title: Reduced-intensity conditioning followed by allografting of CD34-selected stem cells and < or =10(6)/kg T cells may have an adverse effect on transplant-related mortality.
abstract: In patients undergoing allogeneic peripheral blood stem cell (PBSC) transplantation after reduced-intensity conditioning (RIC), graft-versus-host disease (GVHD) represents a major cause of morbidity and mortality. T-cell depletion (TCD) prevents GVHD but carries potential risks of graft failure, opportunistic infections, and disease relapse. We explored ex vivo TCD of stem cell allografts that were administered after RIC treatment. Thirteen high-risk patients with hematological malignancies were treated with a fludarabine/melphalan-based RIC regimen followed by transplantation of immunomagnetically selected CD34(+) PBSC from HLA-identical sibling or matched unrelated donors. Patients were sequentially enrolled in two cohorts: group A (n=6) received antithymocyte globulin (ATG) during conditioning and 10(5) donor T cells/kg at transplantation, while group B (n=7) received 10(6) donor T cells/kg without ATG pretreatment. Primary graft failure occurred in two patients of group A and in one patient of group B. Complete donor chimerism persisting more than 1 year was achieved in two cases per cohort. Acute grade II to IV or chronic extensive GVHD were observed in a total of six patients (group A, 2; group B, 4). Procedure-related deaths were mainly due to severe pneumonia occurring in two patients of group A and in five patients of group B. These results suggest that CD34 selection of reduced-intensity PBSC allografts may cause adverse effects upon specific antimicrobial immunity which can lead to fatal infections, particularly in high-risk patients. In our study, simultaneous add-back of < or =10(6)/kg donor T cells was unable to compensate for this deficiency.
authors.affiliation: Department of Medicine III, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Udo F
authors.initials: UF
authors.lastname: Hartwig
authors.forename: Nils
authors.initials: N
authors.lastname: Winkelmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Wehler
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreiter
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Karin
authors.initials: K
authors.lastname: Kolbe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D002458:Cell Fractionation; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000382:microbiology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009894:Opportunistic Infections / Q000382:microbiology / Q000401:mortality; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000401:mortality; D013601:T-Lymphocytes / Q000637:transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan