mds-fellows plus trisomy 8

[celebrations]

Hi +8-fellows,

I have been following all the mds-discussions with great interest and I really appreciate the comments based on professional knowledge here.

Since the 5q-people is a very special group among the MDS, luckily responding to Revlimid with a big probability, I wanted to ask what's about special therapies and special experiences for the +8s?

I am treated in an MDS-execellence-center in Germany. The head of my MDS-team is an internationally known professor of cytogenetics.
He's also published on +8, giving it a rather poor prognosis.
All I have read about MDS it seems that cytogenetics influence the course of this wicked disease a big deal.

I have been surviving some of my professor's prognosis already being in my 6th year of MDS, first RARS, then RCMD (all blood-lines affected).

With EPO and then thereafter Valproic acid I had some transient response, they both made be transfusion independent for a couple of months.
Currently I am tx-dependent every 15 days.
Watch&Wait for a SCT somewhere in the future if my liver and kidney counts will still permit.
I am on Exjade and I am 54.

If there are some +8s here on this forum - I know there are - I would be delighted to read your cyto-comment.
What do you know about +8 ? Do your doctors talk about it as an aspect of certain therapies, e.g. ATG...

I will be probably starting a clinical trial with Revlimid, because there also could be a response for +8s...

I' d highly appreciate your answers,

Thank you very much,
Bergit

[DanL]

Bergit,

I am also a sole +8 MDS. A lot of the research that has been done over the years has the nasty habit of including +8 with other cytogenetic abnormalities and then creating a prognosis on this basis. This is also done frequently with AML. A small handful of researches in the US have been hypothesizing recently that +8 cells don't necessarily mean poor prognosis. An example is that treatment with ATG on +8 patients expands the size of the +8 clone, but also seems to improve symptoms in many of them.

When measured alone, recent studies indicate that +8 has been confirmed as an intermediate status for both AML and MDS. When combined with other cytogenetic changes, there is a worse prognosis.

A couple of studies regarding Vidaza and the experimental drug Estybon have both shown favorable characteristics in Trisomy 8 patients, but these are both very small studies. Overall, there really isn't as much research done on +8 as there has been on monosomy 7 del 5q.

Cheers
Dan

[Greg H]

Hey Bergit!

I'm +8 but also have dup1(q21q31). In my case, it seems as though the Chromosome 1 abnormality preceded the +8, since there was no +8 at all in my initial cytogenetics and it appeared only in FISH. But it appeared in the karyotype in later BMB results.

The late Dr. Elaine Sloand at the US National Institutes of Health used +8 for a good bit of her research on the use of immunosuppression in treating MDS. Looking retrospectively at a large group of MDSers treated with ATG, Cylosporine, or both, she found that +8 was one of the indicators of probably response to immunosuppression.

She then did laboratory research that proved the presence of +8 often results in the development of a special cadre of T-cells programmed to attack +8 bone marrow progenitor cells. That supported the notion that some patients could be helped by suppressing T-cells and cutting off the attack. The idea is not that all +8 folks will respond to immunosuppression -- or that only +8 folks will respond. But it is an indicator for more likely response to this kind of therapy.

There is evidently some new research out there that suggests +8 has gotten a bad rap over time and is actually not as negative an indicator as once thought. I hope to track some of this data down and will share it when I have it.

Take care!

Greg

[Neil Cuadra]

Greg,

Whether or not trisomy 8 deserves the bad reputation, it's advantageous that it's been researched because doctors know more about what treatment approaches are most likely to pay off for the +8 patients.

In a way it's like the choice of MDS or AML. AML may be even more dangerous than MDS but has the advantage of a ton of research across a large number of patients.

But given a choice we'd still all rather have "none of the above".

[celebrations]

Dan, Greg and Neil,
thankx so far, I am always eager to know about new trials and new results of research. Europe has been always behind the States.

Revlimid is only licensed for MM not yet for MDS.
Campath and other new drugs are not even on a trial-level.

I know ATG, they sucessfully administer it to a lot of the AA-patients in Germany. When I was offered an ATG-therapy a couple of years ago, I was too gutless to try. Although I especially was adressed as a +8-candidate, where a immunesuppression might work. Later I read your bone marrow should be hypocellular for this therapy, mine is hypercellular (only two letters can make the difference here !!! :wink Anyway one of my doctors was pro the other was aganist, so I went with the one who had serious doubts. Maybe a mistake.
Anyway you are standardly given ATG before a transplant, mhh...

Dan or Greg, has anybody of you tried Revlimid to become transfusion-independent? Any suggestions of your physicians?
The options for +8s are limited!
Experimental drugs, orphan-drugs are rare, insurances do not pay and the treating physician has to take the risk of side-effects.

Greg, Dan? Is a SCT an option for you?

Read you again,
Bergit

[DanL]

Bergit,

i have not had any mds specific treatments. my original diagnosis (pre bone marrow biopsy) was itp, so i was treated with prednisone (no impact), 8 cycles of rituxan (no obvious response), and then with azathioprine. i seemed to be responding to the azathioprine as my platelets got all the way up to 100k which they have not been at any point before or after. problem is that i got PCP pneumonia and was taken off of everything.

my red counts are solid, white counts are solid, but my platelets hang out at around 30k week after week - for a little over 1 year now. i have not received any transfusions.


I do think that immunosuppression may be a viable option for me, but ultimately, i know that transplant is where this must go. i am trying to hold off a few more years to give the procedure more time to improve results. there are some very exciting trials that originated out of germany using treosulfan for conditioning with excellent results....we are now seeing confirmation trials in the us.

[Greg H]

Hey Bergit!

Like Dan, I figure there's a transplant out there for me at some point, but I'm also trying to hold that off for a while.

I spoke with my local Hematologist last week about options if the IST doesn't work for me and we talked a bit about Revlimid. He's very familiar with the drug because it's used for multiple myeloma, and said it was generally well tolerated by his patients -- that is, the side effects aren't too bad, in his experience. It only works for about quarter of non-5q folks overall, as I understand it. But it seems to work a bit better in folks who have mostly red cell problems.

I might be likely to try it if the IST doesn't work and my transfusion interval becomes intolerable. Even though my doc has had good success with Vidaza, I wouldn't do that unless I progressed to high-risk and was ready for transplant. My transplant doc (assuming I stay with the same one) likes to use Vidaza pre-transplant to try to get rid of the cytogenetic abnormalities before starting the chemo.

She also discouraged me from doing ATG, because it's used in the SCT process. That's one of the reasons I was interested in the Campath trial. While a number of studies have found hypocellular marrow to be an indicator for a response to IST, NIH's research has not. They find the key factors are age (under 60 years) and the presence of the HLA-DR15 allele. So it might be worth a shot if you have DR15, despite the hypercellular marrow. Mine is normocellular.

I'm currently a non-responder to Campath, so I'm certainly not a cheerleader for it. But one of the other things that makes it attractive compared to ATG is that ATG works best when followed up with cyclosporine, and that drug brings with it a lot of issues. Campath knocks down the T-Cells longer and more completely than ATG, making it possible to avoid cyclosporine. On the other hand, the trial I am in can offer cyclosporine to folks who have responded and then relapsed.

Catch you later!

Greg

[Greg H]

Originally Posted by Neil Cuadra

In a way it's like the choice of MDS or AML. AML may be even more dangerous than MDS but has the advantage of a ton of research across a large number of patients.

Neil,

Excellent point. I noted in the articles surrounding that recently published study of gene mutations in MDS that one doc said that MDS research is seven years behind AML research in that regard.

The great thing is that there is so much super research being done on MDS now.

Thanks!

Greg

[celebrations]

Hi Greg,

with this I see that you are about on the same level of information as I am:

I spoke with my local Hematologist last week about options if the IST doesn't work for me and we talked a bit about Revlimid. He's very familiar with the drug because it's used for multiple myeloma, and said it was generally well tolerated by his patients -- that is, the side effects aren't too bad, in his experience. It only works for about quarter of non-5q folks overall, as I understand it. But it seems to work a bit better in folks who have mostly red cell problems.

I might be likely to try it if the IST doesn't work and my transfusion interval becomes intolerable. Even though my doc has had good success with Vidaza, I wouldn't do that unless I progressed to high-risk and was ready for transplant. My transplant doc (assuming I stay with the same one) likes to use Vidaza pre-transplant to try to get rid of the cytogenetic abnormalities before starting the chemo.


Thank you very much for your post about IST.
What' s about the side-effects of Campath, do you have any, or do you tolerate well. How long will your physician go on with the therapy, because there is not yet a real success, as far as I understand.
In my archive I had some data that +8s responded in an american trial with Revlimid (30 patients) with 11% [alltogether, means all non-5qs, had a responding rate of approx. 25%]. So 11% is rather low....but as I wrote, I probably will try. I have my first appointment to that next week.
Also in Germany Vidaza is used for high-riskers and as a pre-transplant therapy. They still call me "low-risk".
There'll be a BMP on August 1st to confirm, I hope.

Tomorrow I will catch some blood, although my HGB might not be around 8,5 yet. But I need it for QOL and travelling for two weeks. So I will have to discuss that point again (I already have several times), because transfusion regulations only want to transfuse under 8...Transfusionmanagement is always a big subject for me and other MDS-patients.
What experiences do you have about that?

Greets,
Bergit

[Greg H]

Originally Posted by celebrations

What' s about the side-effects of Campath, do you have any, or do you tolerate well. How long will your physician go on with the therapy, because there is not yet a real success, as far as I understand.

Hi Bergit!

The trial of Campath that I am enrolled in involves an intravenous infusion of 10mg per day over ten days (preceded by a 1mg test infusion). I was hospitalized for that period (though, frankly, the last week could have been outpatient). The infusion reaction involves fever and shakes for the first couple of doses, then no side effects.

In the months after taking the drug there have been no severe side effects. All of my blood counts were depressed for a couple of months before beginning to rise again. My lymphocytes are still below normal, so I take Valtrex (Valacyclovir) to prevent viral infection and a monthly inhaled dose of Pentamidine to prevent PCP pneumonia. When my neutrophil count was below 500, I also took Ciprofloxacin to prevent bacterial and fungal infection. But my ANC is above 1000 now, so I no longer need that antibiotic.

Unless there is some significant worsening of my blood counts or transfusion interval, I will wait until November to see if the Campath works. That will be nearly 12 months.

There is another trial of Campath in the US -- at MD Anderson in Houston -- that involves the same dose I had (10mg per day over ten days) but repeats this every 28 days for up to six months.

Originally Posted by celebrations

In my archive I had some data that +8s responded in an american trial with Revlimid (30 patients) with 11% [alltogether, means all non-5qs, had a responding rate of approx. 25%]. So 11% is rather low....

If you have a copy of that study, I would enjoy seeing it.

Originally Posted by celebrations

Tomorrow I will catch some blood, although my HGB might not be around 8,5 yet. But I need it for QOL and travelling for two weeks. So I will have to discuss that point again (I already have several times), because transfusion regulations only want to transfuse under 8...Transfusionmanagement is always a big subject for me and other MDS-patients. What experiences do you have about that?

HGB under 8.0 seems to be the rule of thumb at my local hospital. But my hematologist is generally quite willing to transfuse at higher than that (8.3 or 8.5) if I am symptomatic (feeling fatigued, heart flutters, that sort of thing). The folks at the National Institutes of Health have told me they use 8.0 as a general guideline for younger patients, but use 9.0 for patients over 60.

So far, my health insurance company has never questioned any of my transfusion requirements.

Good luck with your upcoming BMB!

Take care!

Greg