Early Mixed T-Cell Chimerism After Allogeneic Hematopoietic Stem Cells Transplantation Is Highly Predictive For Progression Free Survival

Chimerism analysis after allogeneic hematopoietic stem cells transplantation (HSCT) allows documentation and understanding of important clinical events such as engraftment, graft failure, and/or relapse. Few data are available on whether T-cell chimerism might be more informative than global chimerism. In this study, we focused on selective CD3+ T-cell chimerism and its interest to predict events after allogeneic HSCT.

This is a single center retrospective study. Only patients with a survival more than 3 months were included. Information concerning donors, recipients, conditioning regimen, graft harvesting and follow-up were collected in our center using prospective forms from Promise database. Evaluation of T-cell chimerism was performed on CD3+ blood cells after immunomagnetic sorting, by PCR-STR (short-tandem repeats) multiplex technique using 15 different markers. Analysis of the tandem repeat polymorphism was performed by sequencer and Genscan software (Applied Biosystem Inc.). Chimerism was evaluated in 2 ways: positive or negative, and % of recipient. An analysis with repeated measures was also performed to determine the utility of a positive measure of chimerism, independently of the date of sample after allograft, to predict a relapse.

Between January 2006 and December 2011, 148 patients (pts) were admitted in our unit for allogeneic HSCT (32% with myeloablative conditioning and 68% with reduced conditioning). Median age was 54.3 years, 59 male, 89 female. Diagnosis included AML/MDS (n=77), ALL (n=23), Aplastic anemia (n=4), lymphoma and CLL (n=23), myeloma (n= 8) and myeloproliferative disorders (n=13). The donor was matched sibling (n=51), matched unrelated (10/10) (n=74) or mismatched unrelated (9/10)(n=23). Graft source was PBSC (n=97), BM (n=33) or CB (n=18). At transplant, 108 pts (73%) were in complete remission, 19 (13%) presented partial response and 21 (14%) have progressive disease. At time of analysis, median follow-up was 1.75 years. Median overall Survival (OS) was estimated at 2 years. Forty-seven pts (32%) presented relapse. Seventy pts (47%) are still alive. Main causes of death were HSCT related (n=38), relapse or progression (n=33) and other (n=7). Acute GVHD grade II-IV incidence was 32% (13.5% grade III-IV) and 58% for chronic GVHD. At day +30, 56% of pts presented a mixed T-cell chimerism with 36 (24.3%) pts with a chimerism higher than 25% recipient. At day +90, 41% have remained positive. For NRM, aGVHD and age were the only prognostic parameters statistically identified. For PFS, only T-cell chimerism with a positive 25% cut-off at D+30 was identified as a prognostic factor (p=.0017, HR(IC 95%) 2.52(1.39; 4.58). PFS was not reached if T-cell chimerism was inferior to 25% at D+30 versus 1.35 years (figure 1). The results were concordant in a subgroup analysis performed according to the myeloid or lymphoid neoplasia status. Otherwise, cGVHD incidence was higher if T-cell chimerism was less than 25% at D+30 (70% vs. 18%). Finally, the analysis with repeated measures confirmed that positive T-cell chimerism is strongly correlated with relapse (p=.001; HR (CI95%) 90.18(30.11; 270.13)).

After allogeneic HSCT, mixed T-cell chimerism higher than 25% at day +30 is strongly correlated with poor PFS, independently of source of cells, donors, intensity of conditioning, diagnosis or disease status at transplant. Considering this high-risk population, early intervention should probably be considered.

Figure 1

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PFS (years) consdering value of T-cell chimerism at Day +30 after allogenic HSCT.

Figure 1

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PFS (years) consdering value of T-cell chimerism at Day +30 after allogenic HSCT.

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No relevant conflicts of interest to declare.