The Relative Percentage of Recipient T (CD3+) and Activated Lymphocytes (CD25+) Allows to Predict the Dynamics of Chimerism and the Risk of Complications after Allogeneic Stem Cell Transplantation

Introduction: The success of allogeneic stem cell transplantation (SCT) is conditioned by the dynamics and the result of the bidirectional interaction of immune reactions exerted by donor and recipient (alloreactivity/tolerance). Quantitative chimerism monitoring after SCT, mainly if performed on leukocyte lineages such as T lymphocytes (TL, CD3+), allows assessment of the immune interaction between donor and recipient.

Objective: To evaluate the usefulness of chimerism quantification in activated lymphocytes (AL, CD25+) for the early detection of complications (graft failure/rejection, GVHD, relapse, etc.) which, eventually, would improve the efficacy of current therapeutic strategies.

Material and methods: Chimerism quantification was done by microsatellite PCR (short tandem repeat, STR-PCR) on peripheral blood (PB) samples obtained every other week from 20 transplanted patients, as well as on leukocyte lineages, TL and AL, purified by immunomagnetic means (autoMACS, Miltenyi Biotec, purity>95%).

Results: Three different patterns of chimerism dynamics were observed:

• 10 patients showed complete chimerism (CC) in all samples analyzed post-SCT.

• 6 patients showed mixed chimerism (MC) with lower percentage of recipient cells in AL than in TL. All this 6 patients spontaneously evolved to CC.

• 4 patients showed MC with higher percentage of recipient cells in AL than in TL.

All these 4 patients showed decreasing MC (increasing percentage of recipient cells) in PB, TL and AL. Moreover, 3 of them showed complications involving the graft:

1. graft failure (not recovered after two succesive transplants) and

2. graft rejections (1 incipient), which recovered and achieved CC after donor leukocyte infusions.

Concerning disease relapse, 1 case was observed in each of groups A and B, and three cases were observed in group C.

Conclusions: Our results suggest that higher percentages of recipient cells in AL than in TL are associated with stronger host-versus-graft immune reactions and, therefore, with decreasing mixed chimerism and subsequently with various complications after SCT. On the contrary, lower percentages of recipient cells in AL than in TL predict the achievement of CC. Quantitative follow up of chimerism in AL (CD25+) increases the usefulness of the analysis of PB and TL (CD3+) samples, allowing to predict the dynamics of chimerism after SCT and favouring the early establishment of the appropriate therapeutic option in each transplanted patient.