PMID- 25095503
OWN - NLM
STAT- MEDLINE
DCOM- 20140909
LR  - 20211021
IS  - 0890-9016 (Print)
IS  - 0890-9016 (Linking)
DP  - 2013
TI  - HLA identical non-chimeric and HLA disparate chimeric renal transplant tolerance.
PG  - 145-56
AB  - In this chapter, we describe studies on non-chimeric human leukocyte antigen 
      (HLA) identical tolerance and chimeric HLA disparate tolerance brought about by 
      infusions of hematopoietic stem cells from the renal donor (DHSC). In our HLA 
      identical series, 4 DHSC infusions were administered during the first 9 months 
      posttransplant in a highly immunoregulatory environment using alemtuzumab 
      induction and rapid conversion from early tacrolimus to mycophenolate and 
      sirolimus. This resulted in the generation of recipient T regulatory cells 
      accompanied by genomic indicators, but only transient chimerism. Seven of the 
      first 12 recipients have been immunosuppression-free between 1 1/2 - 4 years with 
      transplant biopsies free of rejection one year after immunosuppression 
      withdrawal. The HLAdisparate group was treated by non-myeloablative conditioning 
      consisting of: 200cGy whole body irradiation; fludarabine; cyclophosphamide; and, 
      perioperative infusion of a product termed FCRx that contained DHSC, T cells, and 
      a unique fraction of bone marrow derived CD8+TCR-alphabeta-negative cells. Five 
      of the first 8 subjects became 100% chimeric in the peripheral blood and have 
      been immunosuppression-free for 2 to 4 years without graft-versus-host-disease 
      and with normal function and transplant biopsies. An additional 12 recipients 
      with shorter follow-up have had similar courses. Those with non-durable chimerism 
      have not been able to have immunosuppression withdrawn but maintain normal renal 
      transplant function. We conclude that non-HLA disparities in renal transplants 
      between HLA identical pairs may not need durable chimerism to induce tolerance 
      provided by DHSC and temporary immunosuppression supporting the development of 
      regulatory T cells. However, more intense conditioning and infusion of FCRx 
      leading to durable chimerism in the absence of graft versus host disease is 
      necessary to induce tolerance in HLA disparate pairs.
FAU - Leventhal, Joseph R
AU  - Leventhal JR
FAU - Mathew, James M
AU  - Mathew JM
FAU - Ildstad, Suzanne
AU  - Ildstad S
FAU - Salomon, Daniel R
AU  - Salomon DR
FAU - Kurian, Sunil M
AU  - Kurian SM
FAU - Suthanthiran, Manikkam
AU  - Suthanthiran M
FAU - Tambur, Anat
AU  - Tambur A
FAU - Friedewald, John
AU  - Friedewald J
FAU - Gallon, Lorenzo
AU  - Gallon L
FAU - Charette, Jane
AU  - Charette J
FAU - Levitsky, Josh
AU  - Levitsky J
FAU - Kanwar, Yashpal
AU  - Kanwar Y
FAU - Abecassis, Michael
AU  - Abecassis M
FAU - Miller, Joshua
AU  - Miller J
LA  - eng
GR  - R01 DK025243/DK/NIDDK NIH HHS/United States
GR  - R01-25243/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Clin Transpl
JT  - Clinical transplants
JID - 8812419
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - Follow-Up Studies
MH  - Genomics
MH  - Graft Rejection/*immunology/prevention & control
MH  - HLA Antigens/genetics/*immunology
MH  - Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Immunophenotyping
MH  - *Kidney Transplantation
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Tissue Donors
MH  - Transplantation Chimera/*immunology
MH  - Transplantation Tolerance/*immunology
EDAT- 2013/01/01 00:00
MHDA- 2014/09/10 06:00
CRDT- 2014/08/07 06:00
PHST- 2014/08/07 06:00 [entrez]
PHST- 2013/01/01 00:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
PST - ppublish
SO  - Clin Transpl. 2013:145-56.