Slow increase in lymphocyte count in the years after V&O

[MGirl-Aust]

I was wondering if others had experienced a slow increase in lymphocyte count in the years following V&O therapy? I’m worried the CLL is slowly relapsing, but my haematologist says I shouldn’t worry and that it may be due to slow recovery of the lymphocytes after treatment. I don’t have any new symptoms/signs or other lab test changes. I reached uMRD at end of treatment but has not been measured since then.

Completed V&O in March 2022.

Lymphocyte counts are as follows:

Nov 2022: 1.1

Nov 2023: 1.25

June 2024: 1.65

Jan 2025: 1.85

Thanks, Michelle

[AussieNeil Partner Administrator]

Your haematologist could well be correct - your lymphocyte count is still well within the normal range. If this is really worrying you, ask for an immunophenotype test, which lists the absolute lymphocyte count by type, as well as the number of clonal B cells.

Neil

[MGirl-Aust in reply to AussieNeil]

Thanks Neil, will consider asking for that if it continues to rise.

[Skyshark]

A cytogenetic test may detect MBL, quite likely "low count" MBL, less than 0.5x10^9/L. As CLL is defined by a clonal cell population 10 times that, greater than 5x10^9/L, I think your lymphs will have to be about 7 before a diagnosis of CLL progression could be given.

V+O is not a cure, CLL returns and needs re-treating. The question is "how fast" and "how soon". Your complex karyotype may indicate a reduced time to next treatment but your ALC at 33/34 months from end of treatment remains enviably low.

Conversion from uMRD to detectable MRD starts from the end of treatment. Retaining uMRD4 at 5 years from end of treatment is unlikely, about 10%. At 30 months from end of treatment 36% of those that had reached uMRD4 were still uMRD4.

For IgHV unmutated without TP53 aberrations CLL14 median time to detection of progression is 66 months from start of treatment (55 months from end of treatment).

CLL14 at 6 years 35% had started next treatment, 39 out the 67 that had progressive disease.

I'm about a year behind you and very much hoping that re-treatment with V+O is approved by the time I need re-treatment. The ReVenG trial for V+O after V+O will start yielding results around 2027 with completion 2029. At present only the US allows re-treatment.

CLL14 steady decline in uMRD from end of treatment.

[ShoulderCat in reply to Skyshark]

Hi Skyshark,

Any idea what H-MRD and L-MRD stand for?

Thanks.

Michael

[Skyshark in reply to ShoulderCat]

H-MRD is High measurable residual disease, >=100 cells per 10,000.

L-MRD is Low measurable residual disease, >=1 and <100 cells per 10,000.

pmc.ncbi.nlm.nih.gov/articl...

As it varies with the population of normal B-cells there isn't a fixed count of MRD that will indicate when H-MRD becomes Progressive Disease, or even High count MBL.

Eaxample

Patient A : CLL clonal population 5x10^9/L, ALC 7. MRD count = 7143.

Patient B: CLL clonal population 5x10^9, ALC 9. MRD count = 5555.

Patient C: CLL clonal population 3.88x10^9/L, ALC 7. MRD count = 5555.

A and B have progressive disease but quite different MRD counts. C does not have a large enough clonal population but has the same MRD count as B.

[ShoulderCat in reply to Skyshark]

Thanks. Very helpful. 👍

[MGirl-Aust in reply to Skyshark]

Thanks Skyshark. Just saw my haematologist and he said they could do further tests but if it is CLL slowly returning it would just worry me, and would not change management, so he advised not to. He still thinks my slowly increasing count is probably lymphocyte recovery after treatment. He said I’m unlikely to need further treatment for some years yet. In the past he has made it clear that it is definitely a case of when rather than if further treatment will be required.

I asked about retreatment with V&O and he said it is available on a trial in Australia at the moment (but obviously not necessary for me right now). It’ll be very interesting to see the results of the trials with retreatment of V&O (although the need for so many blood tests early on in treatment would put me off a bit!).

Hope your remission lasts for a long time!

[Poodle2]

I think I would trust your consultant. I was also treated with V+O, finished in June 2023. My lymphocytes are generally around 1.5-1.8, they bounce up and down but my September blood draw made me nervous as they were 2.1. This month they are back to 1.7. I think it's natural it worries us, I'm just like you but I think I would not worry at this point. Normal count is 1-4.8 I believe.

[MGirl-Aust in reply to Poodle2]

Thanks Poodle! It’s good to hear of similar experiences, and reassuring to know we’re alone in our worries 😊. All the best to you.