drug effects
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001973:Bromodeoxyuridine