Limited efficacy and unacceptable toxicity of cyclophosphamide for the induction of mixed chimerism and renal allograft tolerance in cynomolgus monkeys

Hiroshi Sogawa, Svjetlan Boskovic, Ognjenka Nadazdin, Greg Abrahamian, Robert B. Colvin, David H. Sachs, A. Benedict Cosimi, Tatsuo Kawai

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

To induce mixed chimerism and renal allograft tolerance in cynomolgus monkeys, cyclophosphamide (CP) and total body irradiation (TBI) were compared as part of a nonmyeloablative conditioning regimen. CP induced dose-dependent neutropenia and lymphopenia, but hematopoietic recovery was more rapid than that observed in the TBI group. Absolute B cell counts after CP were significantly higher (P<0.01) than those in the TBI group. With CP, a total dose of 200 mg/kg with CD154 blockade regularly induced multilineage chimerism. Nevertheless, the recipients failed to achieve long-term survival because of rejection (3 of 5), posttransplantation B cell lymphoma (1 of 5), and toxicities of CP (1 of 5). As previously reported, 3 Gy of TBI with either splenectomy or CD154 blockade induced mixed chimerism and renal allograft tolerance, with significantly less morbidity and mortality than that produced by CP. Thus, TBI is more effective and less toxic than CP as part of a nonmyeloablative regimen for the induction of mixed chimerism and renal allograft tolerance in cynomolgus monkeys.

Original languageEnglish (US)
Pages (from-to)615-619
Number of pages5
JournalTransplantation
Volume86
Issue number4
DOIs
StatePublished - Aug 27 2008

Keywords

  • Cyclophosphamide
  • Kidney transplantation
  • Mixed chimerism
  • Monkeys
  • Tolerance

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Limited efficacy and unacceptable toxicity of cyclophosphamide for the induction of mixed chimerism and renal allograft tolerance in cynomolgus monkeys'. Together they form a unique fingerprint.

Cite this