AL-09. Significance of immunophenotypic markers in adult patients with T-cell lymphoblastic leukemia

Summary

Since 2017, in the WHO classification, a new variant has been identified – early T-cell precursor ALL (ETP-ALL) with a unique immunophenotype (absence of CD1a and CD8 expression, low (<75%), CD5 expression, presence of expression of one or more stem cell or myeloid precursor markers) and unfavorable prognosis. In recent years, in addition to ETP-ALL, a group with unfavorable prognosis, called near-ETP, has been singled out; their difference from ETP-ALL lies in the brightness of CD5 expression (>75%). Our aim was to determine the value of distinguishing different T-ALL variants in adult patients who received therapy in the multicenter randomized prospective study RALL-2016.

Materials and methods

From December 2016 to June 2023, 108 patients with T-ALL/LBL were included in the study. Of these, 78 (72%) were males and 30 (28%) were females. Distribution into variants: 22 (20%) were ETP, 9 (8%) were near-ETP, 24 (22%) were T I/II, 48 (44%) were T III, and 5 (4%) were T IV.

Results

The median age in all groups was similar, amounting 30.5 years (in the TI/II group) and 36 years (in the near-ETP group). The median leukocyte was the highest in the TIII and TII groups at 48.5 and 48 thousand cells/µL, respectively, and the lowest in the near-ETP group at 9.5 thousand cells/µL. The highest value of median LDH was found in group T III and amounted to 1468 U/L. The study involved randomization for patients with T-ALL: 36 patients were randomized to auto-HSCT with further continued chemotherapy; 37, to continued chemotherapy without auto-HSCT. The distribution in auto-HSCT group was as follows: ETP, 4 (2 performed allo-HSCT); near-ETP, 2 cases; T I/II, 11 patients; T III, 16 cases; T IV, 3 patients. The case distribution in the chemotherapy group: ETP, 6 (2 performed allo-HSCT); near-ETP, 2; T I/II, 3 cases; T III, 25 cases; T IV, one patient. The cases from near-ETP group were evenly distributed both to auto-HSCT group and to chemotherapy. The number of patients with specific mediastinal lesions was lower in the group with earlier disease variants (ETP – 45%, T IV – 80%), while specific CNS involvement in them was significantly more frequent (ETP – in 7 patients (31%); T IV – none). Abnormal karyotype was most frequently found in the ETP (17 patients, 77%), near-ETP (5 cases, 55%), and T III (21 patients, 55%). At the same time, complex rearrangements were detected only in 3 patients (14%) from the T III group, and in the ETP, in 5 patients (30%); near-ETP, in 2 cases (40%). The overall 3-year survival rate was significantly better in the T III patients versus other groups: ETP, 46%; near-ETP, 56%; TI/II, 58%; T III, 86%; T IV, 60% (Fig. 1). ETP and near-ETP were found to be the most unfavorable groups when evaluating the 3-year relapse-free survival: ETP (56%), near-ETP – (62%); T I/II (79%), T III (94%); T IV (75%) as seen in Fig. 2.

Conclusion

ETP was considered an unfavorable variant by WHO in 2017. According to the clinical recommendations, intensified therapy with inclusion of allo-HSCT is indicated for ETP in the first remission of the disease. Taking into account the results of the study about high relapse rate in patients with near-ETP compared to ETP group on the basis of standard chemotherapy, it is likely that this group of patients should also be classified into a high-risk group of relapse and should be considered for allo-HSCT in the 1^st remission.

Keywords

Acute lymphoblastic leukemia, immunophenotype, early T cell precursors (ETP), near-ETP group.