Effect of nucleated marrow cell dose on
relapse and survival in identical twin bone marrow transplants for
leukemia.
Barrett AJ, Ringden O, Zhang
MJ, Bashey A, Cahn JY, Cairo MS, Gale RP, Gratwohl A, Locatelli F, Martino R,
Schultz KR, Tiberghien P
International Bone Marrow Transplant
Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, WI
53226, USA.
The impact of cell dose (number of nucleated donor cells per
kilogram recipient weight) on transplantation outcome is controversial and may
differ for allogeneic and identical twin (syngeneic) bone marrow transplants. We
studied the association between cell dose and outcome in 100 unmanipulated
identical twin bone marrow transplantations for leukemia, reported to the
International Bone Marrow Transplant Registry between 1985 and 1994, using Cox
proportional hazards regression for multivariate analyses. Cell doses ranged
from 0.3 to 7.4 x 10(8) nucleated cells/kg (median, 3.0 x 10(8)cells/kg). Median
follow-up was 75 months. Five-year cumulative incidences of transplant-related
mortality with high (more than 3 x 10(8) cells/kg) versus low (less than or
equal to 3 x 10(8) cells/kg) cell doses were 2% (95% confidence interval [CI],
0% to 8%) versus 10% (95% CI, 4% to 20%), respectively. Five-year probabilities
of leukemia-free survival were 53% (95% CI, 39% to 67%) and 37% (95% CI, 23% to
52%), respectively. In multivariate analysis, among patients surviving in
remission at least 9 months after transplantation, those receiving high cell
doses were at significantly lower risk for treatment failure (relapse or death)
than those receiving low cell doses (RR, 0.27; 95% CI, 0.12 to 0.6; P =.001).
Lower treatment failure resulted from fewer relapses in the high cell dose group
(RR for relapse, 0.28; 95% CI, 1.2 to 0.66; P =.003). These findings suggest
that outcomes after syngeneic bone marrow transplantation could be improved by
transplanting more than 3 x 10(8) nucleated cells per kilogram. The benefit of
high cell dose on relapse may represent a delayed graft-versus-leukemia
effect.
