title: Fractionated TBI correlates with less T cell mixed chimerism but increased risk of relapse compared to busulphan in patients with haematological malignancies after allogeneic stem cell transplantation.
abstract: We prospectively evaluated mixed chimerism (MC) in the T cell and myeloid lineages and its correlation to busulphan, single-dose total body irradiation (TBI) and fractionated TBI (fTBI) conditioning in 180 patients with haematological malignancies after allogeneic stem cell transplantation (SCT). In all patients receiving busulphan, the area under curve (AUC) was calculated. The incidence of MC in the T cell lineage was significantly lower in patients receiving fTBI (22%) compared to those given TBI (53%, P=0.02) or busulphan (47%, P<0.01). The incidence of myeloid MC did not differ between the three groups. The overall probability of acute graft-versus-host disease grades II-IV was significantly higher in patients with complete T cell donor chimerism (49%) compared to patients with T cell MC (23%, P<0.001). The incidence of T cell and myeloid MC after SCT did not differ between low (55%), medium (42%) and high (43%) AUC levels of busulphan during conditioning. Patients receiving fTBI had a significantly higher probability of relapse compared to busulphan-treated patients (44 vs l6%, P=0.01). In multivariate analysis adjusted for diagnosis, busulphan-treated patients showed both a better survival (P=0.04) and less probability of relapse (0.03) compared to TBI-treated patients.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
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: Remberger
authors.forename: M
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D019583:Dose Fractionation, Radiation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D022423:Myeloid Cells; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis; D013601:T-Lymphocytes; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D002066:Busulfan