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T cell depletion (TCD) by negative or positive selection reduces graft-vs-host disease and its complications while maintaining relapse free survival in appropriately selected patients. Differences in acute GVHD incidence of sibling donor transplants using 3 TCD methods stimulated review of graft content. Graft source (bone marrow [BM] or peripheral blood stem cells [PBSC]) and TCD method determine cell composition, impacting outcome and survival. As a center historically committed to TCD, we reviewed 531 TCD grafts processed in 2000-2011 using 3 TCD methods for BM or PBSC. Pre and postprocessing cell composition, log10 TCD, and % CD34+ recovery were compared. BM, negatively selected by soybean lectin agglutination and sheep RBC rosetting (SBA-E-) was used in 76 patients; PBSC, positively selected for CD34+ cells by the Isolex followed by RBC rosetting (IsoE-) for 361 patients, or by the CliniMACS (Clini), for 94 patients. The table shows preprocessing cell doses and phenotypic profile were significantly different between pre BM and pre PBSC for TNC, CD3+T cells, T cell subsets, NK cells and CD34+ (p-values <0.001, Wilcoxon rank-sum test). BM T cells had a 1:1 ratio of CD4:CD8 while PBSC had a 1:2 ratio. The table shows post TCD T cell doses were significantly higher in BM than in PBSC grafts. In TCD BM, the median log 10 depletion of CD3 + T cells (2.65) was significantly different from IsoE log10 TCD (5.22). Clini log 10 TCD (4.92) was similar to IsoE. Strikingly, while preprocessed BM had fewer NK CD56/16+ than PBSC (3.86E+06 vs. 3.59E+07), the negative selection of BM left more NK cells in the TCD graft, resulting in significantly higher NK cell dose (6.73E+05) than after CD34+ positive selection by Iso E- (2.25E+03) or Clini (6.98E+02). IsoE- had significantly (p<0.001) higher CD34 doses (7.31E+06 /kg) and greater recovery (85.0%) of CD34+ cells; than SBA-E- (1.86E+06 /kg, 33.3% recovery). Clini selection resulted in similar CD34 cell doses and recovery to the IsoE-. (1.05E+07/kg, 116.74 % recovery). Number and types of CD3+ T cells, T subpopulations, NK, and CD34+ in TCD grafts act in concert with donor and host parameters to effect final transplant outcome. Characterization of cells in preprocessed grafts and retained by TCD methods can lead to better graft engineering and optimization of the cellular content of the final T depleted product.
Table Median Cell Dose/kg Pre and Post TCD
Cells
| TNC
| CD34
| CD3
| CD4
| CD8
| TCR gd | CD56/16
|
Pre BM
| 3.81E+08
| 5.87E+06
| 2.69E+07
| 1.32E+07
| 1.27E+07
| 1.26E+06
| 3.86E+06
|
Pre PBSC
| 1.19E+09
| 8.72E+06
| 2.38E+08
| 1.37E+08
| 2.59E+08
| 9.71E+06
| 3.59E+07
|
SBA-E-
| 2.84E+07
| 1.86E+06
| 6.07E+04
| 8.30E+03
| 4.04E+04
| 1.20E+04
| 6.73E+05
|
Iso E-
| 7.63E+06
| 7.31E+06
| 1.58E+03
| 3.88E+02
| 7.78E+02
| <1.00E+02
| 2.25E+03
|
Clini
| 8.53E+06
| 1.05E+07
| 3.56E+03
| 2.06E+03
| 1.49E+03
| <1.00E+02
| 6.98E+02
|