Background. To date, several single- and multicenter clinical trials have a
ttempted to induce specific immunological unresponsiveness using donor bone
marrow cell infusions to augment solid organ transplantation, but the outc
omes have not been definitive.
Methods. Between September 1994 and May 1998, 63 cadaver (CAD) renal transp
lant recipients of either one or two postoperative donor bone marrow cell (
DBMC) infusions were prospectively compared with 219 non-infused controls g
iven equivalent immunosuppression. There was at least a 1 HLA DR antigen ma
tch present between donors and recipients. The immunosuppressive regimen in
cluded a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mof
etil, and methylprednisolone maintenance. A total 7.01x10(8+/-)11.9x10(8) (
SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=
42) or one half of that dose on day 4 (n=21) postoperatively, Clinical foll
ow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also
performed of humoral immunity and quantitative cellular chimerism,
Results, There is clear-cut equivalence in immunosuppressive dosaging and i
n the other major demographic variables in both groups. However, only 2/63
DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed
chronic rejection in the controls (P=<0.01). In both groups, mortality was
not associated with rejection, The actuarial graft survival at 6.3 years in
the CAD DBMC group was 84.3% compared with 72.2% in the control group (not
statistically significant). However, if death with a functioning graft was
excluded, graft survival was 94.1% in the DBMC group and 79.8% in the cont
rols (P=0.039). Forty patients in the control group continue to have deteri
orating renal function (increasing serum creatinine concentrations to 2 mg/
dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the
DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold
in yearly sequential measurements between 1 and 4 years postoperatively av
eraging 1.3+/-0.36% (SE) most recently. This has not occurred in the contro
ls.
Conclusions. There now appears to be more solid long-term evidence, in kidn
ey transplant recipients prospectively receiving DBMC infusions, of an impr
ovement in long-term graft survival, and of the degree of chimerism positiv
ely correlating with the absence of graft loss.