A cytogenetic and fluorescence in situ hybridization evaluation of interferon-alpha in the treatment of chronic myeloid leukemia.
The effect of interferon-alpha (IFN) for chronic myeloid leukemia (CML) in the chronic phase (CP) was retrospectively evaluated in comparison with that of busulfan (BU) or hydroxyurea (HU) given alone. Among 107 patients diagnosed with CML between 1982 and 1997, 72 CP cases evaluable for long-term follow-up included 13 patients treated with BU alone, 18 with HU alone, and 41 with IFN-based therapy. Complete cytogenetic response (CCR) was achieved in 4/41 IFN cases (10%), and partial or minimal cytogenetic response occurred in 18/41 IFN cases (44%). In contrast, no cytogenetic response (NCR) was achieved in any BU or HU case. IFN treatment for 6 to 60 months was needed to achieve CCR. Overall survival curves revealed that the IFN group had significantly better survival than BU and HU groups (p=0.008 and 0.04, respectively). A significant correlation was found between karyotypic findings and fluorescence in situ hybridization (FISH) analyses in IFN-treated cases (r=0.739, p=0.0001). In some cases, however, the two methods showed discrepancy; BCR/ABL-positive cells represented only 20-75% of interphase bone marrow cells in NCR cases, although all metaphases examined were positive for the Philadelphia chromosome (Ph). A discrepancy was also seen in CCR cases; up to 22% of cells assessed were BCR/ABL-positive. These findings suggest that IFN is a useful therapy for CML in CP, and may have a suppressive effect on the CML clone even in NCR cases. The results also indicate that a combination of FISH and cytogenetic analyses may provide more detailed information for evaluating the efficacy of IFN than conventional cytogenetics alone.
Itoh
T
T
Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Tamura
S
S
Takemoto
Y
Y
Kakishita
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000627:therapeutic use*; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000648:ultrastructure; D010677:Philadelphia Chromosome; D015996:Survival Rate
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl; D006918:Hydroxyurea