title: Interferon-alpha protects Philadelphia-negative progenitors from exhaustion in chronic myeloid leukemia patients with cytogenetic response.
abstract: BACKGROUND
  Normal immature hematopoietic progenitors are relatively well preserved in most patients newly diagnosed with chronic myeloid leukemia, but tend to decline rapidly with time. Such exhaustion could reflect a suppressive effect of the Philadelphia positive clone expansion and/or be induced by Interferon-alpha treatment.
  
  
  METHODS
  A total of 51 CML patients were classified into three groups. Newly diagnosed untreated patients were group A (n=30). Of the 21 treated individuals with Interferon-alpha, for at least 12 months, 15 showed no cytogenetic response (group B) while six showed persisting major/complete response (group C). Patients belonging to groups A and B were mobilized with chemotherapy plus G-CSF while patients of group C received a short course of G-CSF only.
  
  
  RESULTS
  Patients responding to IFN-alpha (group C) showed comparable numbers of bone marrow Ph- long-term culture initiating cells to those of newly diagnosed individuals (group A): 8.5 (<1-65)/10(6) MNC vs 10.5 (<1-30), while non-responders had markedly lower numbers: <1 (<1-5). The amount of Ph- LTC-IC collected was significantly lower in patients of group B 1.8 (0-325)x10(2)/kg than in patients of either group A 31.3 (0-952)x10(2)/kg (P<0.002) or group C 109 (8-259)x10(2)/kg (P<0.01). Interestingly, five patients of group B who had 100% Ph+ metaphases, but Ph- progenitors in their bone marrow, mobilized normal amounts of Ph(-) progenitors.
  
  
  CONCLUSIONS
  These findings suggest that the decline of normal hematopoietic progenitors, currently observed in the majority of CML patients, is not induced by IFN-alpha treatment, but it is likely due to the expanding leukemic clone. They also indicate that normal hematopoietic reservoir is consistently preserved in patients given IFN-alpha early after diagnosis and achieving a stable cytogenetic response.
authors.affiliation: Divisione Ematologia II, Ospedale San Martino, Genova, Italy. frafrassoni@smartino.ge.it
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
authors.forename: M
authors.initials: M
authors.lastname: Podestà
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: V
authors.initials: V
authors.lastname: Rosti
authors.forename: A
authors.initials: A
authors.lastname: Pitto
authors.forename: M
authors.initials: M
authors.lastname: Soracco
authors.forename: O
authors.initials: O
authors.lastname: Figari
authors.forename: F
authors.initials: F
authors.lastname: Vassallo
authors.forename: G
authors.initials: G
authors.lastname: Fugazza
authors.forename: G
authors.initials: G
authors.lastname: Bergamaschi
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: M
authors.initials: M
authors.lastname: Sessarego
authors.forename: M
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects; D016022:Case-Control Studies; D002452:Cell Count; D020732:Cytogenetic Analysis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D010677:Philadelphia Chromosome; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D016898:Interferon-alpha; D016179:Granulocyte Colony-Stimulating Factor