title: Mobilization of Philadelphia-negative peripheral blood progenitor cells with chemotherapy and rhuG-CSF in chronic myelogenous leukaemia patients with a poor response to interferon-alpha.
abstract: The purpose of this cooperative study was to evaluate the quantity and quality of Ph1-negative progenitor cells mobilized in the peripheral blood of patients with chronic myelogenous leukaemia soon after aplasia induced by chemotherapy. 32 patients ineligible for allografting who were cytogenetically refractory to interferon-alpha (IFN-alpha) were entered into this study. The chronic phase varied widely, with a median duration of 17 months (range 3-90 months). All patients were treated with intensive conventional chemotherapy regimens and recombinant human granulocyte colony-stimulating factor (rhuG-CSF, lenograstim). Peripheral blood progenitor cells (PBPC) were harvested by leukaphereses during early recovery from chemotherapy-induced aplasia. A total of 119 leukaphereses were performed. Median numbers of CD34+ cells and CFU-GM collected were 2.04 x 10(6)/kg and 2 9 x 10(4)/kg, respectively. There was a significant correlation between white cell count and number of CD34+ cells in the leukaphereses (P = 0.0001, r2 = 0.41, n = 104). A strict correlation between the number of CD34+ cells and CFU-GM in the leukapheretic product (P = 0.0001, r2 = 0.39, n = 110) was observed. 21% of evaluable patients (6/29) achieved a complete cytogenetic remission in the leukapheretic product and the other four patients achieved a major cytogenetic response for an overall response of 35% (10/22 patients). To date, 16 patients have been autografted and are alive. Five of them are Ph1-negative (three patients) or partially Ph1-negative (two patients). In conclusion, despite the high-risk characteristics of this study population, Ph1-negative PBPC were successfully mobilized in more than one-quarter of patients using a chemotherapy plus rhuG-CSF regimen. The importance of this achievement is increased by the current lack of other practical methods of rescuing Ph-negative cells in such patients.
authors.affiliation: Haematology/Autografting Unit Azienda Ospedaliera e Cliniche Universitarie Convenzionate, Ospedale San Martino, Genova, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Carella
authors.forename: B
authors.initials: B
authors.lastname: Simonsson
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: A
authors.initials: A
authors.lastname: Lennard
authors.forename: M
authors.initials: M
authors.lastname: Boogaerts
authors.forename: N C
authors.initials: NC
authors.lastname: Gorin
authors.forename: J F
authors.initials: JF
authors.lastname: Tomas-Martinez
authors.forename: F
authors.initials: F
authors.lastname: Dabouz-Harrouche
authors.forename: L
authors.initials: L
authors.lastname: Gautier
authors.forename: N
authors.initials: N
authors.lastname: Badri
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D016898:Interferon-alpha / Q000627:therapeutic use*; D000078224:Lenograstim; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D000078224:Lenograstim; D003520:Cyclophosphamide; D002066:Busulfan; D015255:Idarubicin; D003630:Daunorubicin