Outcome Of Aplastic Anemia In Adolescence. A Survey Of The Severe Aplastic Anemia Working Party (SAAWP) Of The European Blood and Bone Marrow Transplant Group (EBMT)

We analyzed the outcome according to different treatments of 537 adolescents (age 12-18 years) with acquired aplastic anemia from the data-base of the SAAWP of the EBMT.

OS after front-line matched family donor (MFD) hematopoietic stem cell transplantation (HSCT) was 86% whereas after front-line immunosuppressive therapy (IST) was 82% (p= 0.53). EFS (events being death, relapse/no response, PNH/MDS/AML evolution, transplant) was 83% after MFD HSCT and 37% after IST (p=0.0001).

To evaluate the outcome of adolescents who were transplanted after failure of IST upfront (HSCT after failed IST) we extrapolated these patients from the original population receiving front-line immunosuppression and compared with those undergoing MFD HSCT upfront and IST upfront but who were not subsequently transplanted (IST up-front alone in whom transplant was not an event). OS in MFD HSCT was 86%, in IST up-front alone 90% and in HSCT post failed IST 78% (p=0.14). EFS was respectively 83%, 64% and 71% (p= 0.04) with no difference in post hoc analysis between IST alone and HSCT post IST (p=0.17). In the transplanted population, OS and EFS were significantly higher with bone marrow vs peripheral blood as source of cells. No differences in OS and EFS were seen in patients transplanted in adult, pediatric or mixed centres.

Cumulative incidence (CI) of rejection was 8 % in MFD HSCT and 9% in HSCT post failed IST (p=0.62). CI of Ac GVHD was 12% in MDF HSCT and 18% in HSCT post failed IST (p=0.18). CI of Chronic GVHD was 8% in MFD HSCT and 20% in HSCT post failed IST (p=0.0009). CI of secondary malignancies was 0.7% in MDF HSCT, 7% in HSCT post-failed IST and 21% after IST up-front alone (p= 0.0017).

In the whole cohort in multivariate analysis, the diagnosis to treatment interval of ≤2 months positively affected OS whereas IST alone negatively affected EFS. In transplanted patients interval diagnosis-treatment ≤2 months, first line MDF HSCT and BM as source of cells provided a significant advantage in OS and EFS. Aplastic anemia in adolescents has a very good outcome. If a MFD is available, HSCT using BM cells is the first choice treatment. If a MFD is not available, IST looks a reasonable second choice. If IST fails HSCT represents a very good rescue option.