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)-α (n = 12). In this study IFN-α therapy resulted in a significantly higher incidence of patients with detectable Ph− clonogenic cells in the marrow (P = 0.01) and with ≥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 high-dose 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 leukaemic burden.
