title: Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia.
abstract: 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.
authors: F R
authors: FR
authors: Schuster
authors: B
authors: B
authors: Hubner
authors: M
authors: M
authors: Führer
authors: O
authors: O
authors: Eckermann
authors: M
authors: M
authors: Gombert
authors: K
authors: K
authors: Dornmair
authors: V
authors: V
authors: Binder
authors: S
authors: S
authors: Reuther
authors: P
authors: P
authors: Krell
authors: T
authors: T
authors: Keller
authors: A
authors: A
authors: Borkhardt