CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust

Abstract

Aggressive T-cell depletion, in vitro or in vivo, is a prerequisite for survival of haplo-identical stem cell transplantation. The classical T-cell-depleted transplant, immunomagnetically enriched CD34+ cells, is very safe with respect to graft-versus-host reactivity, but associated with very high transplant-related and relapse mortality with an overall probability of survival of only 20%. Protocols for T- and B-cell depletion were therefore developed, reasoning that transplantation of the majority of Natural Killer (NK) cells and the substantial dose of residual T-cells might improve survival, which was, in principle, confirmed. Anecdotal reports of frequent failure to achieve adequate T-cell depletion prompted review of the aggregate data for transplant quality at our center. The first observation is the relative paucity of combined CD3/CD19 depletion processes as PTCy protocols have made inroads, 13 depletions in 8 years. Median T- and B-cell log-depletion were -3.89 and -1.92, respectively; instead of, CD34+ cell recovery was generally high (median 92%), as was NK-cell recovery (median 52%). However, the process failed to yield satisfactory T- and B-cell depletion in two out of 13 preparations, of which one product could be rescued by a second round of depletion, at the expense of CD34+ cell recovery. In our hands, the process is thus insufficiently robust for routine clinical use. Assuming similar observations in other centers, this may explain implementation of alternative protocols, such as TCRαβ/CD19 depletion or transplantation of unmanipulated grafts with subsequent in vivo depletion.

Keywords: CliniMACS; Immunomagnetic depletion; TCRαβ/CD19 depletion; graft failure; graft-versus-host disease; haplo-identical transplantation.

Figure 1

Outcomes of CD3/CD19-depletions: CD34+ cell recovery (A), CD3+ cell depletion (B), number of T-cells per 1 million CD34+ cells (C), CD20+ cell depletion (D) and CD56/16+ cell recovery (E) are depicted. Recovery and depletion are calculated as the total number of post-depletion cells divided by pre-depletion cells, thus accounting for all cell loss during processing and due to quality control sampling. T-cell dose per million CD34+ cells, arguably the most patient-relevant value, is calculated as post-depletion T-cells (total) divided by CD34+ cells (total/10⁶). Each dot represents one depletion process, the bar marking the median (n = 13 depletions).