title: Low-dose total-body irradiation and fludarabine followed by hematopoietic cell transplantation from HLA-identical sibling donors do not induce complete T-cell donor engraftment in most patients with progressive hematologic diseases.
abstract: OBJECTIVE
  The aim of this study was to determine whether nonmyeloablative transplants (NMT) result in complete and sustained donor engraftment in patients with progressive hematologic diseases compared to patients with stable disease or who are in remission.
  
  
  METHODS
  We prospectively monitored the kinetics of engrafting of T cells and myeloid cells in 10 consecutive adult patients with hematologic diseases submitted to NMT from an HLA-identical sibling donor. Patients were considered ineligible for conventional allogeneic transplantation because of age, concomitant diseases, or previous autologous transplant. Conditioning regimen and graft-vs-host disease posttransplant prophylaxis consisted of 2-Gy total-body irradiation plus fludarabine 30 mg/m(2)/day for 3 days, and cyclosporin and mycophenolate mofetil, respectively.
  
  
  RESULTS
  One patient died in remission, and eight relapsed or progressed at a median of 68 days (15-335). On day +56, only 1 (11%) of 9 patients analyzed had achieved T-cell complete donor chimerism (CC), whereas 6 (67%) had achieved myeloid CC (p=0.05). Median time for T-cell CC to occur was 110 days (56-150) compared with 42 days (28-100) to achieve myeloid CC (p=0.002). The only parameter associated with T-cell CC was the status of the disease at the time of transplantation. Thus, 5 (100%) of 5 patients with stable disease or who were in remission before the transplant achieved T-cell CC compared with only 1 (20%) of 5 patients with progressive disease (p=0.05).
  
  
  CONCLUSIONS
  Conditioning regimen based on fludarabine and 2-Gy total-body irradiation allows cell immunotherapy for old and medically infirm patients, but its antitumoral effect in patients with progressive hematologic disease is limited.
authors.affiliation: Institute of Hematology and Oncology, IDIBAPS, Postgraduate School of Hematology Farreras Valentí, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Fernández-Avilés
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Carme
authors.initials: C
authors.lastname: Talarn
authors.forename: Mónica
authors.initials: M
authors.lastname: Jiménez
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D020544:Graft vs Leukemia Effect; D006402:Hematologic Diseases / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000637:transplantation; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014916:Whole-Body Irradiation
chemical_list: D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine