Impact of ACAs on allo-HSCT outcomes in Ph+ ALL following TKI therapy

Results from a retrospective, registry-based analysis of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT) comparing transplantation outcomes in adults with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with (n = 345) vs without (n = 169) additional chromosomal abnormalities (ACAs) who received a tyrosine kinase inhibitor (TKI) prior to allogeneic hematopoietic stem cell transplant (allo-HSCT) were published in Bone Marrow Transplantation by Nagler et al. The aim of this study was to evaluate the impact of ACAs on allo-HSCT outcomes. 

Key data: The 4-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease relapse-free survival (GRFS) rates were 67.7% vs 65.4%, 76.3% vs 78.5%, and 48.5% vs 45.1% in the ACAs vs no ACAs groups, respectively. The presence of ACAs was associated with a significantly higher rate of measurable residual disease (MRD)-negativity before allo-HSCT (p = 0.04). In multivariable analysis, the presence and number of ACAs did not significantly affect any transplant outcome. MRD-positivity pre-allo-HSCT was associated with worse LFS (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.01–1.91; p = 0.04) and OS (HR, 1.54; 95% CI, 1.04–2.27; p = 0.03), as well as higher non-relapse mortality (NRM; HR, 1.68; 95% CI, 1.02–2.76; p = 0.04).

Key learning: TKI therapy followed by allo-HSCT may overcome the adverse prognostic impact of ACAs in Ph+ ALL, with MRD negativity prior to transplantation remaining an important prognostic goal.