Richter's syndrome (My luck may just be running out)

I say this because my oncology team acknowledged that I do probably have Richter's transformation, based on the clinical presentation of a rapidly growing local node area while the leukemia seems to be under control elsewhere (other nodes OK, marrow improving) and increased blood levels of LDH (I finally stopped denying this possibility and actually inquired as to my blood levels of said biomarker).

For friends and family who don't want to wade through a lot of the technical stuff I posted below, see this excellent summary for layfolk of the condition by a CLL expert, Dr Sharman. This summary does not however tell the story like the following dismal graphic (click to enlarge fo easier viewing) from a large series of Richter's patients:

(note very little differences between whole group and those treated in fall off of survival)

What follows in this post is more science for those interested; I do it to keep my head straight. But I may not have much time left on this planet now and need to get right spiritually and emotionally. I plan a future post on this as have given this much thought of late....

Most all of the transformations in Richter's are to diffuse large B-cell lymphoma (DLBCL). Rarely there can be Hodgkin's lymphoma, accelerated CLL or prolymphocytic transformation.  For me there is no evidence for the latter 2 conditions, and I guess biopsy is the only way to rule out the odd Hodgkin's, probably also the response to chemo selected.

Looking over recent reviews on this condition, my future is definitely uncertain, the survival rate is not good for most of those who develop Richter's, the 80% of that come from what is called clonal evolution of one's CLL cells, by repeated mutation, a very bad one being a mutated p53, which is a tumor suppressor (read more here, warning quite technical) when it is normal, otherwise, with many types of mutations, the tumors go wild...

In the other 20% the DLBCL develops de novo as a secondary cancer. See an image which explains the different types (ignore the verbiage re mutated IgG status, too technical for this discussion, but if you are game this image is from this article)

The difference in prognosis between these two types of transformation is significant. In one recent article the median survival for those with de novo lymphoma was reported to be 62.5 months vs 14.2 months in those with clonal transformation. Unfortunately there is no commonly used clinically available test to differentiate the two types.

So what about treatment, then? Standard of care seems to be CHOP=R which if reasonably successful can be followed by stem cell transplant. Here is a summary from a state of the art article on CLL:

Management of Richter’s  syndrome  therefore  remains  unsatisfactory with overall response rates of around 34% using CHOP or platinum containing chemotherapy, and 47% using rituximab-containing regimen. The mean overall survival is around 8 months from end of treatment

Here are more survival curves from a large MD Anderson series:

Using a score derived from patient and tumor characteristics, from what I can tell I score a 3, see this dismal curve:

A little  better prognosis in Richter's was reported at ASH 2011 by a European group, with 15 patients treated with CHOP-R in a Phase 2 truak, there was a 67% overall response rate, a 15 month median progression-free survival and a 27 month  median overall survival


and this one looks better for those who respond to chemo and get transplant, albeit just 7 patients:

So time will tell, issues to be discussed with my onco team in the coming weeks include the following: do I need a biopsy to definitely prove diagnosis, how many cycles of CHOP-R, should we continue to pursue the viability of transplant with the two possible unrelated donors that were found on the registry match t.and again what about my trying CAR-T if the cells can be found to express CD19 and they can grow sufficient T cells?

Some links to pdfs of key Richter's articles, including a recent review and an earlier publication of  the MD Anderson experience:

Jain, O'Brien, 2012. Richter's Transformation in Chronic Lymphocytic Leukemia [most current review]

Tsimberidou, et al 2006.  Clinical Outcomes and Prognostic Factors in Patients
With Richter’s Syndrome Treated With Chemotherapy or Chemoimmunotherapy With or Without Stem-Cell Transplantation [MD Anderson experience]


Rossi et al , 2011. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation [all about p53 and survival differences]

Probably more to come when I find them....need to do this medical-intellectual exercise as I put off really thinking about my demise....