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

• Published in: Blood 1998-05, Vol.91 (9), p.3503-3508
• Main Authors: ZIKOS, P, VAN LINT, M. T, SORACCO, M, VITALE, V, BACIGALUPO, A, FRASSONI, F, LAMPARELLI, T, GUALANDI, F, OCCHINI, D, MORDINI, N, BERISSO, G, BREGANTE, S, DE STEFANO, F
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Biological and medical sciences; Bone Marrow Transplantation - methods; Cyclosporine - administration & dosage; Dose-Response Relationship, Drug; Female; Graft vs Host Disease - prevention & control; Humans; Immunomodulators; Immunosuppressive Agents - administration & dosage; Leukemia, Myeloid - therapy; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Pharmacology. Drug treatments; Recurrence; Survival Analysis; Time Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v91.9.3503

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.