title: Favorable preliminary results using TLI/ATG-based immunomodulatory conditioning for matched unrelated donor allogeneic hematopoietic stem cell transplantation in pediatric severe aplastic anemia.
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.
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital Memphis, TN, USA. asha.pillai@stjude.org
authors.forename: Asha
authors.initials: A
authors.lastname: Pillai
authors.forename: Christine
authors.initials: C
authors.lastname: Hartford
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Brandon
authors.initials: B
authors.lastname: Triplett
authors.forename: Mari
authors.initials: M
authors.lastname: Dallas
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000737:chemistry; D001787:Blood Group Incompatibility; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D010372:Pediatrics / Q000379:methods; D012189:Retrospective Studies; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007155:Immunologic Factors; D007166:Immunosuppressive Agents