One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.
Schuster, F R; Hubner, B;  Führer, M;  Eckermann, O; Gombert, M;  Dornmair, K;  Binder, V; Reuther, S; Krell, P;  Keller, T;  Borkhardt, A 
- Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf (Germany)
- Department of Pediatric Oncology and Hematology, Dr von Haunersches Children's Hospital, University of Munich, Munich (Germany)
- Department for Clinical Neuroimmunology, University of Munich, Munich (Germany)
- Acomed, statistical analysis GmbH, Leipzig (Germany)