“Real World” Australian Experience of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Adults with Severe Aplastic Anaemia.

Abstract

Acquired Severe Aplastic Anaemia (SAA) is a rare bone marrow failure syndrome, for which allogeneic haematopoietic stem cell transplant (HSCT) is a proven curative therapy. Despite excellent outcomes for matched sibling SAA recipients in terms of engraftment and survival, HSCT remains highly challenging in older matched-unrelated-donor (MUD) recipients, due to increased non-relapse mortality (NRM) from causes such as graft versus host disease (GVHD), organ failure and infection. We sought to evaluate our local HSCT outcomes for SAA, determine factors that predict for inferior outcomes, and benchmark local outcomes against international cohorts. To define outcomes for sibling and MUD HSCT in adults ≥17 years of age with SAA at a single Australian institution between 2002 and 2018 and compare these outcomes to internationally published cohorts. The primary outcome was 1-year overall survival (OS). Secondary outcomes included the incidences of engraftment, response, secondary graft failure, GVHD, and moderate to severe organ dysfunction. All 21 patients comprising 10 sibling and 11 MUD HSCTs, with a median age of 30 (range 17-64), received bone marrow grafts. At a median follow up of 3.5 years, 17 (81%) of 21 patients remained alive and in remission from SAA. 1-year OS, non-relapse mortality (NRM), and GVHD incidence were 85%, 15%, and 48% respectively. Two patients died prior to engraftment at Day+27 and Day+33. When comparing sibling and MUD HSCT recipients, incidences of survival, engraftment and post-HSCT complications were similar; however, MUD HSCT survivors experienced a higher incidence of chronic GVHD (67% vs. 11%; p=0.04). Age >40 years, AKI by Day+28, infection by Day+100 and deviation from intended GVHD prophylaxis predicted for worse OS. Our outcomes following HSCT for SAA are comparable to international cohorts with age >40 years, early onset infection, AKI and deviation from intended GVHD prophylaxis protocol negatively impacting OS. Further research is warranted to optimise MUD HSCT conditioning and GVHD prophylaxis protocols for SAA, particularly in older patients.