Treatment of Chronic Lymphocytic Leukemia with TP53 Aberrations


Authors: D. Lysák 1;  J. Schwarz 2
Authors‘ workplace: Hematologicko‑onkologické oddělení, FN Plzeň 1;  Ústav hematologie a krevní transfuze, Praha 2
Published in: Klin Onkol 2015; 28(Supplementum 3): 39-44
doi: 10.14735/amko20153S39

Overview

Patients with chronic lymphocytic leukemia with deletion of the short arm of chromosome 17 (17p‑ ) or mutation of the TP53 gene have significantly worse prognosis with a higher risk of progression to symptomatic disease, worse and shorter responses to chemo‑ immunotherapy, and more frequent occurrence of Richter‘s syndrome. TP53 deletion/ mutation is currently the only genetic abnormality that independently predicts response to treatment and also affects the choice of therapeutic approach in chronic lymphocytic leukemia. This work summarizes treatment options available for this poor prognosis variant of chronic lymphocytic leukemia. Traditional chemo‑ immunotherapy (e. g. FCR) does not offer long‑term disease control, and patients with TP53 deletion/ mutation were usually considered to undergo allogeneic bone marrow transplantation. New molecules from the group of BCR inhibitors or BCL2 antagonists achieve excellent efficacy in chronic lymphocytic leukemia with del17p even in relapsed/ refractory (R/ R) cases, with a higher percentage of responses and prolonged survival without progression. Clinical trials are ongoing to determine optimal therapeutic approach and to induce long‑term remission of the disease. The new molecules change algorithms for treatment of patients with TP53 aberration, including indication for allogeneic transplantation. Especially younger patients should be consulted in centers of intensive hematological care to consider their inclusion into clinical trials testing new molecules or to indicate allogeneic transplantation at the optimal time.

Key words:
chronic lymphocytic leukemia –  risk factors –  deletion 17p –  TP53 –  transplantation

This study was supported by the Charles University Research Fund (project number P36) and by the project of Ministry of Health, Czech Republic –conceptual development of research organization (Faculty Hospital in Pilsen – FNPl, 00669806).

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
4. 8. 2015

Accepted:
5. 8. 2015


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