Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation.

Abstract:

Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies have focused primarily on CD34+ cell dose and report conflicting results, especially in relation to survival endpoints. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34+ cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematological malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000-2010. By multivariable analysis, we found higher total nucleated cell dose (top quartile; ≥ 10.8 x 1010 cells) was associated with improved overall survival (HR 0.69 [0.54-0.88], p=0.0028) and progression free survival (HR 0.68 [0.54-0.85], p=0.0006). Higher total nucleated cell dose was independently associated with decreased relapse (HR 0.66 [0.51-0.85], p=0.0012) and increased incidence of chronic graft-versus-host disease (HR 1.4 [1.12-1.77], p=0.0032). In contrast, higher doses of CD34+ cells (top quartile; ≥ 10.9 x 10^6/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34+ cell dose.