title: 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.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kornblit
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Colorado Blood Cancer Institute, Denver, CO, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.affiliation: Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Vindeløv
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.affiliation: Emory University, Atlanta, GA, USA.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.affiliation: Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: University of Tübingen Medical Center, Germany.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
authors.affiliation: VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.affiliation: University of Leipzig, Germany.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.affiliation: LDS Hospital, Salt Lake City, UT, USA.
authors.forename: Finn B
authors.initials: FB
authors.lastname: Petersen
authors.affiliation: University of Cologne, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Hübel
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, USA bsandmai@fhcrc.org.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D008223:Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D012008:Recurrence; D020123:Sirolimus / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus
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