Impact of CD3/T Regs Ratio in Donor Graft On Survival Rates in Allogeneic Peripheral Blood Stem Cell Transplantation

The therapeutic efficacy of allogeneic stem cell transplantation (alloSCT) for hematological malignancies relies largely on the graft versus leukemia (GvL) effect exerted by the donor CD3 cells, but an uncontrolled graft-versus-host-disease (GvHD) bears a risk of complications. On the other hand, T regs cells (CD4+CD25^high Foxp3+) are believed to maintain tolerance and to inhibit GvHD after alloSCT; also, the Foxp3 gene encodes a transcription factor that is a key for thymic development, so T regs cells could preserve an optimal microenviroment for the reconstitution of functional immunity after alloSCT. Moreover, when looking at post allotransplant patients' outcomes, while it is largely known the impact of acute GVHD (triggered by CD3 donor T cells) on survival, there is no evidence that donor graft CD3/T regs ratio may determine an effect in terms of OS, NRM and relapse free survival rates so far.

In this study we analyzed the graft CD3+/Tregs ratio (gCD3/Tregs R) and determined its impact on acute GVHD (aGVHD), immunological recovery and survival rates (OS, NRM and Relapse) after myeloablative alloPBSCT. We analyzed 74 consecutive patients transplanted with unmanipulated peripheral blood stem cells from an HLA identical related donor (n=48) or an HLA identical unrelated donor (n=26); diagnoses were acute myeloid leukaemia (n=62), acute lymphoblastic leukaemia (n=13). The median CD3+ and Tregs dose administered was 238 (range (r): 67–550) and 12,5×106̂/Kg (r: 2–21), respectively; the median gCD3/Tregs R was 19 (r: 8–250). Patients were subdivided into a high gCD3/Tregs R (>=36) group (HR group n= 30) and a low gCD3/Tregs R (<36) (LR group n=44).

The incidence of aGVHD (grade II-IV) in the low gCD3/Tregs R (LR) group was lower than in the high gCD3/Tregs R (HR) group (4/30 or 13% vs 36/44 or 82%, p<.001). The OS, NRM and relapse rate at 3 years was 54,29 and 34%, respectively. Comparing LR with HR group a statistically significant difference is demonstrated for OS and NRM rates (65 vs 31%,p<.004; 3 vs 71%, p<.001), respectively, but not for the R one (35 vs 30%, p=ns). Comparing aGVHD+ with aGVHD- group OS, NRM and relapse were always statistically significant different (39 vs 65%,p<.005; 61 vs 7%,p<.001; 9 vs 53%,p<.002).

Taken together, our data may suggest that Tregs content is able to mediate protective effects against aGVHD, while preserving GvL effects as demonstrated by relapse rate comparison between H and LR groups. However, larger studies are needed to understand the real contribution of gCD3/Tregs R on survival rates.

No relevant conflicts of interest to declare.