Unmutated IGHV

[Jim-Boy]

Morning all,

just completed D15 on cycle 1 on V & O few Bumps in the road, but getting through well pretty well,

I have been looking back on recent comms from my Dr who advised on letter I have Unmutated IGHV: IGHV3-48*03, 100% germline homology, I haven’t discussed yet as now between Drs as current one has moved on, also on the letter not but discussed is splenomegaly with infarct, I could do the Google thing but if anyone has any advice on these it would be appreciated,

On the whole we are seeing some very good results thus far from the treatment

thanks all

[Zweistein]

IGHV3-48*03 is decoded as follows:

Locus: IGH

Gene type: V (variable)

Subgroup: 3

Gene position: 48

Allele (variant): 03

This is the gene within the IGHV region that is actually used in your CLL cells.

And 100% germline means that there is no difference/mutation in comparison to your normal genes.

imgt.org/IMGTScientificChar...

en.wikipedia.org/wiki/V(D)J...

[Jim-Boy in reply to Zweistein]

Thankyou, for my simple mind, your last point as being there is no difference/mutation can I take that as a good thing?

[Skyshark in reply to Jim-Boy]

Unfortunately no, IgHV unmutated is an indicator for earlier need for treatment, a rapid and good response to treatment with novel drugs but also earlier progression and need for re-treatment.

[Jim-Boy in reply to Skyshark]

thanks

[Zweistein in reply to Jim-Boy]

The so-called somatic hypermutation of IGHV is part of the healthy maturation process of B lymphocytes. Immature B lymphocytes with unmutated IGHV as CLL cells are considered to be more dynamic in their development. In the light of new therapies, the IGHV mutation status is regarded as less important than formerly.

[BigfootT]

Jim-Boy, This may help. If you look at the chart in the upper right. 3-48 has an incidence of about 0.8% of Unmutated. Fairly rare. I have a rare unmutated finding as well. My specialist couldn't draw any conclusions or prognostics from it. The concerning finding is 4-39 which tends to have a higher incidence of Richters in unmutated, Trisomy12 patients. I believe they call that Subset 8 patients. Thankfully you don't have that!ashpublications.org/view-la...

Bigfoot

[Jim-Boy in reply to BigfootT]

Thanks for insight, much appreciated

[Stamphappy in reply to BigfootT]

Bigfoot, I am 3-38 *3. I don't understand what subset I fit into idk . Can you explain that, please?

[BigfootT in reply to Stamphappy]

I'm sorry, but I can't. It seems to me there are so many possibilities that you just may fall in the "other" category. I'm a novice here, but I think some IGHV mutations are seen frequently and fall into these subsets (much like 17p, Tri12, 13Q and 11Q do with chromosomes) while many others are seen much less frequently. My takeaway, when I briefly asked my doctor about this, is there is far more they don't know about our CLL cell biology than what they do know and how these mutations impact our progression/prognostics is a bit of a mystery.

Bigfoot

[Stamphappy in reply to BigfootT]

Thank you for trying to answer my question, Bigfoot T. Perplexing. I haven't found any articles addressing 3-38 *3. It sounds like you have a nice doctor. Best wishes.

[Spark_Plug]

I was told When I asked about my unmutated status, "It just means you won't have chemo".

Keep in mind some of the conflicting answers are because not all locations treat the same way. The U. S. is more relaxed to use newer drugs, other countries may still use chemo as a first required treatment before they will go to another therapy. So, it follows that if chemo does not perform well with some types of CLL it may be reflected in what a doctor mentions as your prognosis. The boundaries are being refined as to how treatment will turn out.

[genla]

My husband was on W&W for 14 years and is unmutated, so mileage may vary. He is also a very conscientious daily vitamin D consumer, not sure if that had anything to do with it or not.

[Jim-Boy in reply to genla]

thank you - that is very reassuring - I have a good supply of vit D - perhaps i should follow suit

[dumbsaintmind in reply to Jim-Boy]

Vitamin D has been shown in multiple studies to prolong TTFT (time to first treatment). Many CLL patients present with a deficiency at diagnosis so it should be protocol at this point to test levels and prescribe megadoses of D if needed.

My vitamin D level has bounced between 50-70, which many studies are now showing may decrease risk of certain cancers and all cause mortality.

Word of advice: if you do end up taking Vitamin D, make sure you take its cofactors (Vitamin K, unless you eat lots of leafy greens) and (magnesium which helps vitamins D to be used in the body).