The European landscape on allogeneic haematopoeietic cell transplantation in Chronic Lymphocytic Leukaemia between 2009 and 2019: a perspective from the Chronic Malignancies Working Party of the EBMT

Abstract

Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness.

Fig. 1. Number and incidence of allo-HCT for CLL in the 2009-2019 EBMT registry.

a Number of first allo-HCT procedures for CLL patients older than 18 years, recorded in the EBMT registry between 2009 to 2019. Blue line: total number of allo-HCT; orange line: number of allo-HCT performed on the 10 countries who performed more than 50 allo-HCT during this period; grey line: number of allo-HCT performed on the remaining countries who performed less than 50 allo-HCT during this period. b Annual incidence of CLL transplants per year and per 10 million inhabitants recorded in the EBMT registry in the 10 countries who performed more than 50 allo-HCT between 2009 and 2019.

Fig. 2. Outcomes of allo-HCT for CLL in the 2009-2019 EBMT registry.

Kaplan-Meier survival curves of (a) Overall Survival (OS) and (b) Progression Free Survival (PFS) within the first 10 years after allo-HCT. The shaded regions indicate the 95% confidence intervals. The number of event free patients are indicated below the time axis. Estimates of OS and PFS including 95% CI by 3 and 5 years are given (vertical dotted lines) in (a, b) respectively.