title: Filgrastim-induced stem cell mobilization in chronic myeloid leukaemia patients during imatinib therapy: safety, feasibility and evidence for an efficient in vivo purging.
abstract: Therapy with imatinib mesylate is limited by cellular resistance in chronic myeloid leukaemia (CML). Further, the limited availability of matching stem cell donors or an unfavourable risk profile for allogeneic stem cell transplantation (SCT) reduces the number of therapeutic options in a number of patients. To assess the possibility of stem cell mobilization (SCM) during imatinib therapy we performed granulocyte colony-stimulating factor (filgrastim)-induced SCM and subsequent aphaeresis in 15 chronic phase and three accelerated phase CML patients. Aphaeresis was successful in 13 patients (72%) (> or =2.0 x 10(6) CD34+ cells/kg body weight) and five (28%) harvests could be obtained, which were negative for BCR/ABL mRNA as assessed by nested-reverse transcription polymerase chain reaction (RT-PCR). All harvests, except one, were negative after first round RT-PCR, implicating a low level of CML cell contamination. There was no significant change in peripheral BCR/ABL transcript load after SCM as assessed by quantitative real-time RT-PCR. Fifteen patients remained stable in complete cytogenetic remission (CCR) during a median observation period of 9.3 months. One patient achieved a molecular remission shortly after SCM. Another patient who exhibited rising BCR/ABL mRNA levels before SCM achieved CCR after autologous SCT with the generated harvest. One patient with a Philadelphia chromosome-negative, BCR/ABL-positive CML showed a cytogenetic relapse 6 months after SCM. We conclude that filgrastim-induced CD34+ cell aphaeresis under simultaneous imatinib medication is safe and feasible in CML patients. Additionally, we found evidence that this procedure could generate stem cell harvests that exhibit non-detectable levels of BCR/ABL mRNA.
authors.affiliation: Medizinische Klinik m.S. Hämatologie und Onkologie, Campus Virchow-Klinikum, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. karl-anton.kreuzer@charite.de
authors.forename: Karl-Anton
authors.initials: KA
authors.lastname: Kreuzer
authors.forename: Christine
authors.initials: C
authors.lastname: Klühs
authors.forename: Gökben
authors.initials: G
authors.lastname: Baskaynak
authors.forename: Kamran
authors.initials: K
authors.lastname: Movassaghi
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D000069585:Filgrastim; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069585:Filgrastim