EVALUATION OF CYTOGENETIC CONVERSION TO PH(-) HEMATOPOIESIS IN LONG-TERM BONE-MARROW CULTURE FOR PATIENTS WITH CHRONIC MYELOID-LEUKEMIA ON CONVENTIONAL HYDROXYUREA THERAPY, ON PULSE HIGH-DOSE HYDROXYUREA AND ON INTERFERON-ALPHA

Long-term bone marrow culture (LTBMC) has been used successfully in au tologous transplantation in chronic myeloid leukaemia (CML). However, variation between patients in the recovery of Ph(-) cells in culture l imits 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 hyp othesis we evaluated the frequency and degree of cytogenetic conversio n to Ph(-) haemopoiesis in LTBMC from four independent groups of CML p atients: 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 i n the marrow (P = 0.01) and with greater than or equal to 50% Ph(-) ha emopoiesis in LTBMC as compared to newly diagnosed patients (P = 0.05) . Also, sequential culture studies undertaken in 14 CML patients at di agnosis and following the start of pulse high-dose HU therapy showed t hat in eight patients the average proportion of Ph(-) metaphases detec ted in LTBMC substantially increased from 1.7% (range 0-7) at diagnosi s to levels of 71% (range 14-100) after treatment. Therefore we conclu de that the use of IFN or pulse high-dose HU in early stage disease ap pears to create an opportunity to harvest the marrow for long-term cul ture (LTC) purging with reduced leukaemic burden.