title: The combined effect of total body irradiation (TBI) and cyclosporin A (CyA) on the risk of relapse in patients with acute myeloid leukaemia undergoing allogeneic bone marrow transplantation.
abstract: One hundred and fifty acute myeloid leukaemia (AML) patients in first remission received an allogeneic bone marrow transplant (BMT), after conditioning with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 3.3 Gy x 3 (total nominal dose 9.9). The received dose, as recorded by thermoluminescent dosimeters, ranged between 7. 83 and 12.25 Gy. Patients who received TBI < 9.9 Gy (n = 34) had a significantly higher relapse rate when compared with patients receiving >/= 9.9 Gy (n = 116) (43% vs. 19%; P = 0.002). Graft versus host disease (GvHD) prophylaxis consisted of cyclosporin A (CyA) with or without methotrexate (MTX). The dose of CyA was either 1 or 5 mg/kg/day i.v. from day -1 to + 20, then 10 mg/kg/day orally until day + 365. Patients receiving 5 mg/kg CyA (n = 40) had a higher risk of relapse (49% vs. 15%; P = 0.0001). Thus, low-dose TBI (< 9.9 Gy) and high-dose CyA (5 mg/kg) were significant predictors of leukaemia relapse. Patients were then divided into three groups: those who had both negative predictors (< 9.9 Gy TBI and 5 mg/kg CyA; n = 26); those who had only one (either < 9.9 Gy TBI or 5 mg/kg CyA; n = 22); and those who had neither (>/= 9.9 Gy TBI and 1 mg/kg CyA; n = 102). The three groups were comparable for FAB subtype, interval diagnosis transplant and age. The 5-year actuarial relapse rate for these three groups of patients was 49%, 41% and 15%, with no difference between the first two and a significant difference when compared with the latter (P < 0.01). These data indicate that acute myeloid leukaemia can be cured with allogeneic bone marrow transplantation given an intensive conditioning regimen and low-dose immunosuppression post-graft. Either alone is insufficient to produce long-term disease-free survival. These results may be relevant for programmes of reduced intensity conditioning designed for patients with acute leukaemia.
authors.affiliation: Divisione Ematologia II Ospedale San Martino and Istituto Scientifico Tumori, Servizio Radioterapia Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: V
authors.initials: V
authors.lastname: Vitale
authors.forename: R
authors.initials: R
authors.lastname: Corvò
authors.forename: S
authors.initials: S
authors.lastname: Barra
authors.forename: T
authors.initials: T
authors.lastname: Lamparelli
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: N
authors.initials: N
authors.lastname: Mordini
authors.forename: G
authors.initials: G
authors.lastname: Berisso
authors.forename: S
authors.initials: S
authors.lastname: Bregante
authors.forename: A M
authors.initials: AM
authors.lastname: Raiola
authors.forename: M T
authors.initials: MT
authors.lastname: Van Lint
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000628:therapy*; D012008:Recurrence; D012307:Risk Factors; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation / Q000379:methods*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine