title: Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis.
abstract: OBJECTIVE
  In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myeloreductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential. The aim of this study is to examine changes that occur in the percentage of Ph-negative- and Ph-positive-committed progenitor cells and to determine the relationship between changes and clinical outcome.
  
  
  METHODS
  We followed 15 patients with CML, mobilized and autografted soon after diagnosis with 85%-100% Ph-negative PBPC for a median time of 28 months (range 18-50) after transplant. At 6 months, 1 year, 2 years, and last follow-up, cytogenetic analyses were performed on fresh bone marrow cells and on colony-forming cells (CFC).
  
  
  RESULTS
  Autologous transplantation induces a reduction in the proportion of Ph-positive CFC, from 70%-100% to 0%-25% in the majority of patients (78%). After autografting, 8 of 15 patients achieved a long-lasting cytogenetic remission (median, 24 months; range, 21-43) with a Ph-positivity ranging between 0% and 20% at the level of mature mononuclear cells and colony-forming cells (CFC). In some patients, the majority of CFC remained Ph-negative, whereas the majority of the mature cells were Ph-positive. Other patients (5/15) developed cytogenetic relapse (100% Ph-positive), although they were in hematological remission. We found that detection of Ph-positive long-term-culture initiating cells (LTC-IC) in the marrow at diagnosis was the only factor significantly associated with recurrence of the disease (p < 0.01); on the other hand, the number of Ph-negative LTC-IC infused showed a significant correlation with a better outcome (p < 0.03).
  
  
  CONCLUSIONS
  We have shown that a prolonged period of complete or almost complete Ph-negative hemopoiesis can be achieved in patients with CML who undergo autografting with Ph-negative progenitors. Longer follow-up study will be needed to assess whether these changes are associated with improved survival.
authors.affiliation: Dipartimento di Ematologia Ospedale S. Martino, Genova, Italy. giovannapiaggio@smartino.ge.it
authors.forename: M
authors.initials: M
authors.lastname: Podestà
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: M
authors.initials: M
authors.lastname: Sessarego
authors.forename: A
authors.initials: A
authors.lastname: Pitto
authors.forename: O
authors.initials: O
authors.lastname: Figari
authors.forename: M
authors.initials: M
authors.lastname: Soracco
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.forename: A
authors.initials: A
authors.lastname: Dejana
authors.forename: V
authors.initials: V
authors.lastname: Rosti
authors.forename: G
authors.initials: G
authors.lastname: Fugazza
authors.forename: G
authors.initials: G
authors.lastname: Ravera
authors.forename: E
authors.initials: E
authors.lastname: Lerma
authors.forename: M
authors.initials: M
authors.lastname: Cazzola
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
mesh_terms: D000328:Adult; D005260:Female; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D013997:Time Factors; D014182:Transplantation, Autologous