PMID- 15172196
OWN - NLM
STAT- MEDLINE
DCOM- 20040727
LR  - 20131121
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 120
IP  - 1
DP  - 2004 Jul
TI  - Bone marrow chimerism and tolerance induced by single-dose cyclophosphamide.
PG  - 102-10
AB  - BACKGROUND: Establishment of hematopoietic chimerism is the most stable strategy 
      for donor-specific tolerance. Safer pretreatment regimens are needed for clinical 
      application. We evaluated the efficacy of a simple protocol using 
      cyclophosphamide (CYP) on induction of chimerism and organ transplant tolerance 
      across major histocompatibility complex (MHC) barriers in the rat. MATERIALS AND 
      METHODS: Bone marrow cells from BN (RT1(n)) donors were infused to LEW (RT1(l)) 
      recipients on day 0 after a single injection of CYP at various doses on day -1. 
      Donor-derived hematopoietic chimerism was evaluated by flowcytometry. The 
      recipients received BN or third party (BUF) heart allografts on day 100. RESULTS: 
      While pretreatment with 200 mg/kg of CYP induced high levels of hematopoietic 
      chimerism, six of eight recipients died of severe graft-versus-host-disease 
      (GVHD). CYP at dose of 150 mg/kg induced 36.5 +/- 24.1% of donor-derived 
      chimerism on day 10, and sustained macrochimerism was seen until day 100 without 
      GVHD. Pretreatment with 100 mg/kg of CYP resulted in only transient chimerism 
      (4.8 +/- 5.2%) which disappeared by day 20. In the recipients with 50 mg/kg of 
      CYP, donor bone marrow cells were rapidly rejected and no chimerism was observed. 
      The recipients with 150 mg/kg of CYP accepted BN heart allografts (>100 days x 
      5), while rejecting BUF allografts by day 12 (n = 4). BN heart allografts were 
      rejected in the recipients with 100 (MST: 57 days, n = 5) and 50 mg/kg (MST: 7 
      days, n = 5) of CYP. CONCLUSIONS: A single dose of CYP can induce hematopoietic 
      chimerism across MHC-barriers. The dose of 150 mg/kg seems to be optimal to 
      induce organ transplant tolerance without developing GVHD.
FAU - Okayama, Junji
AU  - Okayama J
AD  - First Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, 
      Nara 634-8522, Japan.
FAU - Ko, Saiho
AU  - Ko S
FAU - Kanehiro, Hiromichi
AU  - Kanehiro H
FAU - Kanokogi, Hideki
AU  - Kanokogi H
FAU - Hisanaga, Michiyoshi
AU  - Hisanaga M
FAU - Ohashi, Kazuo
AU  - Ohashi K
FAU - Sho, Masayuki
AU  - Sho M
FAU - Nagao, Mitsuo
AU  - Nagao M
FAU - Ikeda, Naoya
AU  - Ikeda N
FAU - Kanamura, Tetsuhiro
AU  - Kanamura T
FAU - Akashi, Satoru
AU  - Akashi S
FAU - Nakajima, Yoshiyuki
AU  - Nakajima Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Immunosuppressive Agents)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/*immunology
MH  - Cyclophosphamide/immunology/*pharmacology
MH  - Heart Transplantation/immunology
MH  - Immunosuppressive Agents/immunology/*pharmacology
MH  - Major Histocompatibility Complex/immunology
MH  - Models, Animal
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Transplantation Chimera/*immunology
MH  - Transplantation Tolerance/*drug effects/immunology
EDAT- 2004/06/03 05:00
MHDA- 2004/07/28 05:00
CRDT- 2004/06/03 05:00
PHST- 2003/09/11 00:00 [received]
PHST- 2004/06/03 05:00 [pubmed]
PHST- 2004/07/28 05:00 [medline]
PHST- 2004/06/03 05:00 [entrez]
AID - S0022480404000290 [pii]
AID - 10.1016/j.jss.2004.01.011 [doi]
PST - ppublish
SO  - J Surg Res. 2004 Jul;120(1):102-10. doi: 10.1016/j.jss.2004.01.011.