title: Predominant or complete recipient T-cell chimerism following alemtuzumab-based allogeneic transplantation is reversed by donor lymphocytes and not associated with graft failure.
abstract: The clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T-cell depletion. The presence of recipient chimerism levels >40-50% following T-cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor-lymphocyte infusions, but it is unclear whether this finding translates to T-cell depleted transplants. We conducted a retrospective single-institution analysis of patients receiving alemtuzumab-based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T-cell chimerism at 3 months or beyond. By contrast, coincident chimerism in the granulocyte lineage was predominantly of donor origin (median 100%) in all but one patient. Donor lymphocyte infusion effectively converted predominantly recipient T-cell chimerism to ful donor chimerism in all evaluable cases including three cases with no detectable donor T cells. The only graft failure occurred in the patient with predominantly recipient myeloid chimerism in whom rejection occurred rapidly before donor lymphocytes could be administered. We conclude that predominant or complete recipient T-cell chimerism following alemtuzumab-based regimens does not have the same clinical implications as that following T-cell replete transplants and can be effectively converted with donor lymphocytes without the need for lympho-depleting agents or re-conditioning.
authors.affiliation: Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Sajir G
authors.initials: SG
authors.lastname: Mohamedbhai
authors.forename: Noha
authors.initials: N
authors.lastname: Edwards
authors.forename: Emma C
authors.initials: EC
authors.lastname: Morris
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Thomson
authors.forename: Karl S
authors.initials: KS
authors.lastname: Peggs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000628:therapy; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008223:Lymphoma / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects*; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab