In Vitro Purging in Autologous Stem Cell Transplantation for Chronic Lymphocytic Leukaemia. A Retrospective Analysis on Behalf of the Chronic Leukaemia Working Party of the EBMT.
Abstract High dose therapy (HDT) and autologous stem cell transplantation (ASCT) is part of the therapeutic strategy in a subset of patients with chronic lymphocytic leukaemia (CLL). There are no data evaluating in vitro purging in CLL. We started a retrospective study comparing CLL receiving HDT and ASCT with either unpurged or purged autograft. Adult patients >16 year old (y.o), with B CLL, autografted with peripheral blood, from 1992 to 2002 were selected. Enough data in the EBMT registry were available for 210 patients . Autograft was unpurged in 130 patients, and purged in 80 patients. Purging consisted of CD34 positive selection in 62 patients, CD34 positive and CD19 negative selection in 11 patients, a negative selection alone in 4 patients, the technique was unknown in 3 patients. Comparison of distribution for unpurged versus purged ASCT showed a sex ratio male/female of 5.1 and 2.5 (p=0.03) respectively, a median age of 52 yo and 50 yo (p=0.57) respectively, a Binet stage at diagnosis of 27% and 30% for stage A, 44% and 50% for stage B, 29% and 20% for stage C (p=0.55) respectively. The majority of patients received a combination of G-CSF and chemotherapy for stem cell mobilisation (86% and 84% respectively), the median time from diagnosis to mobilisation was longer for unpurged (30 months) than for purged ASCT (18 months) (p=0.016). Comparison of characteristics at transplants showed no difference for the status at transplant: 33% of patients with unpurged ASCT were in complete remission (CR) and 33% with purged ASCT; 61% and 57% were in partial remission (PR) respectively, 6% and 10% were in stable/progressive disease respectively (p=0.56). HDT comprised total body irradiation for 30% of unpurged and 72.5% for purged ASCT (p<0.0001). The median dose of CD34 positive cells infused was 3.2x106/kg and 2.6x106/kg respectively. The majority of patients engrafted: 98.5% and 96.3% respectively. There was no difference for neutrophil recovery (11 days and 12 days respectively) and platelet recovery (17 days and 20 days respectively). Comparison of outcome at 3 years for unpurged and purged ASCT showed a leukaemia free survival (LFS) of 40% and 55% (p=0.10) respectively, a relapse incidence (RI) of 52% and 37% (p=0.07) respectively, a non relapse mortality (NRM) of 8% and 8% respectively. According to the status at transplant LFS was identical for patients in CR: 55% and 57% for unpurged and purged respectively. For patients in PR, LFS was 25% and 58% (p=0.03) respectively and RI 60% and 30% respectively. For patients in stable/progressive disease LFS was 40% and 55% (p=0.10) and RI 52% and 37% (p=0.07) respectively. By multivariate analysis a trend for a lower RI was associated to in vitro purging (p=0.08, HR:0.63). Study of interactions between purging and prognostic factors showed that purging and PR status at time of ASCT was associated to a lower RI (p=0.06, HR:0.32). These results indicates that there might be a benefit of in vitro purging in some patients with B CLL according to their status at transplant.