title: A randomized multicenter comparison of CD34(+)-selected progenitor cells from blood vs from bone marrow in recipients of HLA-identical allogeneic transplants for hematological malignancies.
abstract: OBJECTIVE
  Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone marrow transplantation (BMT) vs PBPC transplantation (PBPCT) using CD34(+) selection for T-cell depletion (TCD) in both study arms.
  
  
  METHODS
  Between January 1996 and October 2000, 120 patients with a diagnosis of acute leukemia, myelodysplasia, multiple myeloma, or lymphoma were randomized to receive either filgrastim-mobilized PBPC or BM from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Patient characteristics did not differ between study arms.
  
  
  RESULTS
  Recipients of PBPC received more CD3(+) T cells (median: 3.0 vs 2.0 x 10(5)/kg, p<0.0001) and more CD34(+) cells (median: 3.6 vs 0.9 x 10(6)/kg, p<0.0001). Neutrophil and platelet recoveries occurred significantly faster after PBPCT. The cumulative incidence of acute GVHD grades II-IV was 37% after BMT vs 52% after PBPCT and was most significantly (p=0.007) affected by the number of CD3(+) T cells in the graft. Acute GVHD appeared strongly associated with increased treatment-related mortality (TRM) in a time-dependent analysis. Higher numbers of CD34(+) cells were associated with less TRM. With a median follow-up of 37 months (range: 12-75), overall survival at 4 years from transplantation was 60% after BMT and 34% for recipients of PBPCT (p=0.04), which difference was largely due to increased GVHD and TRM in PBPC recipients receiving T-cell dosages greater than 2 x 10(5)/kg.
  
  
  CONCLUSIONS
  Outcome following T cell-depleted PBPCT critically depends on the number of CD3(+) T cells, whereby high T-cell numbers may blunt a favorable effect of higher CD34(+) cell numbers.
authors.affiliation: Department of Hematology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. j.cornelissen@erasmusmc.nl
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Eefke J
authors.initials: EJ
authors.lastname: Petersen
authors.forename: Lars
authors.initials: L
authors.lastname: Vindelov
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Russel
authors.forename: Martin
authors.initials: M
authors.lastname: Höglund
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.forename: Monique M C
authors.initials: MM
authors.lastname: Steijaert
authors.forename: Mark J M
authors.initials: MJ
authors.lastname: Zijlmans
authors.forename: Ineke
authors.initials: I
authors.lastname: Slaper-Cortenbach
authors.forename: Marc A
authors.initials: MA
authors.lastname: Boogaerts
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000032:analysis; D002469:Cell Separation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex