Quantitative Analysis of TREC and KREC Molecules in Patients with Acute Lymphoblastic Leukemia at the Stage of Maintenance Therapy

Background and Aims Maintenance therapy (MT), which aims to destroy the remaining tumor cells after hematopoietic stem cell transplantation (HSCT), is the final stage of treatment for acute lymphoblastic leukemia (ALL). The restoration of naive T lymphocytes is extremely important after HSCT because it provides a wide variety of T cell receptor repertoire, which is necessary to avoid recurrence of the leukemic clone. The recovery of both naive T and B lymphocytes can be demonstrated by measuring TREC/KREC-positive cells Methods The group of patients receiving maintenance therapy after going into remission included 18 patients (male, 11; female, 7) with ALL. According to the immunophenotype ALL: common B (n = 14), cortical T cell ALL (n = 2), pre-B cell (n = 2). According to the FAB classification, 6/18 (33%) had stage L1; the remaining 12/18 (67%) had stage L2. Peripheral blood for analysis was collected from patients at the time of MT, regardless of the date of initiation of treatment; thus, the median time when the material was collected was 9 (1.2 to 15.8) months. Quantitative analysis of TREC and KREC molecules was performed by RQ-PCR. Results During 1.5 years of maintenance therapy in patients with ALL, the TREC count increases but does not reach normal values. B lymphocytes, in turn, recover extremely slowly and have extremely low values in all patients studied. In 5/18 patients, B cells were not detected at all. Reliable differences were found between the KREC content in patients receiving PT and healthy donors (p < 0.0001), as well as between the KREC and TREC counts in these patients. It was found that at the stage of remission induction on day 22, there is a reliable decrease and redistribution of the subpopulation composition of T and B lymphocytes, which continues until the end of consolidation. After the cancellation of high-dose chemotherapy, lymphocytes begin to gradually recover, but the rate of T lymphocytes significantly exceeds that of B lymphocytes. Conclusions Quantitative analysis of TREC and KREC molecules allows us to judge the renewal of the pool of naive T and B lymphocytes without the use of additional immunological research methods. This method can be used at the stage of maintenance therapy to monitor immune reconstitution.