Mixed chimaerism is associated with poorer long-term failure-free survival among aplastic anaemia patients receiving HLA-matched donor transplantation

Abstract

The aim of this study was to evaluate the adverse effects of mixed chimaerism (MC) on survival outcomes and to assess the ability of different factors to predict MC in severe aplastic anaemia (SAA) patients after HLA-matched donor transplantation. A retrospective study was conducted in 103 consecutive SAA patients who received matched related (MRD) or unrelated donor (MUD) transplantation.The cumulative incidences of mixed chimaerism were 17.8 ± 0.2% and 25.0 ± 0.8% in the MRD and MUD cohorts, respectively (P = 0.432). Patients with mixed chimaerism had signi cantly poorer 10-year failurefree survival (FFS) than those with donor chimaerism (35.0% vs. 87.0%, P < 0.001). A multivariable model identi ed independent adverse predictors of mixed chimaerism, including patient age and ferritin level at transplantation. The incidences of mixed chimaerism were 62.5%, 30.8% and 5.4% in the high-(2 factors), intermediate-(1 factor) and low-risk (0 factor) groups, respectively (P < 0.001). The corresponding FFS rates were 37.5%, 75.3% and 83.6%, respectively (P = 0.018), at the nal follow-up. Therefore, patients with mixed chimaerism suffered poorer long-term FFS, and patients with high-risk scores will be more likely to develop mixed chimaerism. Thus, more intensive conditioning might be recommended for these high-risk patients.

Uniform conditioning regardless of donor in bone marrow transplantation for severe aplastic anemia

“…Additionally, mixed chimerism or late secondary graft failure remain obstacles to longer-term successful outcomes in BMT for SAA. 3 Survival rates following MSD allogeneic BMT have steadily improved since the 1970s largely because of improved supportive care, refined HLA-typing, and better GVHD prophylaxis. 2 However, late BMT-related complications such as chronic GVHD occur in up to one-third of patients, with many of these patients requiring long-term therapy for their GVHD.…”

“…These reduced survival rates are predominantly due to GVHD (which steadily increases with age) and late graft failures. 3 These outcomes remain ripe for improvement.…”