Abstract
BackgroundThymus-dependent T-cell reconstitution plays a role in immune recovery after stem cell transplantation (HSCT). High pre-HCST thymic function has been associated with higher survival, lower incidence of acute and chronic graft versus host disease (GVHD) and lower incidence of infections. The aim of this study was to analyze the relationship between pre-HSCT peripheral blood levels of T-cell receptor excision circles (TREC) and post-HSCT clinical events in recipients of HLA-identical hematopoietic stem cell transplants.MethodDelta deletion signal joint TRECs (sjTRECs) formed by the dREC-yJa rearrangement were quantified by real time PCR in peripheral blood lymphocytes of 62 HSCT recipients.ResultsUnivariate analysis revealed an association between low TREC levels and a higher incidence of grade II-IV acute GVHD (p=0.026), bacterial infection (p=0.005) and cytomegalovirus infection (p=0.033), whereas high TREC levels were associated with higher overall survival (p=0.028). In the multivariate analysis, low pre-HSCT TREC levels remained independently associated with lower survival (p=0.032; RR 2.6), occurrence of grade II-IV acute GVHD (p=0.031; RR: 2.5), bacterial infection (p=0.006, RR: 6.6) and cytomegalovirus infection (p=0.039; RR:2.8).ConclusionOur results corroborate the concept that pre-HSCT recipient´s thymic function is an important predictor of risk for acute grade II-IV GVHD and infection.
Highlights
A hematopoietic stem cell transplant (HSCT) is an effective treatment for several types of malignant blood diseases, it can cause a number of different side effects, mainly related to opportunistic infections and graft versus host disease (GVHD)
T-cell receptor excision circles (TREC) levels and high/low risk disease the pre-transplant TREC levels have been previously associated with post-transplant prognosis[24], we sought to repeat this analysis in our population of patients because it had a much bigger proportion of malignant high-risk diseases (27% vs 1% in 24)
TREC levels and survival Using the receiver-operating-characteristic (ROC) curve, we found a cut-off value of 134 TREC/μg of lymphocyte DNA that discriminated between patients that survived or not for at least 6 months after transplantation (65% of sensitivity and 60% of specificity)
Summary
A hematopoietic stem cell transplant (HSCT) is an effective treatment for several types of malignant blood diseases, it can cause a number of different side effects, mainly related to opportunistic infections and graft versus host disease (GVHD). It has been suggested that the reconstitution and maintenance of effective T-cell immunity after HSCT is dependent on education about T-cell precursors in the thymus, as shown by the correlation between increased thymic output and an increment in naïve T-cells, and broader TCR repertoires after transplantation[13,14,15]. Thymus-dependent T-cell reconstitution plays a role in immune recovery after stem cell transplantation (HSCT). The aim of this study was to analyze the relationship between pre-HSCT peripheral blood levels of T-cell receptor excision circles (TREC) and post-HSCT clinical events in recipients of HLA-identical hematopoietic stem cell transplants. Method Delta deletion signal joint TRECs (sjTRECs) formed by the dREC-yJa rearrangement were quantified by real time PCR in peripheral blood lymphocytes of 62 HSCT recipients
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