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 × 10(10)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 × 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.

Figure 1.

Scatter plot of TNC vs. CD34⁺ cell dose with Spearman coefficient of 0.25 (0.18–0.32).

Figure 2.

Regression analyses of TNC dose. Dichotomized regression analysis of the top three quartiles (collapsed) vs. quartile one, showing increased cumulative risk of chronic GVHD at 1 year with higher TNC dose (HR=0.71, P=0.0063).

Figure 3.

Regression analyses of TNC dose. (A) Dichotomized regression analysis of the first three quartiles (collapsed) vs. quartile four, showing decreased risk of 3-year cumulative relapse with higher TNC dose (HR=0.66, P=0.0012). (B) Dichotomized regression analysis of the first three quartiles (collapsed) vs. quartile four, showing no significant effect of TNC dose on 3-year cumulative incidence of non-relapse mortality (NRM) (P=0.43).

Figure 4.

Dichotomized regression analyses of TNC dose. (A) Dichotomized regression analysis of first three quartiles (collapsed) vs. quartile four, showing improved 3-year progression-free survival (PFS) with higher TNC dose (HR=0.68, P=0.00067). (B) Dichotomized regression analysis of first three quartiles (collapsed) vs. quartile four, showing improved 3-year overall survival (OS) with higher TNC dose (HR=0.69, P=0.0028).