AFFECTING GRAFT SURVIVAL--DONOR BONE MARROW INFUSION

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the applicant's abstract) Drawbacks of organ
transplantation include the continuous requirement for immunosuppressive
drugs and the occurrence of rejection episodes that, acutely or over time,
contribute to the loss and/or decrease in the function of the allograft. In
addition, the continuous requirement for immunosuppression is responsible
for an increased incidence of infections and malignancies in long term
transplant recipients. The investigators' central hypothesis is that it is
possible to induce donor specific unresponsiveness in recipients of
allografts by high-dose peripheral infusion of donor bone marrow cells
(DBMC), without radiation conditioning of the recipients. In the absence of
cytoablation, variables such as dose and timing of the DBMC infusions may
constitute critical factors that affect graft survival.

The investigators have strong preliminary evidence indicating that: 1)
Human vertebral body bone marrow can provide a significantly higher dose of
hematopoietic precursors compared to bone marrow from other sources, or
peripheral blood. 2) Two or more DBMC infusions were safe as indicated by
improved patient survival. 3) Two or more DBMC infusions resulted in
improved liver allograft survival. 4) The investigators do not have any
evidence that peripheral microchimerism is responsible for the improved
results in the multiple DBMC infusion groups.

Based on preliminary results, the investigators propose a prospective
randomized clinical trial to determine the effect of two high-dose DMBC
infusions on the incidence of rejection episodes and on the ability to
withdraw immunosuppression in recipients of liver allografts.

Even though it is not the investigators' central hypothesis that peripheral
microchimerism is the determining factor in tolerance induction, they will
continue to characterize by flow cytometry and flow-PCR the cellular
composition of chimerism that follows DBMC infusions in recipients of liver
allografts, and will retrospectively determine whether a correlation between
the (quantitative and/or qualitative) characteristics of peripheral
chimerism and post-transplant course (rejection and requirements for
immunosuppression) exists. The development of strategies to improve long
term allograft survival and/or the potential for progressive lowering and
even discontinuation of immunosuppressive therapy would represent a
substantial benefit to the patients and would also decrease the cost of
post-transplant patient care.
StatusFinished
Effective start/end date9/9/967/31/01

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases

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