Features of the course of chronic lymphocytic leukemia in the presence of a genetic mutation of leukemia cells: 17p13 deletion and its impact on disease prognosis.

Abstract

e19515 Background: In order to identify the features of the course of the disease in patients with chronic lymphocytic leukemia (CLL) when prescribing standard polychemotherapy (PCT) according to the RFC scheme (rituximab, fludarabine, cyclophosphamide) we investigated chromosomal aberrations in leukemia cells. Methods: We observed 190 patients (aged 57.4±23.7 years, 87 men, 103 women). Cytogenetic studies were conducted. Clinical and hematological remission was evaluated. Results: 52% of patients had single chromosomal aberrations, 25% - double, 23% - complex. A deletion of 17p13 (del (17p13)) with a level on leukemia cells from 2 to 98% in the period from the moment of CLL diagnosis of 11.8±7.2 months was found in 85 people (44.7%), with a level of more than 15% - in 24 (12.6%), of which with a level of 21% - 98% - in 12 (6.3%). During standard PCT according to the RFC scheme, among 44 patients with a level of cells with del (17р13) less than 15%, when controlled after 12 months, 12 (37.5%) showed an increase in the number of these cells to an average of 22.5%, which correlated (p < 0.1) with early relapses of the disease and the formation of secondary resistance to cytostatic treatment; in 20, there was no correlation between an increase in the number of cells and progression (partial remission (PR) was achieved); in 12 patients, cells with del (17p13) were not detected, and patients were characterized by the achievement of complete clinical and hematological remission (CR), which indicates the effectiveness of the FCR scheme in most patients. In 12 patients with the level of cells with del (17p13) 21% - 98%, no statistically significant increase in them was detected after 12±3 months (p > 0.15), however, remission was not achieved. They were treated with ibrutinib. Among the 8 patients with a recurrent course while taking ibrutinib at a dose of 420 mg per day for 2 to 4 years, severe infections were observed in the first months of therapy; in 4 patients the number of infectious episodes reduced later. 4 achieved PR (50%), 3 - PR (37.5%), 1 - stabilization. Conclusions: Thus, the level of blood cells with del (17p13) less than 15% in patients with CLL does not determine the severity of the disease and sensitivity to cytostatic treatment. These patients in the first line of chemotherapy are indicated for R, which, as a rule, does not cause irreversible elimination of cells with del (17p13), but slows down the growth of the tumor clone. This may determine the achievement of longer CR and PR and lead to a significant improvement in the long-term prognosis of the disease, and therefore the widely used RFC chemotherapy for B-CLL remains effective in most primary and pretreated patients. The detection of forms with a 17p13 deletion in an amount of more than 15% among tumor leukemia cells makes it possible to select a group of patients for prescribing ibrutinib, the overall response rate in which was 87.5%.