title: Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation.
  
  
  METHODS
  The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed.
  
  
  RESULTS
  Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI-based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome.
  
  
  CONCLUSIONS
  In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival.
authors.affiliation: Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Heinzelmann
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lang
authors.forename: Hellmut
authors.initials: H
authors.lastname: Ottinger
authors.forename: Christoph
authors.initials: C
authors.lastname: Faul
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bethge
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Michael
authors.initials: M
authors.lastname: Bamberg
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006084:Graft Rejection / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015182:Lymphatic Irradiation / Q000379:methods* / Q000401:mortality; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D011014:Pneumonia / Q000209:etiology; D019233:Retreatment / Q000379:methods; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D014740:Vidarabine; C024352:fludarabine