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.
Authors: Fouillard Loic , Michallet Mauricette , Van-biezen Anja , Miligan D.W. , Corradini Paolo , Gorin Norbert Claude , Niederwieser Dietger 
Published: October 2019

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.