Risk‐stratified adoptive cellular therapy following allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukaemia

Abstract

SummaryFollowing reduced intensity-conditioned allogeneic stem cell transplantation (RIC allo-SCT) for chronic lymphocytic leukaemia (CLL), there is an inverse relationship between relapse and extensive chronic graft-versus-host disease (GVHD). We evaluated outcomes in 50 consecutive patients with CLL using the approach of alemtuzumab-based RIC allo-SCT and preemptive donor lymphocyte infusions (DLI) for mixed chimerism or minimal residual disease (MRD), with the intention of reducing the risk of GVHD. Forty two patients had high-risk disease, including 30% with 17p deletion (17pÀ). Of patients who were not in complete remission (CR) entering transplant, 83% subsequently achieved MRD-negative CR. Both MRD detection and uncorrected mixed chimerism were associated with greater risks of treatment failure. Nine of sixteen patients receiving DLI for persistent or relapsed disease subsequently attained MRD-negative CR. With a median follow-up of 4Á3 years, 4-year current progression-free survival was 65% and overall survival was 75% (60% and 61% in respectively, patients with 17pÀ). DLI was associated with a 29% cumulative incidence of severe GVHD and mortality of 6Á4%. At last follow-up, 83% of patients in CR were off all immunosuppressive treatment. In conclusion, the directed delivery of allogeneic cellular therapy has the potential to induce durable remissions in high-risk CLL without incurring excessive GVHD.

Transplantation in CLL: what we can learn from a dinosaur

“…To this end, it is noteworthy that only 67% of all patients enrolled in the HOVON trial made it to transplant. Accordingly, the 2-year PFS rate by ITT was about one-third lower than the corresponding PFS time measured from HSCT: whereas the 61% 2-year PFS of the patients actually allotransplanted in this study is at least comparable to that of the other larger series, [4][5][6][7][8][9] the 2-year PFS by ITT decreases to 42%. This figure is still markedly superior to former CIT salvage 2-year PFS figures in high-risk CLL, which per definition are close to zero 2,10 but not obviously better than those that can be achieved for instance with ibrutinib, even in high-risk R/R CLL.…”

Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation

“…A few treatment options for salvage therapy after alloSCT have shown moderate efficacy, including monoclonal anti-CD20 antibodies, donor lymphocyte infusions, lenalidomide and standard chemotherapy. [16][17][18][19][20] Here, we report on the use of ibrutinib as treatment for relapsed CLL patients following alloSCT. In three out of five of our patients, ibrutinib was started after multiple lines of other treatment regimens following post-alloSCT relapse had failed.…”

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

“…[1][2][3][4][5][6] The drawbacks of this procedure are NPM and cGvHD-related morbidity, justifying alloSCT only for very high-risk CLL patients. 17 Our report is the first that prospectively describes outcome of patients that fulfill one or more of the EBMT Transplant Consensus criteria, have a treatment indication and entered the study at the start of remission induction with the aim to proceed to alloSCT.…”

“…[1][2][3][4][5][6] Evidence for a GvL effect comes from the observation that responses can occur after discontinuation of immunosuppression, [7][8][9] after donor lymphocyte infusion 10,11 and after onset of chronic GvHD (cGvHD). 7,[12][13][14] AlloSCT overcomes the poor prognostic impact of fludarabine refractoriness and the presence of deletion(17p)[del (17p)], [1][2][3]8,15,16 and the GvL effect seems to be preserved after reduced intensity conditioning.…”