title: Autologous transplantation with Philadelphia-negative progenitor cells for patients with chronic myeloid leukaemia (CML) failing to attain a cytogenetic response to alpha interferon.
abstract: Between October 1993 and March 1999, 29 patients with CML who were ineligible for allogeneic BMT underwent PBSC harvest using idarubicin, cytarabine and G-CSF. In 9/29 (31%) patients all collected stem cells were Ph-negative, and 15/29 patients' (52%) collections were substantially (>95%) Ph-negative. The proportion of patients from whom Ph-negative stem cells were obtained was similar between patients who had, or had not, received prior alphaIFN. Fifteen patients in chronic phase (median age 45) proceeded to PBSCT following busulphan 16 mg/m2 and cyclophosphamide 120 mg/m2. Nine of the 13 patients who had failed to respond to prior alphaIFN proceeded to stem cell transplantation as soon as was feasible and six of the newly diagnosed patients were transplanted after failing to achieve a cytogenetic response after a minimum of 12 months on alphaIFN following progenitor cell harvest. The median number of days to neutrophils >0.5 and platelet >50 was 18 (range 13-69) and 28 (range 13-234), respectively. There was no procedure-related mortality. At median follow-up of 2.3 years post autograft 10 of 15 patients remain alive and in chronic phase. Overall survival for all 27 patients at 5 years after initial diagnosis is 70% and median survival from diagnosis 7.3 years. Survival for alphaIFN non-responders who were transplanted is 74% at 5 years from diagnosis and 75% at 3 years from transplant. Cytogenetic analysis performed 3 months post transplant demonstrated one patient with a complete cytogenetic response, seven with a partial response and three with no response. Six patients remain partially Ph-negative, with one major CR. Survival for all patients in the protocol is favourable compared with conventional therapy and is particularly encouraging following PBSCT for alphaIFN non-responsive patients. Patients not responding to alphaIFN can be induced into Ph-negativity with PBSCT but this may not always be sustainable. There seems to be no obvious disadvantage in harvesting stem cells after prior exposure to alphaIFN, providing an adequate alphaIFN-free rest period is used.
authors.affiliation: Department of Haematology, St Bartholomew's and Royal London Hospital School of Medicine and Dentistry, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: McBride
authors.forename: J D
authors.initials: JD
authors.lastname: Cavenagh
authors.forename: A C
authors.initials: AC
authors.lastname: Newland
authors.forename: D M
authors.initials: DM
authors.lastname: Lillington
authors.forename: C
authors.initials: C
authors.lastname: Murrell
authors.forename: S M
authors.initials: SM
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D016898:Interferon-alpha / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D002066:Busulfan; D015255:Idarubicin