PMID- 29326124
OWN - NLM
STAT- MEDLINE
DCOM- 20190306
LR  - 20211204
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 103
IP  - 3
DP  - 2018 Mar
TI  - Bortezomib-based immunosuppression after reduced-intensity conditioning 
      hematopoietic stem cell transplantation: randomized phase II results.
PG  - 522-530
LID - 10.3324/haematol.2017.176859 [doi]
AB  - Aprior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after 
      human leukocyte antigen (HLA)-mismatched reduced intensity conditioning 
      allogeneic hematopoietic stem cell transplantation documented low acute 
      graft-versus-host disease incidence, with promising overall and progression-free 
      survival. We performed an open-label three-arm 1:1:1 phase II randomized 
      controlled trial comparing grade II-IV acute graft-versus-host disease between 
      conventional tacrolimus/methotrexate (A) versus 
      bortezomib/tacrolimus/methotrexate (B), and versus 
      bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic 
      transplantation recipients lacking HLA-matched related donors. The primary 
      endpoint was grade II-IV acute graft-versus-host disease incidence rate by day 
      +180. One hundred and thirty-eight patients (A 46, B 45, C 47) with a median age 
      of 64 years (range: 24-75), varying malignant diagnoses and disease risk (low 14, 
      intermediate 96, high/very high 28) received 7-8/8 HLA-mismatched (40) or matched 
      unrelated donor (98) grafts. Median follow up in survivors was 30 months (range: 
      14-46). Despite early immune reconstitution differences, day +180 grade II-IV 
      acute graft-versus-host disease rates were similar (A 32.6%, B 31.1%, C 21%; 
      P=0.53 for A vs B, P=0.16 for A vs C). The 2-year non-relapse mortality incidence 
      was similar (A 14%, B 16%, C 6.4%; P=0.62), as were relapse (A 32%, B 32%, C 38%; 
      P=0.74), chronic graft-versus-host disease (A 59%, B 60% C 55%; P=0.66), 
      progression-free survival (A 54%, B 52%, C 55%; P=0.95), and overall survival (A 
      61%, B 62%, C 62%; P=0.98). Overall, the bortezomib-based regimens evaluated did 
      not improve outcomes compared with tacrolimus/methotrexate therapy. 
      clinicaltrials.gov Identifier: 01754389.
CI  - Copyright(c) 2018 Ferrata Storti Foundation.
FAU - Koreth, John
AU  - Koreth J
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA john_koreth@dfci.harvard.edu.
FAU - Kim, Haesook T
AU  - Kim HT
AD  - Department of Biostatistics and Computational Biology, Dana-Farber Cancer 
      Institute and Harvard School of Public Health, Boston, MA.
FAU - Lange, Paulina B
AU  - Lange PB
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Poryanda, Samuel J
AU  - Poryanda SJ
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Reynolds, Carol G
AU  - Reynolds CG
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Rai, Sharmila Chamling
AU  - Rai SC
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Armand, Philippe
AU  - Armand P
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Cutler, Corey S
AU  - Cutler CS
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Ho, Vincent T
AU  - Ho VT
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Glotzbecker, Brett
AU  - Glotzbecker B
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Yusuf, Rushdia
AU  - Yusuf R
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Nikiforow, Sarah
AU  - Nikiforow S
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Chen, Yi-Bin
AU  - Chen YB
AD  - Massachusetts General Hospital Cancer Center, Boston, MA.
FAU - Dey, Bimalangshu
AU  - Dey B
AD  - Massachusetts General Hospital Cancer Center, Boston, MA.
FAU - McMasters, Malgorzata
AU  - McMasters M
AD  - Beth Israel Deaconess Hospital Cancer Center, Boston, MA.
FAU - Ritz, Jerome
AU  - Ritz J
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Blazar, Bruce R
AU  - Blazar BR
AD  - University of Minnesota Masonic Cancer Center and Department of Pediatrics, 
      Division of Blood and Marrow Transplantation, Minneapolis, MN, USA.
FAU - Soiffer, Robert J
AU  - Soiffer RJ
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Antin, Joseph H
AU  - Antin JH
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
FAU - Alyea, Edwin P 3rd
AU  - Alyea EP 3rd
AD  - Division of Hematologic Malignancies, Dana-Farber Cancer Institute and Harvard 
      Medical School, Boston, MA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01754389
GR  - P01 CA142106/CA/NCI NIH HHS/United States
GR  - R01 CA183559/CA/NCI NIH HHS/United States
GR  - R01 CA183560/CA/NCI NIH HHS/United States
GR  - R01 HL118979/HL/NHLBI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180111
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 69G8BD63PP (Bortezomib)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
CIN - Haematologica. 2018 Mar;103(3):377-379. PMID: 29491127
MH  - Adult
MH  - Aged
MH  - Allografts
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Bortezomib/*therapeutic use
MH  - Female
MH  - Graft vs Host Disease/etiology
MH  - Hematologic Diseases/mortality/therapy
MH  - Hematopoietic Stem Cell Transplantation/adverse effects/*methods
MH  - Humans
MH  - Immunosuppression Therapy/*methods
MH  - Male
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Survival Analysis
MH  - Tacrolimus/therapeutic use
MH  - Transplantation Conditioning/*methods
MH  - Young Adult
PMC - PMC5830392
EDAT- 2018/01/13 06:00
MHDA- 2019/03/07 06:00
PMCR- 2018/03/01
CRDT- 2018/01/13 06:00
PHST- 2017/07/18 00:00 [received]
PHST- 2018/01/10 00:00 [accepted]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2019/03/07 06:00 [medline]
PHST- 2018/01/13 06:00 [entrez]
PHST- 2018/03/01 00:00 [pmc-release]
AID - haematol.2017.176859 [pii]
AID - 1030522 [pii]
AID - 10.3324/haematol.2017.176859 [doi]
PST - ppublish
SO  - Haematologica. 2018 Mar;103(3):522-530. doi: 10.3324/haematol.2017.176859. Epub 
      2018 Jan 11.