Very interesting article on TR with Dr. Elias Campo among other doctors. Article published by the journal Nature. Posted on August 11. Read it because it gives a lot of information and within this study we are myself and two other people from this group among other cases that we offered ourselves for study. Many of you will see yourselves reflected in this article.
nature.com/articles/s41591-...
Richter’s Transformation Facebook
"Altogether, these findings show that RT may arise simultaneously from different subclones and that such subclones can be detectable time before their final expansion and clinical manifestation. The identification of mutations in RT associated with early-in-time CLL therapies demonstrates that RT emerges from the clonal expansion of a single cell previously exposed to these therapies."
An interesting but complex study to understand.
Thank you for posting it.
I don't understand half of it, but some expert can summarize what it explains. I am pressuring researchers to study RT more because there are more and more cases and that it is not an isolated case.
Does that mean that RT only applies to patients who underwent therapy already? Or can one transform while on watch and wait?
It means that they can ensure that patients who are prone to having RT can be treated so that once the transformation appears, it does not develop.
Thank you, and who is prone to having RT?
Hello LeoPa
When I was diagnosed with possible RT. The symptoms were rapid growth of CLL, bulky lymph nodes. I had ALC doubling every 2.5 months and massive bulky lymph nodes of 16cm x 18cm x 22cm. At my CLL Specialist's suggest to my H/O, I had PET scan performed to verify RT rather than lymph node biopsy. CLL Specialist suggested that my LDH was verify stable and not high enough for RT. As was explained to me by CLL Specialist doctors, the PET scan uses a high sugar contrast die that "lights UP" the bodies organs with cancer tumors. RT is spread of fast-growing cancer cells to body from lymph nodes creating large cell lymphoma. RT however unlike CLL, can in small percentage of cases be cured. Fortunately, in my case I did not have RT per pet scan. PET scan was from chin to bottom of genitals.
Hello. You have to know how to identify a true RT to an aggressive CLL. It is the case that they are treating people with chemotherapy because the doctors do not know how to identify the cells of an aggressive CLL and consider it to be a RT due to its rapid growth. In my case, every time my CLL returns, its speed is in less than six months and the nodes are enormous.
Thank you, very informative. I'm glad you did not have RT 🙏.
The rapid expansion of RT subclones under treatment with BCR inhibitors is consistent with its low BCR signaling, except when carrying the IGLV3–21R110 and further supported by the increased number of subclones carrying unproductive immunoglobulin genes and the development of RT with plasmablastic differentiation, a cell type independent of BCR signaling60.
Finally, we also uncovered that OXPHOS inhibition reduced the proliferation of RT cells in vitro, a finding worth exploring in future therapeutic strategies55,57.
this is interesting
More than just a lot of information in this publication.
Though from a patient's observation perspective, It does provide hope in showing that there is an extensive effort being made in the research community to understand a very complex disease transformation relative to CLL.
This is a good indication that these researchers are brilliant and compassionately dedicated to finding a treatment.
Thanks again Priss!
JM
I have been fighting for three years to get to study the TR. Dr. Elias Campo knew about my case and got funding to investigate the Richter Transformation but they lacked enough cases and he didn't have them. I got him three cases with the corresponding biopsies.
I will continue fighting so that this terrible transformation that we all fear stops being a bad prognosis.
A hug
Priss
Thank you for your work, It takes a special person to do what you are doing! Thanks for posting the article as well, my biology is rusty but I can certainly draw encouragement from the fact that people much smarter than me are working on prevention.
You're awesome Priss, thank you very much for all your work on this topic.
Thank you very much for taking the trouble to read the information I provide. It is something that can happen to all of us.
IT'S MY WORSE NIGHTMARE.
Priss how are you doing? You have done a lot for people with RT who were not getting a whole lot research and information availability. Good for you 👍🏻
What was very good information was the possibility to do testing at the time of original diagnosis to find RT possible mutation and treat it before it actually happens. That might eliminate RT🤞🏻and the fear of it we all dread.
I remember when you first joined after just having a baby. I hope all is going well for you Priss.
Happy Thanksgiving to you and yours from Canada 🍁
Dana
hi dana
Little is known about the RT and it was a death sentence three years ago. I try to bother the doctors a lot so that they investigate and continue investigating because every day there are more RTs and few people had investigated because they said they would die soon and that is false. In our group there are people who have been in complete remission for six years.
We must continue fighting so that it is diagnosed soon and can be cured as a lymphoma and not as RT.
Hi, This article is too far above my comprehension. It is very complex. I did see something that is concerning to me which is the sentence
" The rapid expansion of RT subclones under treatment with BCR inhibitors is consistent with its low BCR signaling, except when carrying the IGLV3–21R110 and further supported by the increased number of subclones carrying unproductive immunoglobulin genes and the development of RT with plasmablastic differentiation, a cell type independent of BCR signaling60. "
I have had CLL for about 7 years and am currently W&W. I do carry the IGLV3-21. To the more scientifically learned members of the group does this mean that those of us with IGLV 3-21 have a greater chance of RT after treatment?
Thanks,
Pat
I think it's the opposite. "The rapid expansion of X (leading to RT) when being treated with Y type drugs, except when the patient has "X carrying the mutation Z". You say you have mutation Z. Someone please comment if I am wrong, my anemia is giving me some problems with my mental processes lately.
And this is specific only to treatment with BCR inhibitor type drugs (BTK and BCL2 currently). So the antiCD20 and things like bendamustine/methotrexate or other standard chemotherapeutic agents may work around this, other factors taken into account. You don't say any of your markers, so IDK if say a del17p is in play. Or if you are mutated/unmutated IGHV. So BR, or Gazyva or Rituxan alone, may be a consideration.
And this is a prime example of why we still need the PI3K inhibitors. Perhaps not as first line treatment if they have "more toxicity", but still available. Because IMO standard chemotherapeutic agents can be the most overall toxic of all, and many of us have cancers that even these meds won't affect very much.
I am mutated. Negative for CD38, 17p TP53 not detected. In 2018 my ALC was 6.07 and it is now 11.79. WBC has fluctuated between 11 and 17. Currently 15.94. Immunoglobulins declining and am IVGH 3-21.
I note from your bio, that you were diagnosed in November 2017, but consider that you probably had CLL for two years prior to that from your blood test results. From: Study of VH3-21 in a Large Cohort of Chronic Lymphocytic Leukemia Patients Reveals Evidence for Antigen Selection and Confirms Its Predictive Value for Early Disease Progression
ashpublications.org/blood/a...
We examined the time from diagnosis to initiation of therapy as per established NCI-Working Group guidelines in 40 patients for whom complete clinical data were available. With a median follow-up of 4.2 years from the date of diagnosis, 25 of the 40 patients had received therapy at the time of this analysis. The median time to treatment (TTT) for all 40 patients was 3.5 years, which was significantly shorter than the median TTT of 6.6 years noted for a previously-described CRC cohort of 307 patients that were not selected for use of IgVH3-21 (NEJM 2004; 351: 893–901) P<0.001).
So you have exceeded the median for this study group of VH3-21 patients and are approaching that of those in another group, not selected for VH3-21. This just goes to prove that markers are predictive for groups, not individuals, which is a comfort that I think many of us appreciate.
Neil
Thank you Neil
There was some earlier discussion about this very interesting research that may be helpful, too. Here's the link:
Chronic lymphocytic leukemia
Leukaemia Care Updated Patient Information - Richter's Syndrome in Chronic Lymphocytic Leukaemia 
