CLL and Richter's Syndrome

[peas50]

I'm curious about the stats surrounding CLL 'morhping' into Richter's in 'younger' CLL patients. Would someone please point me in the right direction? Thanks

[djgolding]

Fewer than 5 out of every 100 people (5%) with CLL develops Richter's syndrome. According to Cancer Research UK, what it doesn't show is age profile.

[Cllcanada Top Poster CURE Hero]

I use the figure of 5% - 8% but some studies indicate 10%, one in Italy 14%, perhaps a high risk population.

Age has never really been looked at, but a study at ASH 2012, shows that the risk of RT increases every year after diagnosis... so the older you get, the greater the risk. The percentage increases after treatment, but RT is seem prior to treatment. The split was 45% pretreatment, 55% post.

You can read the abstract here.

ash.confex.com/ash/2012/web...

Richter's is generally poorly studied, with a median survival of 8-12 months, it is a bit hard to do many longterm studies...

The very best overview to date is the Jain, O'Brien study of 2013, which you can read here...

You must sign up to read these papers on the CancerNetwork... it is free and worthwhile doing so...

cancernetwork.com/review-ar...

Also Dr. Peter Hillmen

cancernetwork.com/articles/...

[peas50 in reply to Cllcanada]

Incredible information. Thank you so much for responding.

[SeymourB]

No matter what the percentages are in the overall population, since CLL is not a single disease, it's important to know what the percentages are for your form of it.

Looks like there are some additional risk factors, according to 1 recent paper listed here:

uptodate.com/contents/patho...

The full paper is behind a Wiley paywall. Here's the abstract:

ncbi.nlm.nih.gov/pubmed?ter...

"Risk of RS was associated with advanced Rai stage at diagnosis (P < 0·001), high-risk genetic abnormalitites on fluorescence in situ hybridization (P < 0·0001), unmutated IGHV (P = 0·003), and expression of ZAP70 (P = 0·02) and CD38 (P = 0·001). The rate of RS doubled in patients after treatment for CLL (1%/year). Stereotyped B-cell receptors (odds-ratio = 4·2; P = 0·01) but not IGHV4-39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three-fold (odds-ratio = 3·26, P = 0·0003)."

The lower the P values listed, the more confident they are of a connection with the symptom or marker.

Among the purine analogs are fludarabine.

Among the alkylating agents are chlorambucil and cyclophosphamide.

I think using both types at the same time is what increases risk.

So it looks to me like risk of Richters depends a lot on having the usual high risk forms of CLL, and the treatment used.

UpToDate is a new site to me, and I'm not a subscriber.

=seymour=

[Cllcanada Top Poster CURE Hero in reply to SeymourB]

Very true... the devils are in the details....

Here is the full paper you sited Seymour

carmenwiki.osu.edu/download...

New research indicates

Trisomy 12, NOTCH1 and or FBXW7 mutations stereotyp B cell receptors, IGHV4-39*01 may all increase risk of RT as well.

Ethnicity matters... telomere length matters, tomorrow something else...

Here is an interesting snapshot from India... median age 47 years for RT. But this is a very different population than say Houston or Tel Aviv.

journal.sajc.org/temp/South...

~chris

[SeymourB in reply to Cllcanada]

Chris -

Thanks so much for the paper! You Canadians are such nice people!

I was hoping to get registered at the local community college this semester, so I would get access to journals through the Louisiana State university system. But it turned out that my high school senior son suddenly was able to register for dual enrollment at the college, and so I lost my funding. I may borrow his account

Meanwhile, I'm doing MOOCs on genetics, immunology, and music (must feed the soul).

=seymour=

[Cllcanada Top Poster CURE Hero]

Here is a Patient Power video, where Dr. Bill Wierda from MD Anderson, discusses Richter's Transformation. Interest he uses the figure of 10%-15% of patients will transform from their database findings... but the CLL population may be skewed because they likely see more high risk 17p than the average community hospital...

patientpower.info/video/wha...