The Impact Of Thymoglobulin Prior To Pediatric Unrelated Umbilical Cord Blood Transplantation On Immune-Reconstitution and Clinical Outcome

In vivo T-cell-depletion generated by the use of Thymoglobulin (ATG) within the conditioning regimen might contribute to the delayed immune-reconstitution observed after unrelated umbilical cord blood transplantation (UCBT). We studied the impact of early, late and no ATG on immune reconstitution and clinical outcome.

127 Children receiving an unrelated UCBT in London or Utrecht between 2006 and 2011 were included and divided in 3 groups: late ATG (day -5 to 0, n=48), early ATG (day -9 to -5, n= 33) and no ATG(n=46). The no ATG group received MMF and CsA as GVHD prophylaxis, while the ATG groups both received CSA and prednison as prohylaxis, Endpoints studied were survival, early and late immune-recovery, infections and GvHD. Subset analysis CD3+, CD4+ and CD4+naïve, B and NK cell numbers were prospectively measured during post-transplant follow-up at 1, 2, 3, 6 and 12 months post-UCBT.

The probability of survival was not significantly different between the groups: 71% +/- 8% (no ATG), 68% +/- 9% (early ATG) and 61% +/- 7% (late ATG). There were no significant differences in engraftment and primary or secondary graft failure. Immune reconstitution as defined by CD3+, CD4+ and CD4+ naïve T-cell counts were significantly higher (p<0.001) in the no ATG group at 1, 2, 3, 6, and 12 months post-UCBT with a log more T cells than in the ATG groups. The median CD3+ T-cell count in the no ATG group at 1, 2, 3, 6 and 12 months post UCBT was 340 x10e6/L, 720 x 10e6/L, 535 x 10e6/L, 940 ± 194 x 10e6/L, and 1860 x 10e6/L respectively. In the no ATG group significantly less viral reactivations (p=0.021) were noted. A higher probability (p<0,001) of severe acute GvHD (31%+/-9%) was found in the no ATG group compared to 18% +/- 9% for the early ATG and 5% +/-4% for the late ATGgroup. This was not associated with a higher probability of chronic GvHD or non-infectious lung injury in the no ATG group.

Cord blood transplantation without Thymoglobulin (ATG), in the context of MMF and CsA post-transplant prophylaxis, is associated with higher GVHD risk but with a surprisingly good immune reconstitution and with an engraftment and survival similar to the groups with ATG. The findings of improved immune-reconstitution, associated with lower viral reactivations, albeit at the cost of increased rates of acute GvHD (but not chronic GvHD), suggest that omitting ATG in cord blood transplantation may be important to prevent viral reactivations, especially in those at high risk for these.

No relevant conflicts of interest to declare.