title: Evaluation of cytogenetic conversion to Ph- haemopoiesis in long-term bone marrow culture for patients with chronic myeloid leukaemia on conventional hydroxyurea therapy, on pulse high-dose hydroxyurea and on interferon-alpha.
abstract: Long-term bone marrow culture (LTBMC) has been used successfully in autologous transplantation in chronic myeloid leukaemia (CML). However, variation between patients in the recovery of Ph- cells in culture limits the application of this procedure to a minority. Treatment that effectively reduces in vivo tumour burden prior to initiation of LTBMC may improve the selection of Ph- cells in culture. To test this hypothesis we evaluated the frequency and degree of cytogenetic conversion to Ph- haemopoiesis in LTBMC from four independent groups of CML patients: Untreated (n = 19); conventional dosage of hydroxyurea (HU) (n = 10); pulse high-dose HU (P-HU) (n = 22) and interferon (IFN)-alpha (n = 12). In this study IFN-alpha therapy resulted in a significantly higher incidence of patients with detectable Ph- clonogenic cells in the marrow (P = 0.01) and with > or = 50% Ph- haemopoiesis in LTBMC as compared to newly diagnosed patients (P = 0.05). Also, sequential culture studies undertaken in 14 CML patients at diagnosis and following the start of pulse highdose HU therapy showed that in eight patients the average proportion of Ph- metaphases detected in LTBMC substantially increased from 1.7% (range 0-7) at diagnosis to levels of 71% (range 14-100) after treatment. Therefore we conclude that the use of IFN or pulse high-dose HU in early stage disease appears to create an opportunity to harvest the marrow for long-term culture (LTC) purging with reduced leukaaemic burden.
authors.affiliation: CRC Department of Experimental Haematology, Christie Hospital NHS Trust, Manchester.
authors.forename: L H
authors.initials: LH
authors.lastname: Coutinho
authors.forename: M L
authors.initials: ML
authors.lastname: Brereton
authors.forename: A M
authors.initials: AM
authors.lastname: Santos
authors.forename: W D
authors.initials: WD
authors.lastname: Ryder
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: J A
authors.initials: JA
authors.lastname: Yin
authors.forename: T M
authors.initials: TM
authors.lastname: Dexter
authors.forename: N G
authors.initials: NG
authors.lastname: Testa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D016898:Interferon-alpha / Q000008:administration & dosage*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
chemical_list: D016898:Interferon-alpha; D006918:Hydroxyurea