title: Mixed chimaerism is common at the time of acute graft-versus-host disease and disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation.
abstract: We report the clinical outcome and results of chimaerism analysis in various cell lineages of 30 patients given non-myeloablative conditioning, followed by allogeneic stem cell transplantation (SCT). The commonest diagnoses were chronic myelogenous leukaemia (n = 11) and solid tumours (n = 11). Twenty-one patients received SCT from human leucocyte antigen (HLA)-identical siblings and nine from matched unrelated donors. Median patient age was 53 (28-77) years. Four non-myeloablative protocols were used, including fludarabine (30 mg/m2 x 3-6), busulphan (4 mg/kg x 2), cyclophosphamide (Cy) (30 mg/kg/day x 2) or total body irradiation (2 Gy), and anti-thymocyte globulin. The patients were analysed by polymerase chain reaction (PCR) analysis of minisatellites on days 14, 21 and 28, then every other week up to 3 months and monthly thereafter. All samples were cell separated for T, B and myeloid cells using immunomagnetic beads. Eighteen patients were alive at a median follow-up of 11 (6-20) months. Acute graft-versus-host disease (GVHD) occurred in 22 patients. Eighteen of the 22 patients with acute GVHD showed mixed chimaerism (MC) in the T-cell fraction at the time of acute GVHD. However, all patients with acute GVHD showed donor chimaerism (DC) in the T-cell fraction median 76 (7-414) days after onset versus three out of eight patients without acute GVHD, P < 0.001]. Disease response was diagnosed in 15 patients, median 100 (37-531) days after SCT. At the time of disease response, six out of 15 patients showed MC in the T-cell fraction. In conclusion, mixed chimaerism in the T-cell fraction is common at the time of acute GVHD and disease response in patients conditioned with non-myeloablative therapy.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation and Department of Clinical Immunology, Karolinska Institutet at Huddinge University Hospital, SE-141 86 Stockholm, Sweden. jonas.mattsson@karo.ki.se
authors.forename: J
authors.initials: J
authors.lastname: Mattsson
authors.forename: M
authors.initials: M
authors.lastname: Uzunel
authors.forename: M
authors.initials: M
authors.lastname: Brune
authors.forename: P
authors.initials: P
authors.lastname: Hentschke
authors.forename: L
authors.initials: L
authors.lastname: Barkholt
authors.forename: U
authors.initials: U
authors.lastname: Stierner
authors.forename: J
authors.initials: J
authors.lastname: Aschan
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000473:pathology; D002066:Busulfan / Q000627:therapeutic use; D002452:Cell Count; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine