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Posted by on Mar 11, 2018 in Leukemia | 0 comments

In a nutshell

This study examined causes and outcomes of a chromosomal abnormality known as 17p deletion in chronic lymphocytic leukemia (CLL). Researchers reported poor outcomes for patients that have both 17p deletion and 8q24 gain.

Some background

Certain genetic changes in CLL can make it more difficult to treat. Changes in the chromosomes, such as damaged or missing parts, are present in about 80% of CLL patients. Some chromosomal changes can lead to the loss of chromosome 17 and one copy of the TP53 gene. This is known as 17p deletion and can be particularly aggressive. It is found in less than 10% of CLL patients but in up to 40% of cases where treatment is no longer working or where there is a relapse (return of the disease). A better understanding of the cause of 17p deletion and any knock-on effects is needed. 

Methods & findings

195 CLL patients with 17p deletion were included in this study. 77% of patients showed 17p deletion at diagnosis. In 23% of patients, 17p deletion developed after treatment. The TP53 gene was mutated in 92% of patients. On average, patients had undergone 2.5 previous lines of treatment. All patients were tested for any additional genetic abnormalities. The study followed treatment outcomes for an average of 70 months.

In 70% of patients, 17p deletion was the result of an unbalanced rearrangement of chromosomes. 23% of patients showed a full deletion of 17p. In 8% of cases, one member of a pair of chromosome 17 was missing (called monosomy). In 2% of cases, the ends of chromosome 17 fused together to form a ring.

The average time to disease progression after the end of treatment was 18 months. For patients with high-risk disease (Binet stage B or C) this treatment-free survival time decreased 6-fold. Having the monosomy 17 version of 17p deletion decreased treatment-free survival by about half. The same was noted for patients with more than 5 chromosomal abnormalities overall.

The biggest risk factor was having an additional chromosomal abnormality called 8q24 gain. It decreased treatment-free survival 6.5-fold. Further analysis that controlled for other factors showed that 8q24 gain remained a significant predictor of poor overall survival.

The bottom line

This study concluded that 8q24 gain is a strong predictor of poor survival in CLL patients with 17p deletion.

Published By :

American Journal of Hematology

Date :

Dec 01, 2017

Original Title :

“Double-hit” chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.

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