title: Clonogenic assay is not predictive but reflects therapeutic efficacy of interferons in the treatment of chronic myelogenous leukemia.
abstract: Patients with chronic myelogenous leukemia (CML) have been treated with interferon (IFN) alpha-2b alone or in combination with IFN gamma. In order to predict clinical response to IFN, bone marrow samples from 15 CML patients were incubated with serial dilutions of IFN alpha-2b to obtain the IC50 values for erythroid burst forming units (BFU-E) and granulocyte-macrophage colony forming units (CFU-GM). A dose-dependent inhibition of at least one lineage was observed in all but one sample. An inhibitory effect of greater than 50% was reached for BFU-E in 8/14 patients and for CFU-GM in 10/14 patients. All three patients with no response (NR) to IFN treatment had IFN-sensitive BFU-E and CFU-GM. In four patients with hematologic remission (HR) or partial hematologic remission (PHR), BFU-E or CFU-GM were affected very little by the inhibitory effect of IFN. These observations suggest no predictive value for pretesting IFN sensitivity in vitro. The in vivo effect of IFN on the hemopoietic progenitor cells BFU-E and CFU-GM was evaluated in patients treated with either IFN alpha-2b alone (n = 11), or in combination with low dose IFN gamma (n = 10). All patients were newly diagnosed and not pretreated. After a median treatment duration of 11 months (range 3-25) a significant decrease in BFU-E and CFU-GM was observed in both groups of patients. We conclude that in vitro colony growth reflects the therapeutic efficacy of IFN.
authors.affiliation: Department of Internal Medicine (Cancer Research), West German Cancer Center Essen, University of Essen Medical School.
authors.forename: U B
authors.initials: UB
authors.lastname: Wandl
authors.forename: N
authors.initials: N
authors.lastname: Niederle
authors.forename: M
authors.initials: M
authors.lastname: Kranzhoff
authors.forename: S
authors.initials: S
authors.lastname: Seeber
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007371:Interferon-gamma