| | |  | | | | Record from Web of Science® | | | | | | |
| Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation |
|
|
| Author(s): Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, Fay JW, Nademanee A, Antin JH, Christiansen NP, van der Jagt R, Herzig RH, Litzow MR, Wolff SN, Longo WL, Petersen FB, Karanes C, Avalos B, Storb R, Buell DN, Maher RM, Fitzsimmons WE, Wingard JR |
| Source: BLOOD Volume: 92 Issue: 7 Pages: 2303-2314 Published: OCT 1 1998 |
| Times Cited: 170 References: 55 |
| Abstract: We report the results of a phase III open-label, randomized, multicenter trial comparing tacrolimus/methotrexate to cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis after HLA-identical sibling marrow transplantation in patients with hematologic malignancy. The primary objective of this study was to compare the incidence of moderate to severe (grade II-IV) acute GVHD. Secondary objectives were to compare the relapse rate, disease-free survival, overall survival, and the incidence of chronic GVHD. Patients were stratified according to age (< 40 v greater than or equal to 40) and for male recipients of a marrow graft from an alloimmunized female. There was a significantly greater proportion of patients with advanced disease randomized to tacrolimus arm (P = .02). The incidence of grade Ii-IV acute GVHD was significantly lower in patients who received tacrolimus than patients in the cyclosporine group (31.9% and 44.4%, respectively; P = .01). The incidence of grade Ill-IV acute GVHD was similar, 17.1% in cyclosporine group and 13.3% in the tacrolimus group. There was no difference in the incidence of chronic GVHD between the tacrolimus and the cyclosporine group (55.9% and 49.4%, respectively; P = .8). However, there was a significantly higher proportion of patients in the cyclosporine group who had clinical extensive chronic GVHD (P = .03). The relapse rates of the two groups were similar. The patients in the cyclosporine arm had a significantly better 2-year disease-free survival and overall survival than patients in the tacrolimus arm, 50.4% versus 40.5% (P = .01) and 57.2% versus 46.9% (P = .02), respectively. The significant difference in the overall and disease-free survival was largely the result of the patients with advanced disease, 24.8% with tacrolimus versus 41.7% with cyclosporine (P = .006) and 20.4% with tacrolimus versus 28% with cyclosporine (P = .007), respectively. There was a higher frequency of deaths from regimen-related toxicity in patients with advanced disease who received tacrolimus. There was no difference in the disease-free and overall survival in patients with nonadvanced disease. These results show the superiority of tacrolimus/methotrexate over cyclosporine/methotrexate in the prevention of grade Ii-IV acute GVHD with no difference in disease-free or overall survival in patients with nonadvanced disease. The survival disadvantage in advanced disease patients receiving tacrolimus warrants further investigation. (C) 1998 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
| Reprint Address: Ratanatharathorn, V (reprint author), Univ Michigan, Med Ctr, Ctr Canc B1207, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA |
Addresses:
1. Univ Michigan, Med Ctr, Ctr Canc B1207, Ann Arbor, MI 48109 USA
2. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA
3. Lutheran Gen Hosp, Chicago, IL USA
4. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA
5. Wayne State Univ, Detroit, MI USA
6. Univ Minnesota, Minneapolis, MN 55455 USA
7. Baylor Univ, Med Ctr, Dallas, TX USA
8. City Hope Natl Med Ctr, Duarte, CA 91010 USA
9. Brigham & Womens Hosp, Boston, MA 02115 USA
10. Ohio State Univ, Columbus, OH 43210 USA
11. Ottawa Gen Hosp, Ottawa, ON K1H 8L6 Canada
12. New York State Dept Hlth, Roswell Pk Mem Inst, Buffalo, NY 14263 USA
13. Univ Louisville, Louisville, KY 40292 USA
14. Mayo Clin, Rochester, MN USA
15. Vanderbilt Univ, Med Ctr, Nashville, TN USA
16. Univ Wisconsin, Madison, WI 53706 USA
17. Univ Utah, Salt Lake City, UT USA
18. Fujisawa USA, Deerfield, IL USA
19. Univ Florida, Gainesville, FL USA |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA |
| Subject Category: Hematology |
| IDS Number: 123FN |
| ISSN: 0006-4971 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |