Favorable preliminary results using TLI/ATG-based immunomodulatory conditioning for matched unrelated donor allogeneic hematopoietic stem cell transplantation in pediatric severe aplastic anemia

Pediatr Transplant. 2011 Sep;15(6):628-34. doi: 10.1111/j.1399-3046.2011.01542.x. Epub 2011 Jul 15.

Abstract

To assess whether a tolerance-induction regimen could be applied for unrelated (MUD) HCT in SAA, we retrospectively reviewed our HCT experience using unmanipulated 10/10 HLA-matched bone marrow grafts from MSD vs. MUD donors. Conditioning was CTX 200 mg/kg (CTX) + rabbit ATG 10 mg/kg (ATG) for MSD (n = 9) and TLI (800 cGy) + CTX/ATG for MUD HCT ( n = 5). Immunoprophylaxis was CSA and short-course MTX. Median patient age was 14.7 yr, median time to HCT 1.5 yr, and median follow-up 3 yr. Outcome measures included EFS, time to engraftment, and cumulative incidence of GVHD (CIN of GVHD) for MSD and MUD cohorts. EFS and stable engraftment rate were 100%. CIN of acute GVHD was: MSD, Grade I-II: 1 (11%), Grade III-IV: 0%; MUD, Grade I-II: 1 (20%), Grade III-IV: 1 (20%). CIN of chronic GVHD was: MSD, limited: 1 (11%), extensive: 0%; MUD, limited: 0%, extensive: 0%. All immunosuppressive-compliant patients successfully weaned immunosuppression. Although in limited patients, our results suggest that immunomodulatory TLI added to backbone CTX/ATG conditioning is a promising option for MUD HCT in SAA patients, which we will examine in a prospective clinical trial.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Aplastic / therapy*
  • Antilymphocyte Serum / chemistry
  • Blood Group Incompatibility
  • Bone Marrow Transplantation
  • Child
  • Child, Preschool
  • Female
  • HLA Antigens / metabolism
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunologic Factors / metabolism*
  • Immunosuppressive Agents / therapeutic use
  • Lymphocytes / radiation effects
  • Male
  • Pediatrics / methods
  • Retrospective Studies
  • Transplantation Conditioning
  • Transplantation Tolerance
  • Treatment Outcome

Substances

  • Antilymphocyte Serum
  • HLA Antigens
  • Immunologic Factors
  • Immunosuppressive Agents