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A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation. Haematologica 2014 Oct;99(10):1624-31 PMID: 25085357 PMCID: PMC4181260

Pubmed ID

25085357

Abstract

The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after non-myeloablative (90 mg/m(2) fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: arm 1 - tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2 - tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3 - tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at Day 150, respectively (arm 3 vs. arm 1 (hazard ratio 0.62; P=0.04). Owing to the decreased incidence of acute graft-versus-host disease, systemic steroid use was lower at Day 150 in arm 3 (32% vs. 55% in arm 1 and 49% in arm 2; overall P=0.009 by hazard ratio analysis). The Day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=0.002 by hazard ratio analysis). Non-relapse mortality was comparable in the three arms at two years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between the three arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. (clinicaltrials.gov identifier: 00105001).

Author List

Kornblit B, Maloney DG, Storer BE, Maris MB, Vindeløv L, Hari P, Langston AA, Pulsipher MA, Bethge WA, Chauncey TR, Lange T, Petersen FB, Hübel K, Woolfrey AE, Flowers ME, Storb R, Sandmaier BM

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84907495257   16 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Female
Follow-Up Studies
Graft Rejection
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Incidence
Leukemia
Lymphoma
Male
Middle Aged
Mycophenolic Acid
Recurrence
Sirolimus
Tacrolimus
Transplantation Chimera
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome
Unrelated Donors
Young Adult
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3