Autologous transplantation with Philadelphia-negative progenitor cells forpatients with chronic myeloid leukaemia (CML) failing to attain a cytogenetic response to alpha interferon

Between October 1993 and March 1999, 29 patients with CML who were ineligib le for allogeneic BMT underwent PBSC harvest using idarubicin, cytarabine a nd G-CSF. In 9/29 (31%) patients all collected stem cells were Ph-negative, and 15/29 patients' (52%) collections were substantially (>95%) Ph-negativ e. The proportion of patients from whom Ph-negative stem cells were obtaine d was similar between patients who had, or had not, received prior alpha IF N. Fifteen patients in chronic phase (median age 45) proceeded to PBSCT fol lowing busulphan 16 mg/m(2) and cyclophosphamide 120 mg/m(2). Nine of the 1 3 patients who had failed to respond to prior alpha IFN proceeded to stem c ell 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 alpha IFN following progenitor cell harvest . The median number of days to neutrophils >0.5 and platelet >50 was 18 (ra nge 13-69) and 28 (range 13-234), respectively. There was no procedure-rela ted mortality. At median follow-up of 2.3 years post autograft 10 of 15 pat ients remain alive and in chronic phase. Overall survival for all 27 patien ts at 5 years after initial diagnosis is 70% and median survival from diagn osis 7.3 years. Survival for alpha IFN non-responders who were transplanted is 74% at 5 years from diagnosis and 75% at 3 years from transplant. Cytog enetic analysis performed 3 months post transplant demonstrated one patient with a complete cytogenetic response, seven with a partial response and th ree with no response. Six patients remain partially Ph-negative, with one m ajor CR. Survival for all patients in the protocol is favourable compared w ith conventional therapy and is particularly encouraging following PBSCT fo r alpha IFN non-responsive patients. Patients not responding to alpha IFN c an be induced into Ph-negativity with PBSCT but this may not always be sust ainable. There seems to be no obvious disadvantage in harvesting stem cells after prior exposure to alpha IFN, providing an adequate alpha IFN-free re st period is used.