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Author Notes:

Corresponding author: Philippe Armand, MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston MA 02215, 617-632-2305 (ph); 617-632-4422 (fax), parmand@partners.org

P.A. designed the research, analysed the data and wrote the paper.

H.T.K. designed the research, analysed the data and edited the paper.

M.M.S. collected data and edited the paper.

P.B.L. collected data and edited the paper.

A.A.G. analysed data and edited the paper.

V.B. designed the research, collected data and edited the paper.

S.M.D. designed the research, collected data and edited the paper.

E.K.W. designed the research, collected data and edited the paper.

N.J., A.H., C.C., V.T.H., J.k., E.P.A, S.L.M, collected data and edited the paper.

R.J.S., Y.-B.C., J.H.A. designed the research, collected data and edited the paper.

We are also indebted to the nursing and research staff who were involved in this study, and to all of the participants and their families.

The authors have no relevant conflicts of interest to disclose.

The interim analysis of this study was presented at an oral session of the American Society of Hematology meeting in December 2013 in New Orleans, LA.

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Research Funding:

P.A. was supported by an ASH Scholar Award, an ASCO Career Development Award, an ASBMT/Genentech Young Investigator Award, and a Dunkin Donuts Rising Star award for this work.

This work was also supported by NIAID U19 AI 29530, NCI P01 CA142106, and the Jock and Bunny Adams Research and Education Endowment.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • clinical trials
  • lymphomas
  • stem cell transplantation
  • GVHD
  • PHASE-II TRIAL
  • LOW-DOSE METHOTREXATE
  • UNRELATED DONOR TRANSPLANTATION
  • SINGLE-AGENT TEMSIROLIMUS
  • GVHD PROPHYLAXIS
  • CLINICAL-TRIALS
  • TACROLIMUS
  • COMBINATION
  • BLOOD
  • EVEROLIMUS

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

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Journal Title:

British Journal of Haematology

Volume:

Volume 173, Number 1

Publisher:

, Pages 96-104

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Inhibition of the mechanistic target of rapamycin (serine/threonine kinase) (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-i.v. acute GVHD (9% versus 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).

Copyright information:

© 2016 John Wiley & Sons Ltd

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