title: Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning.
abstract: Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days -16 and -15, fludarabine 30 mg/m(2) per day on day -7 through -3, IV busulfan 130 mg/m(2) per day on days -4 and -3 and cyclophosphamide 1500 mg/m(2) on day -2. rATG levels were therapeutic in all patients on day -14, but were sub-therapeutic (<1 μg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75-100%) and 100% (90-100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II-IV and III-IV were 39 and 9%. Median follow-up is 64 months (46-79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: M
authors: M
authors: Sanacore
authors: Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA.
authors: X
authors: X
authors: Zhang
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: S L
authors: SL
authors: Brown
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: K
authors: K
authors: Connor
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: S
authors: S
authors: Hilton
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: L E
authors: LE
authors: Morris
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: H K
authors: HK
authors: Holland
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: S R
authors: SR
authors: Solomon
authors: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
authors: A
authors: A
authors: Bashey
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D015996:Survival Rate; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine