Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil

Severe aplastic anaemia (SAA) can be successfully treated with immunosuppressive therapies or haematopoietic stem cell transplantation (HSCT). Response rates with horse anti-thymocyte globulin (h-ATG) plus ciclosporin (CsA) are about 60-70%, and robust responders have an excellent long-term survival. We introduced a third immunosuppressive agent to standard h-ATG/CsA, mycophenolate mofetil (MMF), in an attempt to improve the response rate and survival, and to decrease the relapse rate and clonal evolution to myelodysplasia. A total of 104 consecutive patients with SAA were treated with h-ATG/CsA/MMF between May 1999 and June 2003 at the National Institutes of Health Clinical Center. The overall response rate at 6 months was 62%, with 24 (37% of responders) patients relapsing at a median of 389 d from ATG. Nine patients showed evidence of clonal evolution following ATG. After a median follow up of 42 months, the median survival among responders was not reached and among non-responders was 58 months. Over half of the relapses occurred during MMF administration. Despite a strong theoretical rationale for its use, MMF did not result in the improvement of response or relapse rates when compared with historical standard h-ATG/CsA.