title: Early emergence of PNH-like T cells after allogeneic stem cell transplants utilising CAMPATH-1H for T cell depletion.
abstract: CAMPATH-1H (C-1H) is widely used in vivo and / or in vitro for T cell depletion in hematopoietic SCT. This humanised monoclonal antibody is specific for CD52, a marker coexpressed on the majority of human lymphocytes with CD48 and other glycosylphosphatidyl-inositol (GPI) anchored proteins. We detected CD52 / CD48 dual expression on >99% of CD3(+) lymphocytes from normal individuals and all 15 post-SCT patients whose transplants did not utilise C-1H. By contrast, 23 / 26 patients with transplants involving C-1H (in vivo, in vitro or both) exhibited populations lacking CD52 expression that accounted for 49.7% (4.2-86.2%) of the CD3+ lymphocytes (median and range) in samples evaluated at a median of 2 months post-SCT. Most CD52- cells also lacked CD48 expression. These GPI- T cells were of either donor or mixed donor / recipient origin. They were predominant in the early months after SCT at times of profound lymphopenia and inversely correlated with the recovery of the absolute lymphocyte count (r= - 0.663, P<0.0001). The presence of CD52- cells has been correlated previously with clinical outcome after CAMPATH therapy for both malignant and nonmalignant diseases.
authors.affiliation: Department of Pathology and Microbiology, University of Bristol, University Walk, Bristol, UK. R.Garland@bristol.ac.uk
authors.forename: R J
authors.initials: RJ
authors.lastname: Garland
authors.forename: S J
authors.initials: SJ
authors.lastname: Groves
authors.forename: P
authors.initials: P
authors.lastname: Diamanti
authors.forename: S E
authors.initials: SE
authors.lastname: West
authors.forename: K L
authors.initials: KL
authors.lastname: Winship
authors.forename: P F
authors.initials: PF
authors.lastname: Virgo
authors.forename: S P
authors.initials: SP
authors.lastname: Robinson
authors.forename: A
authors.initials: A
authors.lastname: Oakhill
authors.forename: J M
authors.initials: JM
authors.lastname: Cornish
authors.forename: D H
authors.initials: DH
authors.lastname: Pamphilon
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.forename: N J
authors.initials: NJ
authors.lastname: Goulden
authors.forename: C G
authors.initials: CG
authors.lastname: Steward
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000737:chemistry*; D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017252:CD3 Complex / Q000096:biosynthesis; D000071178:CD48 Antigen; D000074301:CD52 Antigen; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000378:metabolism*; D006801:Humans; D018189:Immunomagnetic Separation; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D017252:CD3 Complex; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D000074323:Alemtuzumab