Research Evaluating Risk of Richter Syndrome

[jonathan7176]

Apologies if this has been posted before, do feel free to delete and re-direct me if so. It is of particular interest to me because my recent experience suggests that the NHS does not test for complex karyotype CLL (using Chromosome Banding Analysis). I know only that I had an aggressive presentation, that I am 11q and assumed to be un-mutated, though I do not know that for sure. So, can the NHS determine whether I have a complex karyotype or not? Is that something I'd necessarily want to know? And, does this research seem methodologically sound?

The article is free to view at ncbi.nlm.nih.gov/pmc/articl.... Abstract is as follows:

"Complex karyotype (CK) at chronic lymphocytic leukemia (CLL) diagnosis is a negative biomarker of adverse outcome. Since the impact of CK and its subtypes, namely type-2 CK (CK with major structural abnormalities) or high-CK (CK with ≥5 chromosome abnormalities), on the risk of developing Richter syndrome (RS) is unknown, we carried out a multicenter real-life retrospective study to test its prognostic impact. Among 540 CLL patients, 107 harbored a CK at CLL diagnosis, 78 were classified as CK2 and 52 as high-CK. Twenty-eight patients developed RS during a median follow-up of 6.7 years. At the time of CLL diagnosis, CK2 and high-CK were more common and predicted the highest risk of RS transformation, together with advanced Binet stage, unmutated (U)-IGHV, 11q-, and TP53 abnormalities. We integrated these variables into a hierarchical model: high-CK and/or CK2 patients showed a 10-year time to RS (TTRS) of 31%; U-IGHV/11q- /TP53 abnormalities/Binet stage B-C patients had a 10-year TTRS of 12%; mutated (M)-IGHV without CK and TP53 disruption a 10-year TTRS of 3% (P<0.0001). We herein demonstrate that CK landscape at CLL diagnosis allows the risk of RS transformation to be refined and we recapitulated clinico-biological variables into a prognostic model".

Many thanks

Jonathan

[AussieNeil Administrator]

Hi Jonathan,

Given you know that you are 11q deleted, you have had FISH testing done*. If you have no other deletions, then you are not complex karyotype. The 2021 study you cited followed 540 people with CLL. This much larger study from 2019, which followed nearly ten times as many people with CLL, ncbi.nlm.nih.gov/pmc/articl...

states that "Complex karyotype defined by the presence of ≥3 chromosomal abnormalities should not be axiomatically considered unfavorable in CLL" . As you appreciate, a significant influencing factor in your likely time to first treatment is your IGHV mutation status, though your CD38 expression (from your immunophenotype flow cytometry diagnostic testing for CLL) is also an independent factor. Being CD38 negative is associated with a longer period in watch and wait.

IGHV mutation status in the UK is pretty well only relevant if you are keen on having FCR treatment. Whether there's an influence on the choice of targeted therapy treatment is still being determined.

*That's not generally the case in the UK, because FISH test results influence treatment choice and can change over time. That's why FISH testing is most often first done in the UK when treatment is planned.

Neil

[jonathan7176 in reply to AussieNeil]

Thanks Neil - I had inferred from that paper that FISH isn't sufficiently refined to clearly identify karyotype? But yes, FISH showed me to be 11q deleted only. Quite enough. 😂

[Sushibruno in reply to AussieNeil]

hello Neil, is it common for fish to change with cll?

[AussieNeil Administrator in reply to Sushibruno]

It was considerably more common back when 'chemo' was the only treatment. There was a higher incidence of 17p deletion sub-clones caused by treatment. You are mutated 13q deleted, so with that very stable form of CLL, you would be unlikely to see a change in your FISH results.

Neil

[Sushibruno in reply to AussieNeil]

thanks Neil