Early emergence of PNH-like T cells after allogeneic stem cell transplants utilising CAMPATH-1H for T cell depletion.
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.
Garland
R J
RJ
Department of Pathology and Microbiology, University of Bristol, University Walk, Bristol, UK. R.Garland@bristol.ac.uk
Groves
S J
SJ
Diamanti
P
P
West
S E
SE
Winship
K L
KL
Virgo
P F
PF
Robinson
S P
SP
Oakhill
A
A
Cornish
J M
JM
Pamphilon
D H
DH
Marks
D I
DI
Goulden
N J
NJ
Steward
C G
CG
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
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