PMID- 12023614
OWN - NLM
STAT- MEDLINE
DCOM- 20020611
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 73
IP  - 9
DP  - 2002 May 15
TI  - Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney 
      and hematopoietic progenitor transplantation.
PG  - 1386-91
AB  - BACKGROUND: Rodents and dogs conditioned with total-lymphoid irradiation (TLI), 
      with or without antithymocyte globulin (ATG), have been shown to develop mixed 
      chimerism and immune tolerance without graft-versus-host disease (GVHD) after the 
      infusion of major histocompatability complex (MHC)-mismatched donor bone marrow 
      cells given alone or in combination with an organ allograft. METHODS: Four human 
      leukocyte antigen (HLA)-mismatched recipients of living donor kidney transplants 
      were conditioned with TLI and ATG posttransplantation and infused with 
      cyropreserved donor granulocyte colony-stimulating factor (G-CSF) "mobilized" 
      hematopoietic progenitor (CD34+) cells (3-5x10(6) cells/kg) thereafter. 
      Maintenance prednisone and cyclosporine dosages were tapered, and recipients were 
      monitored for chimerism, GVHD, graft function, T-cell subsets in the blood, and 
      antidonor reactivity in the mixed leukocyte reaction (MLR). RESULTS: Three of the 
      four patients achieved multilineage macrochimerism, with up to 16% of donor-type 
      cells among blood mononuclear cells without evidence of GVHD. Prolonged depletion 
      of CD4+ T cells was observed in all four patients. Rejection episodes were not 
      observed in the three macrochimeric recipients, and immunosuppressive drugs were 
      withdrawn in the first patient by 12 months. Prednisone was withdrawn from a 
      second patient at 9 months, and cyclosporine was tapered thereafter. CONCLUSIONS: 
      Multilineage macrochimerism can be achieved without GVHD in HLA-mismatched 
      recipients of combined kidney and hematopoietic progenitor transplants. 
      Conditioning of the host with posttransplant TLI and ATG was nonmyeloablative and 
      was not associated with severe infections. Recipients continue to be studied for 
      the development of immune tolerance.
FAU - Millan, Maria T
AU  - Millan MT
AD  - Department of Surgery, Division of Transplantation, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
FAU - Shizuru, Judith A
AU  - Shizuru JA
FAU - Hoffmann, Petra
AU  - Hoffmann P
FAU - Dejbakhsh-Jones, Sussan
AU  - Dejbakhsh-Jones S
FAU - Scandling, John D
AU  - Scandling JD
FAU - Grumet, F Carl
AU  - Grumet FC
FAU - Tan, Jane C
AU  - Tan JC
FAU - Salvatierra, Oscar
AU  - Salvatierra O
FAU - Hoppe, Richard T
AU  - Hoppe RT
FAU - Strober, Samuel
AU  - Strober S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
SB  - IM
MH  - Adult
MH  - *Blood Group Incompatibility
MH  - Drug Administration Schedule
MH  - Female
MH  - HLA Antigens/*analysis
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/therapeutic use
MH  - Kidney Transplantation/*immunology
MH  - Leukocyte Count
MH  - Lymphatic Irradiation
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocyte Subsets/pathology
MH  - *Transplantation Chimera
MH  - Transplantation Immunology/*genetics
MH  - Treatment Outcome
EDAT- 2002/05/23 10:00
MHDA- 2002/06/12 10:01
CRDT- 2002/05/23 10:00
PHST- 2002/05/23 10:00 [pubmed]
PHST- 2002/06/12 10:01 [medline]
PHST- 2002/05/23 10:00 [entrez]
AID - 10.1097/00007890-200205150-00005 [doi]
PST - ppublish
SO  - Transplantation. 2002 May 15;73(9):1386-91. doi: 
      10.1097/00007890-200205150-00005.