Dose intensification and molecular responses in patients with chronic lymphocytic leukaemia: a phase II single centre study

Abstract

Chronic lymphocytic leukaemia is a condition which has a median age of 65 years but approximately 10% of patients are younger than 50. Fludarabine has been shown to produce better response rates than conventional single agent or combination chemotherapy but as yet no improved survival. We have treated a series of 10 patients presenting with de novo (six) or relapsed (four) chronic lymphocytic leukaemia (CLL) with fludarabine as cytoreduction treatment and consolidation of the response with CD34 selected peripheral blood stem cell transplantation using cyclophosphamide and total body irradiation (TBI) as conditioning therapy. We report here on the progenitor cell harvest characteristics and clinical and molecular responses to both fludarabine and high-dose consolidation. Our results indicate that at 3 months post transplant clinical remissions were induced in 10/10 patients and molecular responses in 7/8 (88%) evaluable patients. Molecular relapses occurred on long-term follow-up at 6, 9, 12 and 24 months post transplant but patients continued in clinical and haematological remission. Two patients have died from progressive disease and a third patient from aggressive high grade lymphoma. Median survival from the time of transplantation for the group overall was 22 months (range 6–45). There was no procedure-related mortality in the first 100 days.