Methotrexate and Cyclosporine Versus Cyclosporine Alone for Prophylaxis of Graft-Versus-Host Disease in Patients Given HLA-identical Marrow Grafts for Leukemia: Long-Term Follow-up of a Controlled Trial

• Published in: Blood Vol. 73; no. 6; pp. 1729 - 1734
• Main Authors: Storb, Rainer, Deeg, H.Joachim, Pepe, Margaret, Appelbaum, Frederick, Anasetti, Claudio, Beatty, Patrick, Bensinger, William, Berenson, Ronald, Buckner, C.Dean, Clift, Reginald, Doney, Kris, Longton, Gary, Hansen, John, Hill, Roger, Jr, Thomas Loughran, Martin, Paul, Singer, Jack, Sanders, Jean, Stewart, Patricia, Sullivan, Keith, Witherspoon, Robert, Thomas, E.Donnall
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.05.1989; The Americain Society of Hematology
• Subjects: Acute Disease; Biological and medical sciences; Bone Marrow Transplantation; Chronic Disease; Cyclosporins - administration & dosage; Drug Therapy, Combination; Follow-Up Studies; Graft vs Host Disease - prevention & control; HLA Antigens - analysis; Humans; Immunomodulators; Leukemia - therapy; Medical sciences; Methotrexate - administration & dosage; Pharmacology. Drug treatments; Prognosis; Time Factors; Antineoplastic agent; Human; Drug combination; Intravenous administration; Leukemia; Graft versus host reaction; Hemopathy; Radiotherapy; Prevention; Chemotherapy; Treatment; Bone marrow; Graft; Immunosuppressive agent
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V73.6.1729.1729

Patients with acute nonlymphoblastic leukemia (ANL) in first remission (n = 38) or chronic myelocytic leukemia (CML) (n = 55) were given cyclophosphamide and total body irradiation, followed by marrow infusion from HLA-identical siblings. To evaluate postgrafting prophylaxis for acute graft-versus-host disease (GVHD), the patients were randomized to receive either methotrexate and cyclosporine (n = 43) or cyclosporine alone (n = 50). Methotrexate/cyclosporine significantly reduced the incidence and severity of acute GVHD, and improved early survival. This report updates the results with a 3.0 to 4.5 year follow-up. Methotrexate/cyclosporine did not interfere with sustained hematopoietic engraftment, although granulocyte recovery to 1,000/μL was delayed by five days on the average. The incidence of chronic GVHD was identical in the two groups (26% v 24%). Disease-free 3-year survival was slightly better in the methotrexate/cyclosporine group (65% v 54%), but this benefit was restricted to patients with CML (73% v 54%), while no improvement was seen in patients with ANL (41% v 41%). In contrast to patients with CML (relapse rates 8% v 9%), the early survival benefit among patients with ANL given methotrexate/cyclosporine was offset by an increase in leukemic relapses (29% v 16%).