A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation.

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).

• Authors: Brian Kornblit, David G Maloney, Barry E Storer, Michael B Maris, Lars Vindeløv, Parameswaran Hari, Amelia A Langston, Michael A Pulsipher, Wolfgang A Bethge, Thomas R Chauncey, Thoralf Lange, Finn B Petersen, Kai Hübel, Ann E Woolfrey, Mary E D Flowers, Rainer Storb, Brenda M Sandmaier
• Journal: Haematologica (Haematologica) Vol. 99 Issue 10 Pg. 1624-31 (Oct 2014) ISSN: 1592-8721 [Electronic] Italy
• PMID: 25085357 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Mycophenolic Acid
• Sirolimus
• Tacrolimus

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Female
• Follow-Up Studies
• Graft Rejection
• Graft vs Host Disease (diagnosis, etiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Incidence
• Leukemia (diagnosis, mortality, therapy)
• Lymphoma (diagnosis, mortality, therapy)
• Male
• Middle Aged
• Mycophenolic Acid (administration & dosage, analogs & derivatives)
• Recurrence
• Sirolimus (administration & dosage)
• Tacrolimus (administration & dosage)
• Transplantation Chimera
• Transplantation Conditioning
• Transplantation, Homologous
• Treatment Outcome
• Unrelated Donors
• Young Adult