End to watch and wait?

[DanL]

So I have been on the non-regimen of watch and wait for almost exactly 2 years. My doctor told me that I would probably know when it was time to begin treatment, and I think that I am there. Last week's CBC came out at:

WBC 4.8
Neutrophils 3.5 - 73%
Lymphocytes 24%
HGB - 12.3
HCT 38
PLT 20

Complicating factors - Trisomy 8, grade 2+ to 3+ reticulin fibrosis.

This is the first time my HGB has dropped below 13.5, though I don't really notice any impact - i did walk almost 7 miles yesterday without rest during or after the walk..... it is also the lowest my platelets have been. If somebody looks at me funny I bruise these days. WBCs have been pretty steady.

We have found 3 potential 10/10 donors, and my sister is a 9/10 match. I am considering beginning treatment with vidaza or dacogen to start and then moving to transplant.

My concerns focus on the marrow fibrosis and that i have found very few studies that determine if vidaza or dacogen improve marrow fibrosis, whereas revlimid and thalidomide, and even danazol have at least anecdotal references to improving marrow fibrosis.

Any thoughts? Am I too concerned about the fibrosis part of this equation? I know that collagen fibrosis is considered worse than reticulin fibrosis when it comes to transplant outcomes.

Thanks.

[Birgitta-A]

Hi Dan,
Your counts are really very good except for the platelets. As you know almost all drugs can decrease platelets.

Vidaza has showed quite positive results in several studies of patients with trisomy 8 but all groups are small and need confirmation: https://ash.confex.com/ash/2009/webp...aper23003.html

You seem to know much about fibrosis already. I have not been able to find any studies about the impact of for example Vidaza on regression of fibrosis but here is an abstract about response to Vidaza in patients with MDS with marrow fibrosis. The overall response rate was 63% that is quite good compared with other patient groups.
http://meeting.ascopubs.org/cgi/cont.../18_suppl/7089
Kind regards
Birgitta-A

[tytd]

Hi Dan,
You seem to have a lot of factors in your favor including your young age, good performance status, lack of anemia and no need for transfusion. These might appear to outweigh the negative factors of fibrosis and low platelet as long as you are not having significant bleeding. You still must be in the IPSS intermediate risk category which might mean you should not jump to transplant too soon. On the other hand, I realize that the low platelets are a poor prognostic factor and it is hard to live with the restrictions they entail -- but I wondered what the pace or trend in your platelet drop has been and how well the platelets you have function??
I too get scared when they hit 19 or 20k, (something about that number seems worse than 21k.) My own experience, which I realize is unique, has been one of a very slow platelet decline. I have fluctuated between 16k to 22k over the past 2 years. I know that it is such a difficult decision about when to start treatment or go to transplant and I would seek several different expert opinions as I bet you have already done. Have you thought about a Promacta trial or Vidaza + Promacta trial? Good Luck tytd

[DanL]

TYTD, I really appreciate the response and thoughts. my platelets have been between 21k and 29k for most of the last 2 years. I had a brief stint at 90k while taking prednisone, undergoing treatment with rituxan and taking azathioprine, but came down with PCP which caused me to drop it all at once, especially in light of the change in diagnosis from ITP to MDS.

What concerned me is the sudden drop in HGB from 13.5, which has been very steady down to 12.3, which while not substantial in terms of anemia, appears to be a change worthy of noting.

As for the bleeding, I seem to clot well when i am cut, but when i bruise, it is fairly ugly. if i hit myself relatively hard, it spreads to about 4 inches. I do have some amicar to help out if i get too concerned, but have not had to use it.

I have had consultations with three different groups including the city of hope and two of them said to wait until further progression, the other was in favor of immediate treatment. I decided to hold off in the absence of symptoms. I was concerned about the promacta trial because of the ITP trial information that showed several patients developing marrow fibrosis after being on promacta for a period of time - it was reversible in most cases though. I have not really considered the vidaza plus promacta. It definitely sounds like an interesting choice if they are willing to accept patients with moderate to severe fibrosis like i have.

Birgitta, as always i appreciate your insight. I have noticed that you seem to do well on thalidomide - have you had any bone marrow biopsies to determine whether you still have fibrosis or not? Has the severity lessened?

[Hopeful]

Hi DanL,

I am curious why your doctors are not suggesting trying IST first. You are young and have a trisomy 8 mutation (which is seen in immune-mediated MDS). Your counts are continuing a steady decline. So, why not use this time to see if something like Cyclosporine alone could reverse the trend? Cyclosporine is well tolerated and you could see results in 2-3 months.

I also had reticulin fibrosis +2 and an MDS RCMD diagnosis when things were at there worst. When the immune attack was controlled, the fibrosis eventually resolved as well. Reticulin fibrosis is reversible. Callogen fibrosis is not. As this article points out, reticulin fibrosis shows little correlation with the severity of the disease.

http://www.haematologica.org/content/96/2/180.full

This article talks about the benefits of IST for the treatment of MDS with trisomy 8.

http://bloodjournal.hematologylibrar.../841.full.html

If I were in your shoes, I would talk do my doctor about trying cyclosporine alone during this watch-and-wait period to prevent further damage to your marrow and potentially reverse the disease. Vidaza just doesn't make sense to me. It also isn't a long term solution. IST can be.

[Hopeful]

Originally Posted by DanL

We have found 3 potential 10/10 donors, and my sister is a 9/10 match. I am considering beginning treatment with vidaza or dacogen to start and then moving to transplant.
Thanks.

There was a time when I wondered why my doctors weren't pushing for a transplant. My disease was rapidly progressing, and I also had sibling matches. It was discouraged because my doctors see people die and have life altering GVHD from transplants. I now share their opinion that you should never rush a transplant for MDS if you have other options. Having matches is not enough reason to take this risk.

[Birgitta-A]

Hi Dan,
My dr has not yet discussed a BMB to evaluate the effect of Thalidomide on the fibrosis. I have been satisfied with the good counts and that the blast cells have decreased from 0.1 to 0 in my blood.

In one of the first reports about Promacta for MDS patients they report that neither peripheral nor BM blast counts had increased but they didn’t mention fibrosis that has been reported from trials with ITP patients.
https://www.eventure-online.com/even...ongressId=5650
Kind regards
Birgitta-A