title: Minimal GVHD following in-vitro T cell-depleted allogeneic stem cell transplantation with reduced-intensity conditioning allowing subsequent infusions of donor lymphocytes in patients with hematological malignancies and solid tumors.
abstract: OBJECTIVE
  Allogeneic stem cell transplantation (alloSCT) following reduced-intensity conditioning offers a relatively nontoxic regimen while preserving rapid and sustained engraftment. Acute and chronic graft-vs-host disease (GVHD) is, however, a significant cause of severe morbidity. To reduce the incidence of GVHD, we treated a group of high-risk patients with a reduced-intensity conditioning regimen followed by in vitro T-cell-depleted alloSCT using Campath 1-H incubation.
  
  
  METHODS
  Eighteen patients were treated with fludarabine (6 x 30 mg/m(2)), busulphan (2 x 3.2 mg/kg), and ATG (4 x 10 mg/kg) followed by the infusion of high-dose T-cell-depleted peripheral stem cells from sibling donors. No posttransplant GVHD prophylaxis was administered. At 6 months after alloSCT, low-dose donor lymphocyte infusion (DLI) was administered.
  
  
  RESULTS
  All patients had sustained engraftment of donor cells with a median of 95% donor cells at 3 months after alloSCT. Minimal acute and no chronic GVHD was observed after alloSCT. A high incidence of cytomegalovirus (CMV) reactivation but no CMV disease was observed. Eleven patients received DLI at a median of 6.5 months after alloSCT. Acute GVHD grade II-III developed in 6 patients. All patients showed improvement of donor chimerism after DLI. With a median follow-up of 211 days, 11 patients are alive. Particular in patients with chronic lymphocytic leukemia and acute myeloid leukemia, a significant graft-vs-tumor effect was observed.
  
  
  CONCLUSIONS
  In vitro T-cell-depleted alloSCT following reduced-intensity conditioning leads to durable donor engraftment without GVHD. The high levels of donor chimerism allow the subsequent use of cellular immunotherapy to treat residual disease.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. barge.hematology@lumc.nl
authors.forename: Renée M Y
authors.initials: RM
authors.lastname: Barge
authors.forename: Susanne
authors.initials: S
authors.lastname: Osanto
authors.forename: W A F Erik
authors.initials: WA
authors.lastname: Marijt
authors.forename: C W J Ingrid
authors.initials: CW
authors.lastname: Starrenburg
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: J W R Hans
authors.initials: JW
authors.lastname: Nortier
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous