The Study on Influence of T Cell Ratios Between Grafts to Recipients on Gvhd in HLA- Haploidentical Allogeneic Peripheral Blood Stem Cells Transplantation

Objective To study the influence of T cell ratios between grafts to recipients on GVHD in HLA- haploidentical allogeneic peripheral blood stem cells transplantation ( PBSCT ).

Methods:

1. Animal experiment: We set up rat allo-BMT model. Male SD rats were transplanted with female Wistar rats.Recipient rats of experiment group were transplanted with the CD3⁺ T cells of female Wistar rats at different graft-receptor T cell ratios, 1:1 (group A1), 2:1 ( group A2), 4:1 ( group A3) respectively. Control group (group B) were infused with grafts consisting of 3×10⁷ bone marrow cells by classical method. Observe the incidence and severity of GVHD of different groups.

2. Clinical trial: 6 cases of HLA-haploidentical allogeneic PBSCT. 4 patients were transplantated with purified allo-CD34⁺ cells.

Next day, adjusted graft-receptor T cell ratios to 2:1 by infusing donor CD3⁺ T cells. Another 2 patient were treated with classical allo-PBSCT.

Results

1. Animal experiment: The severity of GVHD in group A1, A2 were lighter compared with group A3,B. The difference is significant among group A1,A2 and A3.

2. Clinical trial: An ultra-acute severe GVHD occurred in 2 patients who were transplanted with classical method.

They died from interstitial pneumonia secondary to PBSCT. The remaining 4 cases only presented mild aGVHD.Among these 4 cases, 3 patients had DFS (disease free survival) over 3 years, 1 patient died from polyradiculitis on +155d.

Conclusion: On the basis of our animal experiment, the appropriate graft-receptor T cell ratios would be 1:1 or 2:1. If we applied this ratio to clinical transplantation, especially to part HLA-related and HLA-haploidentical transplantation, we could obtained a better GVL effect and a lighter GVHD.