Recent thymic emigrants and prognosis in T- and B-cell childhood hematopoietic malignancies

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Abstract
The concentration of T‐cell receptor rearrangement excision DNA circles (TRECs) in peripheral blood mononuclear cells (PBMCs) is currently known to be a marker of recent thymic emigrants. We evaluated the hypothesis that TREC values would be lower in childhood T‐cell hematopoietic malignancies than in childhood B‐cell acute lymphoblastic leukemia (ALL) or healthy controls because the former category may reflect compromised thymic function. From the Greek national childhood leukemia/lymphoma database we obtained all 30 available T‐cell leukemia/non‐Hodgkin's lymphoma cases, 30 age‐ and sex‐matched childhood B‐cell origin cases of ALL and 60 healthy hospital controls. We compared TREC levels in PBMCs using a real‐time PCR assay. There was highly significant reduction of TREC values in children with T‐cell malignancies (median 3,100 TRECs/106 PBMCs), whereas children with B‐cell origin ALL had slightly but nonsignificantly lower TREC values compared to healthy children (medians 19,300 and 22,500 TRECs/106 PBMCs, respectively). During a median follow‐up period of about 19 months, only 4 children died. All of them had a T‐cell hematopoietic malignancy and relatively low TREC values. The number of TRECs was higher among healthy girls than among healthy boys, and a similar pattern was evident in T‐cell malignancies. It appears that there is a pattern of concordance of high TREC values with better disease prognosis in hematologic childhood malignancies. This applies to specific disease entities with better prognosis (B‐cell origin ALL having higher TREC values than T‐cell leukemia/lymphoma) and to gender, another important predictor of prognosis conditional on disease entity (girls having higher TREC values than boys); however, it may also be true for the survival of individual patients. These preliminary findings can be used as hypothesis‐generating indications that should be confirmed in larger data sets.
Funding Information
  • Europe Against Cancer Programme (SOC96-200505-05F02)
  • National Institutes of Health (RO1 AI43868)