title: Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase.
abstract: The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
authors.affiliation: Department of Internal Medicine, University Hospital, SE-751 85 Uppsala, Sweden. ulla.olsson.stromberg@akademiska.se
authors.forename: Ulla
authors.initials: U
authors.lastname: Olsson-Strömberg
authors.forename: Martin
authors.initials: M
authors.lastname: Höglund
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Inger
authors.initials: I
authors.lastname: Braide
authors.forename: Karin
authors.initials: K
authors.lastname: Carlson
authors.forename: Gösta
authors.initials: G
authors.lastname: Gahrton
authors.forename: Gunnar
authors.initials: G
authors.lastname: Grimfors
authors.forename: Robert
authors.initials: R
authors.lastname: Hast
authors.forename: Rickard
authors.initials: R
authors.lastname: Lerner
authors.forename: Olle
authors.initials: O
authors.lastname: Linder
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Eva
authors.initials: E
authors.lastname: Löfvenberg
authors.forename: Claes
authors.initials: C
authors.lastname: Malm
authors.forename: Per-Gunnar
authors.initials: PG
authors.lastname: Nilsson
authors.forename: Christer
authors.initials: C
authors.lastname: Paul
authors.forename: Stig
authors.initials: S
authors.lastname: Rödjer
authors.forename: Leif
authors.initials: L
authors.lastname: Stenke
authors.forename: Ulf
authors.initials: U
authors.lastname: Tidefeldt
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Uden
authors.forename: Anders
authors.initials: A
authors.lastname: Wahlin
authors.forename: Lars
authors.initials: L
authors.lastname: Vilen
authors.forename: Ingemar
authors.initials: I
authors.lastname: Winqvist
authors.forename: Olle
authors.initials: O
authors.lastname: Zettervall
authors.forename: Gunnar
authors.initials: G
authors.lastname: Oberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D007371:Interferon-gamma / Q000008:administration & dosage; D000078224:Lenograstim; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D016879:Salvage Therapy; D014182:Transplantation, Autologous
chemical_list: D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D007371:Interferon-gamma; D006918:Hydroxyurea