Evaluation of Minimal Residual Disease (MRD) in Children with T-Lineage Acute Lymphoblastic Leukemia

Abstract

In acute leukemias malignant cells derived from the sole parent cell that underwent neoplastic transformation share identical configuration of Ig and TCR genes. Monoclonal rearrangements of Ig and TCR genes comprise unique features of the given leukemic clone, thus allowing the basis for monitoring of the minimal residual disease (MRD) using polymerase chain reaction (PCR) method in acute lymphoblastic leukemias [1,4,7,14,22]. Results of several clinical studies indicate that detection of residual leukemic cells in ALL correlates positively with relapse [5,10,14,20, 21,22]. Acute T-cell lymphoblastic leukemia is a clinically homogenous disease with high rate of treatment failures. Thus, T-cell immunophenotype is considered as an unfavourable prognostic factor. Intensification of treatment in that group of patients produced current results comparable with those achieved in patients with non- T-ALL [14,15,16]. Occurrence of relapse reflects ineffectiveness of chemotherapy and allogenic bone marrow transplantation is probably the only chance for cure. Ability to identify the population at risk of relapse would allow early alternative treatment. In that context TCRδ and TCRγ gene rearrangements represent the optimal target for monitoring of MRD using PCR assay in patients with T-ALL, since at least one allele is rearranged in 95% of patients and remains stable in more than 90% of cases [3], Also TCRδ gene rearrangements, present in 70% of patients with T-ALL, show limited potential of variety, thus allowing the use of procedures that detect patients with positive results, and vast diversity of junctional sites allows preparation of patient- specific probes [2,3], Studies performed by Dibenedetto et al. showed that residual malignant cell might be detected in PCR test 12-15 weeks after completion of induction therapy in almost all patients (94%), regardless of the therapy protocol [8]. Their analysis confirms the observation that presence of MRD 30-40 weeks after diagnosis is a predictor of poor prognosis. On the contrary, lack of residual leukemic cells in any time point after diagnosis is correlated positively with favourable prognosis. In this prospective study we investigated the group of 18 patients with childhood T-cell ALL in various time points of BFM 90 treatment protocol. We applied the method of polymerase chain reaction previously described by Vandenvelde et al. and Taylor et al. [18,19]. The aim of the study was to answer the question whether the presence of MRD in children with T-ALL might influence the outcome.