title: The detection of Philadelphia chromosome negative metaphases in long-term bone marrow cultures of the peripheral blood from patients with chronic myeloid leukemia predicts response to interferon-alpha 2a.
abstract: The cytogenetic response of 10 patients with chronic myeloid leukaemia (CML) to human recombinant interferon-alpha 2a (rhIFN alpha 2a) was compared to the Philadelphia chromosome (Ph) status of the pre-treatment peripheral blood cells after in vitro culture under long-term bone marrow culture (LTBMC) conditions. Pre-treatment light density peripheral blood cells were cultured in LTBMC on sex-mismatched irradiated allogeneic stromal layers with weekly cytogenic examination of metaphases in the non-adherent cell fraction. This was correlated with the patients' response to rhIFN alpha. Two groups of patients, five showing a cytogenetic response (responsive) and five who failed to achieve a cytogenetic response (nonresponsive) were studied. At the initiation of the LTBMCs the Ph' was found to be present in 100% of the cells analysed for nine patients and 97% for one patient. Pretreatment peripheral blood from four responsive patients demonstrated a decline in the proportion of Ph'-positive cells (Ph+) after 1 to 2 weeks in LTBMC. In contrast, peripheral blood from all the non-responsive subjects showed persistence of the Ph+ clone in 100% of the cells analysed out to a maximum of 3 to 5 weeks in LTBMC. A significant difference was observed (Fisher exact test, p = 0.023) between the two patient groups in respect to the appearance of normal clones in the nonadherent population. The presence of Ph- metaphases in LTBMC of peripheral blood cells of CML patients may predict their cytogenetic response to rhIFN alpha 2a.
authors.affiliation: Leukaemia Research Unit, Hanson Centre for Cancer Research, Adelaide, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Gronthos
authors.forename: L B
authors.initials: LB
authors.lastname: To
authors.forename: S
authors.initials: S
authors.lastname: Moore
authors.forename: J M
authors.initials: JM
authors.lastname: Suttle
authors.forename: C A
authors.initials: CA
authors.lastname: Juttner
mesh_terms: D001853:Bone Marrow / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008677:Metaphase; D011379:Prognosis; D011994:Recombinant Proteins; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; D007371:Interferon-gamma