PMID- 22262128
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20161125
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 93
IP  - 6
DP  - 2012 Mar 27
TI  - Durability of antibody removal following proteasome inhibitor-based therapy.
PG  - 572-7
LID - 10.1097/TP.0b013e31824612df [doi]
AB  - BACKGROUND: Evidence of the short-term effect of bortezomib on donor-specific 
      human leukocyte antigen (HLA) antibody (DSA) removal capacity has emerged. 
      However, no published data characterize the durability of DSA response. Here, we 
      report the long-term DSA response results on renal transplant patients treated 
      with bortezomib. METHODS: In this single-center study, 26 living-donor renal 
      transplant patients with a positive level of de novo DSA were preemptively 
      treated with bortezomib (1.3 mg/m x 4 doses). A total of 15 patients received 
      bortezomib as part of a combination regimen; 11 received bortezomib alone. Weekly 
      serial measurements of HLA antibody were noted before, during, and after 
      treatment using single-antigen beads. RESULTS: At a median follow-up of 25.8 
      months posttreatment, allograft function remained good in each of the patients. 
      Following treatment, 96% of the patients achieved at least a partial response. 
      Eighteen patients (69%) experienced a complete response followed by a period of 
      DSA remission. Ten patients had DSA relapse after remission, at a median of 3.8 
      months. The remaining eight patients are still in remission at 14 months 
      posttreatment (median). Patients with remission enjoyed better allograft 
      functional stability than those who relapsed (P=0.023). After bortezomib therapy, 
      the addition of a calcineurin inhibitor or mycophenolate mofetil was predictive 
      for maintaining a DSA remission (hazard ratio 0.09, 95% confidence interval 
      0.01-0.76). CONCLUSIONS: Bortezomib therapy consistently provides reduction in 
      DSA and in many a DSA remission may occur. However, sustaining remission is 
      likely necessary to improve allograft stability.
FAU - Everly, Matthew J
AU  - Everly MJ
AD  - One Lambda Inc., Research 2 Division, Los Angeles, CA 90064, USA. 
      meverly@onelambda.com
FAU - Terasaki, Paul I
AU  - Terasaki PI
FAU - Trivedi, Hargovind L
AU  - Trivedi HL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Boronic Acids)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoantibodies)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Adult
MH  - Boronic Acids/*therapeutic use
MH  - Bortezomib
MH  - Calcineurin Inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/immunology/*prevention & control
MH  - Graft Survival/immunology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Isoantibodies/*blood
MH  - Kidney Transplantation/*immunology
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/analogs & derivatives/therapeutic use
MH  - Prognosis
MH  - *Proteasome Inhibitors
MH  - Pyrazines/*therapeutic use
MH  - Retrospective Studies
MH  - *Tissue Donors
MH  - Transplantation, Homologous
EDAT- 2012/01/21 06:00
MHDA- 2012/05/02 06:00
CRDT- 2012/01/21 06:00
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
AID - 10.1097/TP.0b013e31824612df [doi]
PST - ppublish
SO  - Transplantation. 2012 Mar 27;93(6):572-7. doi: 10.1097/TP.0b013e31824612df.