Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors

R. A. Nash, J. H. Antin, C. Karanes, J. W. Fay, B. R. Avalos, Andrew M Yeager, D. Przepiorka, S. Davies, F. B. Petersen, P. Bartels, D. Buell, W. Fitzsimmons, C. Anasetti, R. Storb, V. Ratanatharathorn

Research output: Contribution to journalArticle

417 Citations (Scopus)

Abstract

After the transplantation of unmodified marrow from human leukocyte antigen-matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75%. Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was etfective in combination with MTX for the prevention of acute GVHD. Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors. There was a significant trend toward decreased severity of acute GVHD across all grades (P = .005). Based on the Kaplan-Meier estimate, the probability of grade IMV acute GVHD in the tacrolimus group (56%) was significantly lower than in the CSP group (74%; P = .0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65% vs 81%, respectively; P = .019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8). Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54% versus 50% (P = .46) and 47% versus 42% (P = .58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2062-2068
Number of pages7
JournalBlood
Volume96
Issue number6
StatePublished - Sep 15 2000
Externally publishedYes

Fingerprint

Transplantation (surgical)
Unrelated Donors
Tacrolimus
Graft vs Host Disease
Methotrexate
Grafts
Cyclosporine
Transplantation
Bone Marrow
Recurrence
Dialysis
Incidence
Macrolides
Kaplan-Meier Estimate
HLA Antigens
Glucocorticoids
Multicenter Studies
Toxicity
Labels
Leukemia

ASJC Scopus subject areas

  • Hematology

Cite this

Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. / Nash, R. A.; Antin, J. H.; Karanes, C.; Fay, J. W.; Avalos, B. R.; Yeager, Andrew M; Przepiorka, D.; Davies, S.; Petersen, F. B.; Bartels, P.; Buell, D.; Fitzsimmons, W.; Anasetti, C.; Storb, R.; Ratanatharathorn, V.

In: Blood, Vol. 96, No. 6, 15.09.2000, p. 2062-2068.

Research output: Contribution to journalArticle

Nash, RA, Antin, JH, Karanes, C, Fay, JW, Avalos, BR, Yeager, AM, Przepiorka, D, Davies, S, Petersen, FB, Bartels, P, Buell, D, Fitzsimmons, W, Anasetti, C, Storb, R & Ratanatharathorn, V 2000, 'Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors', Blood, vol. 96, no. 6, pp. 2062-2068.
Nash, R. A. ; Antin, J. H. ; Karanes, C. ; Fay, J. W. ; Avalos, B. R. ; Yeager, Andrew M ; Przepiorka, D. ; Davies, S. ; Petersen, F. B. ; Bartels, P. ; Buell, D. ; Fitzsimmons, W. ; Anasetti, C. ; Storb, R. ; Ratanatharathorn, V. / Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. In: Blood. 2000 ; Vol. 96, No. 6. pp. 2062-2068.
@article{8b6d699ce19e45c99e61353100b5323a,
title = "Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors",
abstract = "After the transplantation of unmodified marrow from human leukocyte antigen-matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75{\%}. Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was etfective in combination with MTX for the prevention of acute GVHD. Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors. There was a significant trend toward decreased severity of acute GVHD across all grades (P = .005). Based on the Kaplan-Meier estimate, the probability of grade IMV acute GVHD in the tacrolimus group (56{\%}) was significantly lower than in the CSP group (74{\%}; P = .0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65{\%} vs 81{\%}, respectively; P = .019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8). Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54{\%} versus 50{\%} (P = .46) and 47{\%} versus 42{\%} (P = .58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse. (C) 2000 by The American Society of Hematology.",
author = "Nash, {R. A.} and Antin, {J. H.} and C. Karanes and Fay, {J. W.} and Avalos, {B. R.} and Yeager, {Andrew M} and D. Przepiorka and S. Davies and Petersen, {F. B.} and P. Bartels and D. Buell and W. Fitzsimmons and C. Anasetti and R. Storb and V. Ratanatharathorn",
year = "2000",
month = "9",
day = "15",
language = "English (US)",
volume = "96",
pages = "2062--2068",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors

AU - Nash, R. A.

AU - Antin, J. H.

AU - Karanes, C.

AU - Fay, J. W.

AU - Avalos, B. R.

AU - Yeager, Andrew M

AU - Przepiorka, D.

AU - Davies, S.

AU - Petersen, F. B.

AU - Bartels, P.

AU - Buell, D.

AU - Fitzsimmons, W.

AU - Anasetti, C.

AU - Storb, R.

AU - Ratanatharathorn, V.

PY - 2000/9/15

Y1 - 2000/9/15

N2 - After the transplantation of unmodified marrow from human leukocyte antigen-matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75%. Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was etfective in combination with MTX for the prevention of acute GVHD. Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors. There was a significant trend toward decreased severity of acute GVHD across all grades (P = .005). Based on the Kaplan-Meier estimate, the probability of grade IMV acute GVHD in the tacrolimus group (56%) was significantly lower than in the CSP group (74%; P = .0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65% vs 81%, respectively; P = .019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8). Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54% versus 50% (P = .46) and 47% versus 42% (P = .58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse. (C) 2000 by The American Society of Hematology.

AB - After the transplantation of unmodified marrow from human leukocyte antigen-matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75%. Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was etfective in combination with MTX for the prevention of acute GVHD. Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors. There was a significant trend toward decreased severity of acute GVHD across all grades (P = .005). Based on the Kaplan-Meier estimate, the probability of grade IMV acute GVHD in the tacrolimus group (56%) was significantly lower than in the CSP group (74%; P = .0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65% vs 81%, respectively; P = .019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8). Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54% versus 50% (P = .46) and 47% versus 42% (P = .58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse. (C) 2000 by The American Society of Hematology.

UR - http://www.scopus.com/inward/record.url?scp=0034665674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034665674&partnerID=8YFLogxK

M3 - Article

C2 - 10979948

AN - SCOPUS:0034665674

VL - 96

SP - 2062

EP - 2068

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -