title: Patterns and kinetics of T-cell chimerism after allo transplant with alemtuzumab-based conditioning: mixed chimerism protects from GVHD, but does not portend disease recurrence.
abstract: We analyzed the kinetics of CD3 chimerism in 120 consecutive allogeneic hematopoietic cell transplantation (HCT) recipients receiving alemtuzumab-based conditioning. Fifty-two received fludarabine/melphalan, 44 received fludarabine/busulfan, and 24 received clofarabine/melphalan in addition to alemtuzumab. Post-transplant GVHD prophylaxis consisted of tacrolimus. No prophylactic donor lymphocyte infusion or other interventions were used for mixed donor chimerism (MDC). Bone marrow (BM) and/or peripheral blood (PB) samples were obtained at 30 days, 100 days, 180 days, and 1 year following HCT. On Day 30, 15% of assessable patients had MDC in the CD3 compartment. This had increased to 50% by Day 100, and to 63% by Day 180. MDC predicted for a lower risk of acute (p = 0.08) and particularly of chronic GVHD (p = 0.01). MDC was not associated with subsequent relapse or TRM (p = 0.67 and 0.72, respectively). A decline of more than 15% in CD3 chimerism between Day 30 and Day 180 predicted for a 40% risk of subsequent disease recurrence. The observation of MDC after alemtuzumab conditioning does not by itself constitute a risk factor for relapse and should not be used to guide therapeutic intervention. By contrast, declining donor chimerism between Day 30 and Day 180 is associated with a somewhat increased risk of disease recurrence. The high incidence of MDC after alemtuzumab containing conditioning contributes to the low risk of acute and chronic GVHD.
authors.affiliation: Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA. kvbesien@uchicago.edu
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.forename: Alexander
authors.initials: A
authors.lastname: Dew
authors.forename: Shang
authors.initials: S
authors.lastname: Lin
authors.forename: Loren
authors.initials: L
authors.lastname: Joseph
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Toyosi
authors.initials: T
authors.lastname: Odenike
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rich
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Amittha
authors.initials: A
authors.lastname: Wickrema
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Artz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017252:CD3 Complex / Q000097:blood; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000628:therapy; D008223:Lymphoma / Q000097:blood / Q000628:therapy; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D017252:CD3 Complex; D000074323:Alemtuzumab; D016559:Tacrolimus