Acute Gvhd Is a Strong Predictor of Full Donor cd3+ t Cells Chimerism (TCC) After Reduced Intensity Conditioning (RIC) for Allogeneic Stem Cell Transplantation (Allo-SCT)

Abstract 4545

The monitoring of chimerism is a standard procedure for assessing hematopoietic engraftment and achievement of full donor lymphoid chimerism after RIC based Allo-SCT. Post graft donor lymphocyte infusions are often decided on this evaluation. These studies have however a cost issue, all the more no consensus presently exists on when and how often to perform them.

We retrospectively analysed the impact of acute GvHD in the prediction of allograft chimerism in our RIC program where TCC was serially assessed at 30, 60 and 90 days after Allo-SCT. We selected patients with hematologic malignancies (with the exclusion of myelofibrosis) transplanted between 2001 and 2010 after Fludarabine-Busulfan-ATG RIC from a HLA identical donor. 115 patients fulfilled all criteria including at least one T cells chimerism (TCC) determination between day 30 and 120. Allo-SCT was performed from familial donor in 92 patients (80%) and from MUD in 23 patients (20%). The conditioning regimen consisted of fludarabine (90 to 180 mg / m²), Busulfan (8 mg / kg orally or 6.4 mg / kg IV) and rabbit anti-thymocyte globulin (ATG) (2.5 or 5 mg /kg). As for chimerism study, recipient peripheral blood T lymphocytes were positively sorted by a mix of anti-CD4 and CD8 immunomagnetic beads (Dynal, Compiègne, France). T-cell purity was controlled by flow cytometry and was always > or =95%. Genomic DNA was amplified using fluorescent PCR primers for polymorphic variable number tandem repeats (VNTR) or short tandem repeats (STR). Mixed T-cell chimerism was defined as between 5 and 94% recipient cells, and full chimerism was defined as the presence of more than 95% donor cells.

Full TCC was achieved in 94 patients (82%) at a median of 77 (30–120) days post transplant.

Fifty eight patients (50.4%) developed acute GvHD. The cumulative incidence of Grade 2–4 GvHD in our population is 32% (95% CI 23–41).

Overall the results showed that each of the 37 patients developing grade ≥ 2 AGVHD had a Full TCC prior day 120. On the other hand, all mixed chimerism were documented in patients not presenting Grade≥2 AGVHD (21 of the 78 patients (27%) without grade ≥ 2 AGVHD) (p=.002). No other parameter (ATG dose, Donor type…) achieved this level of individual prediction.

These results, in a very homogenous population, are in line with the concept that full TCC is more likely to occur when patient develops significant aGVHD. Although they deserve further and deeper confirmation in different populations, they address the value of systematic routine chimerism surveillance (outside clinical studies) in patients presenting acute GvHD following RIC Allo-SCT. The modulation of TCC determination might represent an interesting cost and resources saving.