Now what?

[cheri]

Hi all~
I've been postponing writing this because I am so perplexed, and have been a little discouraged lately........but here goes.......
I have heard conflicting reports about which is harder to treat...de novo or secondary....the latest is that we think the MDS was there, had just switched to AML when discovered....( I had blood work due to recurring vertigo issues and major bruising was evident)
Induction Chemo put AML into remission, but underlying MDS resurfaced. I am not a candidate for BMT/SCT....Last BMB Jan 2011 indicated no AML had resurfaced...

After 8 months of Vidaza, no appreciable results...(or did it keep AML at bay?)I can't resume because my counts are too low lately.....
Still~
Get CBC 2xweek
Platelet dependent--transfused 1/week
Blood Dependent--transfused every 2 weeks
Exjade: 1500 mg daily/ ferratin levels dropped 200/month--last 3 months and are now around 1300....(Dr swears that it doesn't affect WBC/Plt counts)
Supporting drugs like Neupogen and Aranesp when needed @ weekly Dr visits

Previous to last (Thurs 6/16) CBC WBC 1.2, Hg 8.8, Plt 17***
***All of these numbers are scarily close to when I was first diagnosed in Oct 2009 with AML

Last Platelets transfused Friday 6/17 : Post cbc--Bump to 90k!--highest ever! (A+ cells, my type--seems to matter; B platelets give worst results)
CBC Yesterday (Mon 6/20): WBC 1.3; Hg 9.0; Plt 49-
-pattern seems to be that I lose approx 10,000 platlets/day--I don't have symptoms of bruising until they are in the teens--never had major bleeding issues, thankfully!

I am anxious because my Dr seems confused as well and wants to do another BMB tomorrow...my last one was in January. I know that is the right thing before moving forward, but where to next? I don't have 5q- (or didn't last time--could that change?)
I honestly don't have a clear understanding of all of the particulars of this disease, as many of you do......I read and read and not all of it makes sense. The more I read, the more I wonder if there could be other forces at work, like low copper, or low B-12 or who knows what?
I don't have a copy of my lst BMB results...Dr just said I was low risk....should I get a copy of this one in the hopes that at least YOU all can help me decipher it?

So where to next? Revlimid? If I can get it at all? Other testing? (Got my copper tested, no results yet).... Dacogen?
Reduce/discontinue Exjade? I'm so confused and have been feeling overwhelmed about where to go from here--I look and feel pretty good, otherwise, which is why this is all frustrating--how can I be this sick, and it doesn't show? Just a little tired...It seems all I am doing all week is living between blood tests, drs' appts, and transfusions.........And I have noticed a lot of short term memory lapses recently....names/conversations... chemo fog?
I asked my Dr to contact Dr Alan List, @ Moffit in Tampa Fla....he seems to be the MDS expert...anyone ever seen him? Will he extend a professional courtesy to consult with my Dr? I can't even travel to see him at this point....
Any insight would be much appreciated....thanks....

[Greg H]

Hey Cheri!

This disease is consistently perplexing and discouraging,which is why it's so great to have this forum with folks like you in it -- so we can all learn from each other.

I'm sure other folks are going to chime in who know more than I do, but I had a couple of thoughts looking at your questions:

Originally Posted by cheri

I have heard conflicting reports about which is harder to treat...de novo or secondary....the latest is that we think the MDS was there, had just switched to AML when discovered....( I had blood work due to recurring vertigo issues and major bruising was evident)
Induction Chemo put AML into remission, but underlying MDS resurfaced. I am not a candidate for BMT/SCT....Last BMB Jan 2011 indicated no AML had resurfaced...

Everything I have read indicates that secondary MDS is tougher to treat, but I'm not sure that you have secondary MDS. That's generally used to describe MDS that crops up a few years after chemo or radiation therapy for some other condition. Since AML and MDS are kind of linked, I don't think your bout of AML is really "some other condition." It sounds like it's all kind of the same bone marrow failure, just sometimes better and sometimes worse, with different names applied to it. (On the other hand, if you had radiation or chemo from something else a few years ago and I am forgetting it, maybe you do have secondary MDS. I recall that you have been through the wringer.)

Originally Posted by cheri

After 8 months of Vidaza, no appreciable results...(or did it keep AML at bay?)I can't resume because my counts are too low lately.....
. . .
I am anxious because my Dr seems confused as well and wants to do another BMB tomorrow...my last one was in January. I know that is the right thing before moving forward, but where to next? I don't have 5q- (or didn't last time--could that change?)
. . .
I don't have a copy of my lst BMB results...Dr just said I was low risk....should I get a copy of this one in the hopes that at least YOU all can help me decipher it?

So where to next? Revlimid? If I can get it at all? Other testing? (Got my copper tested, no results yet).... Dacogen?

The BMB is definitely a good idea, because that will tell you the blast count and rule out progression to AML. I try to get a copy of everything, and we can certainly help you interpret your BMB results. It's definitely possible for new chromosomal abnormalities to crop up.

Some folks have responded to Dacogen after Vidaza didn't work, though, if you can't take Vidaza right now because of your counts, Dacogen may not be an option either. There are drugs being tested in combination with Vidaza, as well as some new drugs in the pipeline, like Estybon.

I think your thought that you need a consult with one of the top MDS docs -- like Dr. List -- is an excellent idea. There are folks much closer to you than Florida, however. There's Azra Raza and Lewis Silverman in NYC, the folks at Johns Hopkins, and the folks at NIH in MD. Neil often points folks to this list of the MDS Centers of Excellence. I see a couple of docs in Philly on there. I'm not familiar with them, but others may have experience with Dr. Besa or Dr. Luger.

If I were in your shoes, I'd book an appointment with one of these experts. Since Vidaza doesn't seem to be working, and a BMB is out, a clinical trial may be your best bet, and the experts are going to have more knowledge of what's out there. The folks at NIH have been great about working with my local doc, and he was happy to draw on their expertise.

Take care!

Greg

[Neil Cuadra]

Originally Posted by cheri

Induction Chemo put AML into remission, but underlying MDS resurfaced.

Originally Posted by Greg H

Everything I have read indicates that secondary MDS is tougher to treat, but I'm not sure that you have secondary MDS. That's generally used to describe MDS that crops up a few years after chemo or radiation therapy for some other condition.

Disease classifications are a bit arbitrary. That doesn't mean that doctors and researchers aren't rigorous, just that they have to pick cutoff points to organize patient data into groups. If a patient has 19% blasts and certain other blood and marrow characteristics, they'll be told it's MDS Refractory Anemia with Excess Blasts. If the same same patient has 20% blasts the next day they'd be told it's AML. So I think Greg is right and that your bone marrow failure isn't two diseases taking turns, but one condition changing over time.

Data shows that secondary MDS typically shows up about five to seven years following chemotherapy or radiation. That doesn't fit your history. But knowing what's easier to treat or harder to treat is a matter of statistics over a larger number of patients. What matters is finding the best treatment for you as things stand right now.

If your doctor can consult with Dr. List I think it would be very useful. And if not Dr. List there are other MDS experts around the country. Many are mentioned in these forums. Another way to identify some of them is to look at the speakers on the agendas of the AA&MDSIF regional conferences.

[DanL]

There are a number of conflicting articles out there about which is harder to cure - primary or secondary mds or aml. Just this morning I read several articles (dates are important) that have started performing analyses that separate out the different variables.

Bottom line here is that most of the recent work done suggests that it really comes back to number and type of chromosomal abnormalities and overall health status (existing comorbidities). Whether it is primary or secondary or therapy related seems to be less relevant to the outcome. The historical context is that T-MDS/AML or S-MDS/AML patients typically have more or worse chromosomal abnormalities than deNovo.

I hope that helps, and good luck on the next steps, keep pushing for a good answer.

[Birgitta-A]

Hi cheri,
Hope that you didn't have any problems with the BMB!

Dr Alan List is a very wellknown expert - very good if your dr can contact him.

You know Exjade can give low WBCs and platelets though that is not common - I was never able to take more than 500 mg Exjade/day due to low WBCs.

Only about 25% of the patients without the 5q- chromosome aberration respond to Revlimid but some patients are responding during many years. Look ar Kirby Stones personal profile. He has a wonderful dr who never gives in.

May 2010 I received 2 units of PRBCs every week, my dysfunctional platelets were 22 and I took Neupogen 2 inj/week for my low WBCs. My ferritin was 5600 though I had Desferal and a low dose of Exjade. Then I accepted Thalidomide. I have not got any txs since Sept 2010. My platelets are about 100. The ferritin level is 1000. I still need Neupogen 2 inj/week (since neutropenic fever 2007). I can only hope that Thalidomide will continue to work for me.

Kind regards
Birgitta-A
Thalidomide á 50 mg 4 caps/week, Prednisone 5 mg/day and Neupogen 2 inj/week

[cheri]

Hi Fellas! Thanks for your responses! If I hadn't heard from Neil and Greg H, I would assume I was a goner!
Since I live alone, it is comforting to have input from other people, even if it is conversational. Although I have had a fighting mentality, I can get in a funk now and then because this disease is SO random and ridiculous! And is totally interfering with my social life/camping adventures!

Well, my CBC today, priorto bone marrow biopsy was :
WBC 1.3 (post bmb neupogen for 3 days)
Hg 7.2--HUGE DROP since 9.0 Monday
Platelets 28 (true to my 10k/day usual.........)
So it's off for 2 units of blood, 1 platelets tomorrow.....Bring the laptop, stack of bills, and camp out for the day!

Dr is putting a STAT order (rare) for BMB results and running the full gamut of testing......we'll just have to wait and see what transpires....I have an appointment Tuesday....
He does a great BMB though--very gentle and virtually painless......
He's a good guy/Dr and really cares for his patients. He promises to call in the experts once we get a read on the results.......TJUH didn't want to have anything to do with me after I checked out..UPenn just said "What TJUH said" Really? Thanks!
All along, I have been getting conversational second opinions from Hemo Dr's I have met along the way at conferences and such, but that is when I was still on the Vidaza....it may be time to venture out but Philly is not the answer for me.....anyone who says BMT is the only way is not for me...
So, having an old friend visit from Calif for a few days which will help me keep my mind off things....
Thanks, as always!

[cheri]

Ahhhh Birgitta!
My day is complete--you are the 3rd side of my triangle of hopeful information and inspiration! (figuring out this mess I'm in)
(I was hoping you'd reply, and we must have been typing at the same time....) I do appreciate EVERYONE's responses though! And it is crazy how many of us are on the same train but in different cars!

Yes, today's BMB was quick and easy, thanks for asking...the Xanax didn't hurt, either!

What actually, is the difference between Thalidomide and Revlimid? And what about side effects? (clearly, I'm post menopausal)
I am going to take all the information I can glean about alternative tx's like yours with me for the next appointment. ..your #'s seem very similar to mine, and you are doing great! And I'll refresh myself with Kirby's story..

Of course, my biggest fear is that the AML has returned, but either way, I'm still here and ready to continue the fight! See, I'm feeling better already--thanks to you all!

[Greg H]

Originally Posted by DanL

Whether it is primary or secondary or therapy related seems to be less relevant to the outcome. The historical context is that T-MDS/AML or S-MDS/AML patients typically have more or worse chromosomal abnormalities than deNovo.
.

Hey Dan!
Good stuff. I need to do some reading up on this. What you are finding makes perfect sense, when you think about it.
Take care!
Greg

[Birgitta-A]

Hi cheri,
Good that the BMB was OK !

Both Thalidomide and Revlimid work in many ways and most of them are probably still not known yet. Thalidomide is much older and cheeper.

Thalidomide can give neuropathy - damage the nerves often to the feet. Revlimid is much, much stronger. Both can give low counts initially and should be combined with Prednisone the first 3 months (I have asked my dr if I could continue with 5 mg/day). My WBCs decreased from Thalidomide - that is why I only take 4 caps á 50 mg/week instead of 50 mg/day. Thalidomide can give constirpation and Revlimid diarrhea.

Here is info about the way they work.
They inhibit the cytokines
1. tumour necrosis factor-alpha (TNF-alpha) (we have too much)
2. interleukins (IL) 1-beta, 6, 12, and
3. granulocyte macrophage-colony stimulating factor (GM-CSF)
They costimulate
4. primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity.
They are
5. anti-angiogenic (prevent new blood vessels to tumor cells)
6. anti-proliferative, and
7. pro-apoptotic (increase programmed cell death)
http://www.ncbi.nlm.nih.gov/pubmed?t...armendia%2C%20
Kind regards
Birgitta-A

[cheri]

Thanks Birgitta~
The details in the medical jargon...this is where I get lost and need my doctor to decipher what is right for me....(I appreciate the fact that you cite certain website pages that he could access if he should choose.........he is always impressed with the info I bring that I glean from Marrowforums...)

Now, am I having a flashback or did Dr Alan List have something to do with the introduction of Revlimid?

One thing that complicates my life right now is the inablity to travel to any major cities/clinical trials, because my #'s are so low.....and boy, am I STILL trying to untangle the insurance billing messes from my road trip to Florida this past winter!!!!!!!

[Greg H]

Hey Cheri & Birgitta!

I'm following this discussion with great interest, and really appreciate Birgitta'a summary of the various effects of thalidomide.

Birgitta, have you run across any studies that suggest which MDS patients might be most likely to respond to treatment with thalidomide? Or is that question -- like with the use of immunosuppressants -- still being worked out?

Take care!

Greg

[cheri]

Hi Greg
Birgitta is truly a wealth of information--I am always amazed at her scope of knowledge...
I, on the other hand, am here solely for comic relief!

[Birgitta-A]

Hi cheri and Greg,
When they started to use Thalidomide for MDS they gave the poor patients very high doses – up to 1000 mg/day . Of cause the patients couldn’t tolerate that and very few improved.

Now they look at the doses that have been OK for patients with the disease Myelofibrosis – that is 50 mg/day + Prednisone 30 mg/day tapered during 3 months.

Here they report 10 studies where 8 to 59 % of the patients improved:
http://online.haematologica.org/EHA1...se&-recid=3370

I have found abstracts for 6 of these studies. Here is info about the study with the best results:
http://onlinelibrary.wiley.com/doi/1...817.x/abstract
Kind regards
Birgitta-A

[cheri]

Thanks Birgitta....
I couldn't access the first link...

How does prednisone affect blood counts? I remember they put me on it in the very beginning when I was first diagnosed with AML, and not sure why they did. But boy, did I get lots of stuff done!

[DanL]

Prednisone affects several different systems, but in this role, it is suspected to help cell apoptosis (cell death), particularly in poorly performing cells. It also can have the impact of increasing platelet production within the marrow, so it may help offset some of the troughs experienced when on a treatment like thalidomide.

[Chirley]

Hi,

I was wondering about the use of prednisone too. A couple of years ago I had a transfusion reaction and was put on prednisone. My blood counts a couple of days later looked really good. I was boasting to my doctor that I must be getting better because my neutrophils had increased. He kind of huffed loudly and said that the prednisone was marginalising my white cells and that it was a transient response caused by prednisone. He explained that marginalising meant that the marrow was sending all it's reserves into the blood stream. He acted as if I should have known this. Well, duh!! I didn't. But I won't forget it.

Regards

[DanL]

the marginalizing is a process by which white cells that normally stick to the walls of blood vessels come free, thus the temporary nature of th wbc increase. prednisone is also used in tamping down inflammation or other reactions by muting immune respnse.

[Chirley]

Hi DanL,

So it's nothing to do with the bone marrow releasing the WC reserves? And I thought I learnt something! Damn doctors, just kidding.

Regards

[Birgitta-A]

Hi cheri,
Here is the abstract about Thalidomide from European Hematology Association Conference 2009:
EHA 2009 THALIDOMIDE FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES: A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE PUBLISHED STUDIES
Musto, Pellegrino, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero In Vulture, Italy

Background
Thalidomide has been used to improve the cytopenia of myelodysplastic syndromes (MDS). However, due to the heterogeneity of patient populations treated and of doses/schedules adopted in the different studies so far performed, the efficacy of this drug in MDS remains controversial.

Furthermore, some concerns also exist about its tolerability. Indeed, no individual clinical trial has been sufficiently extensive to provide a basis for a decision model to use thalidomide in MDS.

MethodsIn order to define better the role of thalidomide in MDS, we performed a systematic review of all published articles on this topic by using a Pub-Med web-site methodology.

Ten phase I-II studies, including a total of 527 MDS patients who had received thalidomide as single agent, were identified and examined. Neither phase III trials, nor previous meta-analyses were found.

Results Thalidomide doses widely varied in the different studies, ranging from 50 to 1000 mg/d. The response criteria also were not uniform.

Overall, average response rate was 32% (range 9-56%) and 43% (range 16-88%) on intention-to-treat analysis or considering only patients able to receive the drug for 12-16 weeks, respectively.

The large majority of responses were erythroid in nature (mostly resulting in transfusion-independence) and were achieved within 2-3 months, without a clear evidence of a dose-response effect.

Responses were more frequently observed in patients with lower IPSS risk score and with a recent diagnosis at treatment (< 1 year). There was no evidence of a correlation between response to thalidomide and baseline levels of endogenous erythropoietin, transfusion support or prior treatment with epoetins.

Cytogenetic response or changes in marrow morphology were only occasionally reported. The duration of response was highly variable, ranging from three months to more than six years. Side effects, mainly peripheral neuropathy, sedation, constipation, and skin rash, were frequent, determining a very high and often early drop-out (mean 44%, range 15-67%), even in responders and especially in elderly patients where thalidomide doses > 200 mg/d were employed.

Despite the fact that no thrombotic prophylaxis was generally adopted, thrombotic events were very rare and exclusively associated with higher doses of the drug. Two studies suggested a possible survival benefit for MDS patients treated with thalidomide.

Conclusions Based on available evidences, thalidomide remains a possible therapeutic option for selected MDS patients, if appropriately employed and managed. An early use of individualized doses, starting with 100 mg/d and increasing the dose up to no more than 200 mg/d, if well tolerated, is recommended for at least 12 weeks.

Lower doses may be enough in elderly subjects or for maintaining response. Preferable targets appear to be lower risk patients with transfusion-dependent anemia as single cytopenia, who are not candidates for alternative approaches, such as epoetins (high levels of endogenous erythropoietin or prior resistance), lenalidomide (no evidence of the 5q- cytogenetic abnormality) and high dose chemotherapy or hypomethylating agents (no blast excess). The detailed results of the meta-analysis will be presented at the Meeting

Kind regards
Birgitta-A

[cheri]

I just got word that I have transitioned to back to AML with blasts of 30-35%...
Not a surprise really, but so quick (since Jan) and scary nonetheless......nearing the end of the ride, I suppose......

ANY ideas where to go now, besides more induction chemo/bmt?

Have any of you been able to keep those #'s steady with any type of drug? ISeems to me at I've seen #'s of 50% reduced posted somewhere here, unless that was something else. Hope springs eternal, but I am not going to be chasing snake oil salesmen...
Sorry for the request of repeat info...I will be asking about Thalidomide and Revlimid, but just wondering and not sure what my little community center can do for me, when certain drugs are not AML approved....
To look at me, you'd never know..........
Thanks in advance for whatever guidance you have....cheri

[DanL]

Cheri,

Very sorry to hear about the recent setback.

Two treatments for relapsed AML are high dose cytarabine and G-CSF (CLAG) and etoposide, cytarabine and mitoxantrone (MEC). Another idea is to get checked for PDGFR to see if Gleevec is an option.

In addition to the above, there are many phase 2 clinical trials that you might be able to participate in that may provide more suitable alternatives for you.

[Greg H]

Cheri,

Good advice from Dan on this one. Have you trolled around on clinicaltrials.gov to see what's out there that might appeal to you?

I think I recall you saying at some point that transplant isn't an option for you, and I know you've been through the wringer with therapies. Is transplant not an option because you've taken it off the table or did someone else take it off the table for you?

Looking at age alone, it would certainly seem to be an option.

Take care!

Greg

[cheri]

Thanks DanL and Greg
Well, I don't see anything on clinical trials.gov relating to AML without the prior transplant.

I have taken transplant off the table for a variety of reasons....after much thought and research. (no sib donors) And I am not up to being poisoned to near death again with a strong induction regimen......for 2 months more at most....

Vidaza didn't work, and now my WBC, Pla and Hgb isn't drug friendly....
My Doc said being a little guy he can't access some drugs (Thalidomide), so I'm not opposed to going to a bigger institution in PA or NJ if I have help getting there....insurance limits my choices....Doc said NO! to Promatca....Revlimid not indicated for AML....

Not sure what the acronym to qualify for Gleevac is, DanL...can you clarify please? And what are those other 2--I had high dose Ara C and Danorubicin, (I think ) "3/7" at TJUH in Philly.....

Tomorrows CBC will tell alot as to how fast things are progressing.....

[DanL]

PDGFR is Platelet Derived Growth Factor and sometimes shows up in MDS and AML and can be responsive to Gleevec.

[Birgitta-A]

Hi cheri,
Did your dr suggest a new drug?

When I look at clinicaltrials.gov for patients with AML in New Jersey recruiting new patients I find a study of the Onconova drug Estybon (nr 29). At least one patient from this forum has participated in an Estybon study.
http://www.eventure-online.com/event...ongressId=4634

If you have the possibility for a SCT you could always get cord blood if they don’t find a donor.
Kind regards
Birgitta-A