PMID- 26729448
OWN - NLM
STAT- MEDLINE
DCOM- 20160808
LR  - 20181113
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 173
IP  - 1
DP  - 2016 Apr
TI  - The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in 
      reduced intensity allogeneic stem cell transplantation for lymphoma: a 
      multicentre randomized trial.
PG  - 96-104
LID - 10.1111/bjh.13931 [doi]
AB  - Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical 
      activity in lymphoma. The mTOR inhibitor sirolimus has been used in the 
      prevention and treatment of graft-versus-host disease (GVHD) after allogeneic 
      haematopoietic stem cell transplantation (HSCT). A retrospective study suggested 
      that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT 
      who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate 
      of relapse. We therefore performed a multicentre randomized trial comparing 
      tacrolimus, sirolimus and methotrexate to standard regimens in adult patients 
      undergoing RIC HSCT for lymphoma in order to assess the possible benefit of 
      sirolimus on HSCT outcome. 139 patients were randomized. There was no difference 
      overall in 2-year overall survival, progression-free survival, relapse, 
      non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had 
      a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, 
      P = 0.015), which was more marked for unrelated donor grafts. In conclusion, the 
      addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no 
      increased overall toxicity and a lower risk of acute GVHD, although it does not 
      improve survival; this regimen is an acceptable option for GVHD prevention in RIC 
      HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Armand, Philippe
AU  - Armand P
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Kim, Haesook T
AU  - Kim HT
AD  - Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, 
      MA, USA.
FAU - Sainvil, Marie-Michele
AU  - Sainvil MM
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Lange, Paulina B
AU  - Lange PB
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Giardino, Angela A
AU  - Giardino AA
AD  - Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Bachanova, Veronika
AU  - Bachanova V
AD  - Department of Medical Oncology, University of Minnesota, Minneapolis, MN, USA.
FAU - Devine, Steven M
AU  - Devine SM
AD  - Department of Medicine, The Ohio State University Comprehensive Cancer Center 
      Ohio State University, Columbus, OH, USA.
FAU - Waller, Edmund K
AU  - Waller EK
AD  - Department of Hematology/Oncology, Winship Cancer Institute, Emory University, 
      Atlanta, GA, USA.
FAU - Jagirdar, Neera
AU  - Jagirdar N
AD  - Department of Hematology/Oncology, Winship Cancer Institute, Emory University, 
      Atlanta, GA, USA.
FAU - Herrera, Alex F
AU  - Herrera AF
AD  - City of Hope Cancer Center, Duarte, CA, USA.
FAU - Cutler, Corey
AU  - Cutler C
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Ho, Vincent T
AU  - Ho VT
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Koreth, John
AU  - Koreth J
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Alyea, Edwin P
AU  - Alyea EP
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - McAfee, Steven L
AU  - McAfee SL
AD  - Bone Marrow Transplant Unit, Division of Hematology/Oncology, Massachusetts 
      General Hospital, Boston, MA, USA.
FAU - Soiffer, Robert J
AU  - Soiffer RJ
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Chen, Yi-Bin
AU  - Chen YB
AD  - Bone Marrow Transplant Unit, Division of Hematology/Oncology, Massachusetts 
      General Hospital, Boston, MA, USA.
FAU - Antin, Joseph H
AU  - Antin JH
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00928018
GR  - UL1 TR000114/TR/NCATS NIH HHS/United States
GR  - KL2 TR000113/TR/NCATS NIH HHS/United States
GR  - U19 AI029530/AI/NIAID NIH HHS/United States
GR  - KL2 RR033182/RR/NCRR NIH HHS/United States
GR  - R01 CA183559/CA/NCI NIH HHS/United States
GR  - P01 CA142106/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160105
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Allografts
MH  - Female
MH  - Graft vs Host Disease/*prevention & control
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Lymphoma/*therapy
MH  - Male
MH  - Methotrexate/administration & dosage
MH  - Middle Aged
MH  - Sirolimus/*administration & dosage
MH  - Tacrolimus/administration & dosage
MH  - Transplantation Conditioning/*methods
PMC - PMC4809783
MID - NIHMS746272
OTO - NOTNLM
OT  - GVHD
OT  - clinical trials
OT  - lymphomas
OT  - stem cell transplantation
EDAT- 2016/01/06 06:00
MHDA- 2016/08/09 06:00
PMCR- 2017/04/01
CRDT- 2016/01/06 06:00
PHST- 2015/09/19 00:00 [received]
PHST- 2015/11/18 00:00 [accepted]
PHST- 2016/01/06 06:00 [entrez]
PHST- 2016/01/06 06:00 [pubmed]
PHST- 2016/08/09 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - 10.1111/bjh.13931 [doi]
PST - ppublish
SO  - Br J Haematol. 2016 Apr;173(1):96-104. doi: 10.1111/bjh.13931. Epub 2016 Jan 5.