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 focused primarily on CD34+ cell dose and reported conflicting results, especially in relation to survival end-points. 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 hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that 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 106/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.