Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation

Abstract

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

Mature lymphoid malignancies: origin, stem cells, and chronicity

“…Conversely, late relapses are rarely seen after allogeneic transplantation for lymphoma and CLL, with very few patients relapsing after 2 years and nice survival curve plateaus. [104][105][106][107][108] This points to myeloablative therapy and graft-versus-tumor effect indeed are sufficient to eliminate residual premalignant cells. However, the side effects of allogeneic HSC transplantation restricts its use to second-line treatment (or later) and is mainly suitable for fit, younger patients with relapsed chemosensitive disease.…”

Anti‐CD20 immunotherapy as a bridge to tolerance, after allogeneic stem cell transplantation for patients with chronic lymphocytic leukaemia: results of the CLLX4 trial

“…Treatment failure after allogeneic haematopoietic cell transplantation (HCT) in patients with high risk chronic lymphocytic leukaemia (CLL) is almost equally distributed between relapse and non‐relapse mortality (van Gelder et al , ). Pre‐clinical and clinical evidence suggests anti‐CD20 immunotherapy may be promising for the prevention and treatment of chronic graft‐versus‐host disease (GVHD) (Kharfan‐Dabaja & Cutler, ; Zeiser & Blazar, ).…”

“…Some patients, however, will be lost during sequential treatment due to Richter transformation and/or infectious complications (Mato et al , ; Jones et al , ). Given the sustained disease control after alloHCT in a significant percentage of patients, recommendation of alloHCT to good risk transplant candidates who are refractory or intolerant to either BTK‐ or BCL2‐inhibition may still be a wise clinical decision (van Gelder et al , ; Schetelig et al , ).…”

Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

“…In several retrospective registry studies 5-year PFS and overall survival (OS) after alloHCT for CLL were 36 to 46% [13,14]. In most patients in these studies HLAidentical donors were used.…”