Selective TCRαβ+ and CD45RA+ T-cell depletion of hematopoietic stem cell graft: An analysis on factors that affect depletion performance

Selective depletion of TCRαβ+ and CD45RA+ subsets of apheresed hematopoietic progenitor cells, HPC(A), enables haploidentical hematopoietic stem cell transplant (haplo-HSCT) by circumventing risks of graft-versus-host disease. Here, we analyze our institution's large series of <i>ex vivo</i> T-cell depletion processes to review procedure performance and explore factors that affect depletion efficiency and graft composition. Over 6 years, 91 haploidentical donors underwent peripheral blood CD34+ stem cell mobilization with granulocyte-colony stimulating factor, with 12 (13%) receiving additional pre-emptive plerixafor. HPC(A) was split into two fractions for TCRαβ and CD45RA depletion with the CliniMACS PLUS device. TCRαβ depletion resulted in a median 4.3 (interquartile range, 4.1-4.5) log reduction, with CD34 recovery at 98% (94%-103%) and TCRγδ+ cell recovery at 89% (74%-98%). CD45RA depletion resulted in a median 4.8 (4.3-5.2) log reduction, with CD3+/CD45RO+ cell recovery at 41% (34%-47%) and CD34 recovery at 58% (51%-68%). TCRαβ depletion efficiency was maintained even when total nucleated cell counts exceeded the maximal specified number, provided the target fraction was within capacity of the depletion kit. Platelet contamination did not affect depletion efficacy or CD34 recovery. Age increases the proportion of CD45RO+ memory cells and TCRαβ subset in HPC(A), while plerixafor increases the latter. Although statistically significant correlation exists between pre-depletion cell composition and depletion performance for some cell subsets, the post-depletion product still met pre-specified threshold without being affected to a clinically relevant extent, over a wide range of input cell numbers. Such robustness of the depletion systems is critical for successful performance of haplo-HSCT.