title: Low transplant mortality in allogeneic bone marrow transplantation for acute myeloid leukemia: a randomized study of low-dose cyclosporin versus low-dose cyclosporin and low-dose methotrexate.
abstract: Sixty patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia (AML) in first remission (CR1; n = 49) or more advanced phase (n = 11) were entered in a prospective trial of graft-versus-host disease (GvHD) prophylaxis: low-dose cyclosporin A (IdCSA; 1 mg/kg/d from day -1 to +20 day; n = 28) or IdCSA plus low-dose methotrexate (IdMTX; 10 mg/m2 for day +1, 8 mg/m2 for days +3, +6, and +11; n = 32). Primary end points were acute GvHD (aGvHD) and transplant-related mortality (TRM); secondary end points were relapse and survival. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and fractionated total body irradiation (3.3 Gy/d for 3 consecutive days). The actuarial risk of developing aGvHD grade II-III was 61% for IdCSA alone and 34% for IdCSA + IdMTX (P = .02). The actuarial risk of TRM at 1 year was 11% versus 13%, respectively, and older patients (>/= 29 years) had higher TRM than younger patients (22% v 5%, P = .01). The age effect was significant in the IdCSA group (P = .04) but not in the IdCSA + IdMTX group (P = .1). The median follow-up is 4.4 years, with an overall actuarial survival of 78% for CR1 patients and 36% for patients with advanced disease. For patients in CR1 the outcome of the two regimens was as follows: survival 77% versus 80% (P = .6), relapse 20% versus 9% (P = .1), and TRM 13% versus 17% (P = .6). This study suggests that TRM can be reduced in AML patients undergoing allogeneic marrow transplants with a mild conditioning regimen and low-dose immunosuppression, and this translates in a 78% 5-year survival for CR1 patients. Beyond CR1 the major obstacle remains leukemia relapse, which is not prevented by low-dose in vivo immunosuppression.
authors.affiliation: Divisione Ematologia II Ospedale San Martino, Istituto Medicina Legale, Universitá, Servizio Radioterapia Istituto Tumori, Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Zikos
authors.forename: M T
authors.initials: MT
authors.lastname: Van Lint
authors.forename: F
authors.initials: F
authors.lastname: Frassoni
authors.forename: T
authors.initials: T
authors.lastname: Lamparelli
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: D
authors.initials: D
authors.lastname: Occhini
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: F
authors.initials: F
authors.lastname: De Stefano
authors.forename: M
authors.initials: M
authors.lastname: Soracco
authors.forename: V
authors.initials: V
authors.lastname: Vitale
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate