title: Excessive T cell depletion of peripheral blood stem cells has an adverse effect upon outcome following allogeneic stem cell transplantation.
abstract: We evaluated the outcome of two modes of T cell depletion for HLA-identical sibling stem cell transplants in 34 consecutive adult patients: group A (n = 11) received PBSC post CliniMACs immuno-magnetic enrichment of CD34(+) cells and group B (n = 23) received bone marrow following in vitro incubation with CAMPATH-1M and complement. All patients received an identical conditioning regimen which consisted of in vivoCAMPATH-1H 20 mg over 5 days, thiotepa 10 mg/kg, cyclophosphamide 120 mg/kg and 14.4 Gy TBI. No additional graft-versus-host disease prophylaxis was given. The mean T cell dose administered was 0.02 +/- 0.05 x 10(6)/kg for group A and 2.8 +/- 2.8 10(6)/kg for group B (P < 0.001). With a median follow-up of 28 months overall survival was 36.4% for group A at 12 months compared to 78.3% for group B (P = 0.001). Transplant-related mortality in group A at 12 months was 63.6% as compared to 18.0% in group B (P = 0.003). Most of the procedure-related deaths in group A occurred secondary to infection. These results suggest that extensive in vitro T cell depletion of peripheral blood stem cells in combination with in vivo T cell depletion may have profound effects upon the incidence of infections following allogeneic stem cell transplantation and this may adversely effect transplant-related mortality.
authors.affiliation: Department of Haematology, University College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Chakraverty
authors.forename: S
authors.initials: S
authors.lastname: Robinson
authors.forename: K
authors.initials: K
authors.lastname: Peggs
authors.forename: P D
authors.initials: PD
authors.lastname: Kottaridis
authors.forename: M J
authors.initials: MJ
authors.lastname: Watts
authors.forename: S J
authors.initials: SJ
authors.lastname: Ings
authors.forename: G
authors.initials: G
authors.lastname: Hale
authors.forename: H
authors.initials: H
authors.lastname: Waldmann
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: S
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D018189:Immunomagnetic Separation; D015994:Incidence; D007239:Infections / Q000209:etiology / Q000401:mortality; D015993:Life Tables; D008212:Lymphocyte Depletion / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab