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[Nadia T]

Hello everyone. I'm new to this forum and glad to have found you all.
I am 64 and was diagnosed with hypocellular MDS this summer. My red and white cells and platelets are all low thought the platelets are the lowest (11,000-20,000). I haven't needed a transfusion yet though will have one soon prior to oral surgery I need. I'm also fortunate in that I have few symptoms other than bruising -- I'm grateful every day for that. I went to NIH in November and was accepted into the trial for Campath. If I do that, it will be in January. Though I'm leaning that way, I'm still undecided and wonder if Watch and Wait is not still the better option right now. If any of you have input on this, I'd love to hear it! BTW, I was blown away by NIH. It is an amazing place and I felt extremely cared about and was encouraged to ask as many questions as I had.

I am sending best wishes out to you all as you cope with these challenges.

[Dick S]

Sounds like if you have all three lines down, you have some type of multilinial dysplasia same as I have. I have extreme fatigue from it, which you don't seem to have. I envy you. I'm still in a watch and wait situation. If it wasn't bothering you as you say, I wouldn't do anything right now because you may not like the inconvenience and side affects from the chemo. Just some thoughts and I am not a doctor nor I play one on TV.

[Neil Cuadra]

Nadia,

I'm surprised you haven't had a transfusion yet with platelets that low. What are your other counts like?

Were you diagnosed after a bone marrow biopsy? Assuming so, did the doctor explain what your biopsy results were? Do you know what MDS subtype you fall into?

As Dick says, "Watch and wait" might be fine for now -- some people live normally with fairly low counts -- but if your counts stay dangerously low and you start requiring regular transfusions then it's not a great long-term plan. You could use the time to solicit other second opinions.

The NIH is very organized and the doctors very attentive (I was impressed too!) but their goal is research so there's a built-in bias toward trials. For some trials they want patients who have not had previous treatments, in other words people like you. What does your own hematologist say about having you take Campath under a trial vs. taking the already approved meds: Vidaza, Dacogen, or Revlimid, and about those vs. watch and wait?

Did the NIH give you information about the tradeoffs involved in choosing a clinical trial? You can also read Clinical Trials: Are They Right For You? How hard would it be for you logistically since you live on the other side of the U.S.?

[Hopeful]

Hi Nadia,

Do you have any cytogenetic abnormalities? Do you have significant dysplasia? Did NIH give you a diagnosis of MDS vs Aplastic Anemia?

Besides Campath, you may want to look at ATG. It is my understanding that this has a higher success rate for immune mediated bone marrow failure. Some also consider it less risky because your lymphocytes aren't knocked out as long.

If you are interested in a second opinion that isn't biased toward the clinical trial, I recommend Dr. Paquette at UCLA - just a quick SW flight away.

[Greg H]

Hey Nadia!

I did the Campath trial at NIH. It didn't work for me (or, more precisely, it probably did produce a response, until abnormally short telomeres caused a relapse). Others on marrowforums have done it with success.

Neil's point about an institutional bias toward clinical trials at NIH may be correct, though that's not the vibe I've gotten from the folks I worked with there, who all seemed pretty genuinely concerned with figuring out what would be the best therapy for my particular case.

Besides, with a platelet count as low as yours, I'd be pretty wary of Revlimid, Vidaza, or Dacogen, because they are all quite likely to knock your platelets down even further, at least temporarily. (Of course, Campath will probably cause a temporary dip in all your counts as well. I'm not sure whether ATG does the same; maybe Hopeful can fill us in on that.)

But a lot depends on your diagnosis. If you are low-risk or INT-1 (which it sounds like is the case), neither Vidaza nor Dacogen makes much sense, because they work best in higher risk patients with excess blasts. If you are higher risk and have excess blasts, on the other hand, those would make more sense.

If you are deletion 5q, you definitely want to consider Revlimid, because the response rate is very, very high. If you're not deletion 5q, you've got a 25-30% chance of response (and will have to either do a trial or get approval for an off-label use).

If you have hypocellular marrow and a couple of the other indicators that suggest a higher probability of response to immunosuppression (HLA-DR15+, PNH clone, Trisomy 8), I'm not sure why you'd try Revlimid (a shot in the dark) instead of immunosuppression.

I'd definitely go with Campath before I'd go with ATG (My opinion based on a lot of study, but I'm not a doc, and your mileage may vary). Hopeful is right that Campath will knock your lymphocytes down more thoroughly, but, as a result, you won't need to follow it up with cyclosporine, which, based on my reading here, appears to have a lot of nasty side effects and "weaning" or "tapering" issues. Unless you have a job or vocation that exposes you to a bunch of viruses, the risk of infection post-Campath is pretty well taken care of by the Valtrex and Pentamidine treatments. ATG by itself is not nearly as effective as ATG plus cyclosporine, and, for MDS, I'd do the Campath instead of that combo. (AA is a different story; the NIH hasn't had much luck with Campath for AA.)

I hope you won't think we are all a bunch of busybodies asking about your counts and BMB results; but we've all been down this road, and we know that the devil is in the details with this disease. Because, in fact, MDS is not a disease, but a bunch of diseases clustered together, and the details are what tell you which of those variants you are most likely to have. And the holy grail of MDS research is figuring out how to tease apart all this different kinds of MDS and figure out how to treat them.

If you have any questions at all about the details of what it's like to participate in the Campath trial, feel free to give me a shout here, in a PM, or off-list.

Take care!

Greg

[Hopeful]

Hi Nadia,

I agree with Greg that immune suppression vs. the other MDS drugs may make more sense for you right now in hopes of putting the disease into a longer remission.

However, I would go with ATG/Cyclosporine before Campath. So we have a debate on our hands! From what I've read, Campath seems equivalent in response to Rabbit ALG/Cyclosporine, which doesn't appear to be as effective as a first line of treatment for immune mediated diseases. Now if you have blasts or cytogenetic abnormalities that are leading to the MDS diagnosis, that's a whole other story. But if your MDS diagnosis is only due to significant dysplasia in your cell lines, there is a chance that it will behave like AA.

ATG/Cyclosporine will bring down all of your counts for a few days because of the high fevers that you will spike during the administration at the hospital. However, once the fever subsides, your counts will return to your "normal" (or potentially even higher). Then the waiting begins...

Also, although some people have a bad reaction to Cyclosporine, most people don't, especially if the doctors are skilled in administering it. There are a lot of kidney transplant patients that are on the drug for life! Also, Cyclosporine is used in clinical trials after relapse from Campath. It is a strong drug. It is a dangerous drug. It is a powerful drug as well. I owe my life to it.

Finally, I don't think the relapse rate is any better with Campath vs ATG.

This is just my opinion on the issue. Of course, I'm biased on the issue I certainly don't want to discourage people from the clinical trial. I just don't see Campath as the "silver bullet" for MDS or AA. For this reason, it would be my second choice.

[Greg H]

Hi Nadia & Hopeful!

Hopeful makes a passionate defense of ATG/CsA vs. Campath based on her own success with the former. Given that Campath failed to fix my own problem, I'm not sure I can be quite as passionate.

I can, however, offer some data. Dr. Elaine Sloand's team at NIH published a study of IST in MDS in the Journal of Clinical Oncology in 2008 that, among other things, established the superiority of the ATG/CsA combo over either drug used alone. Of the 129 patients treated, 30% responded. Among those who got both ATG & Cyclosporine, the response rate was 45%.

Among INT-1 patients who got both drugs, response rate was 54%.

The same team mounted a trial of Campath in MDS patients and reported in JCO last November a response rate of 77% among INT-1 patients.

So, let's look at the scoreboard for the best responders, the INT-1 patients:

ATG+CSA - 54%
Campath - 77%

Looks like a clear win for Campath, no?

Well, not really. You see, the response rate you get depends on the patients you start out with. If you can narrow down the folks who are most likely to respond, and only let them in the trial, you are going to get better numbers than if you take a broader range of patients.

The 2008 paper on ATG+CSA is based on a much wider set of patients. Sloand and her team used what they learned in that study to create a filter for the Campath study, accepting only patients who had a strong probability of response. So, the Campath response rate would have been higher, even if it only worked as well at ATG+CSA. Using data from the earlier study, their regression model predicted that INT-1 patients under 60 with HLA-DR15+ had a 67% probability of response to ATG/CSA -- not far off from what they got with Campath.

Hopeful's impression that Campath for MDS has an inferior response rate is not supported by the data. The data suggest, instead, that Campath is equal to ATG/CSA. As far as I know, the November 2010 JCO paper by Sloand's group at NIH is the only paper out there on Campath for MDS, but it could be that Hopeful has data from another one that we need to include in our deliberations.

There was another NIH trial of Campath for relapsed Severe Aplastic Anemia that got poor results (although not for one marrowforums member), but that's a different disease and a very, very different set of patients -- who had already relapsed once.

There can be some degree of overlap between MDS and AA -- or, maybe, some uncertainty about which diagnosis applies in a particular individual. Hopeful's signature suggests just such a case, and my newly-discovered TERT mutation may be another. But I think it would be a mistake to assume that all hypo-MDS is the same as AA.

Both of Sloand's studies on IST specifically excluded folks who had a prior diagnosis of AA -- and that means the results might not apply to folks sitting firmly on the AA-MDS fence.

I don't really think, at this point, we know whether ATG/CSA or Campath is better; they seem pretty comparable. Sloand's paper says she decided to give Campath a go because of the nephrotoxicity of cyclosporine -- that is, it's hard on the kidneys. And there's the whole issue of how you taper it correctly, which seems to get talked about a good bit here on marrowforums.

So, what's a patient to do?

Try to learn as much as you can about the options, understand the response rates and how well those correspond to your individual disease profile, take a look at the side effects and other potential downsides, pay your money, and take your choice.

I have copies of both the JCO studies I referenced here (as well as the summary of the poster presentation on the SAA Campath study from ASH last year) and would be happy to send them via email.

Take care!

Greg

[Nadia T]

Thanks all. You make such good points about the numbers etc. I agree that the Campath trial might owe its success rate to who they let in. My leaning towards it is because it DOES have a decent response rate with people like me and it seems less toxic.

But all this might be moot now. I got a call from NIH today saying that my last BMB showed a chromosome abnormality in one of 20 cells they studied --is this del(5q)? They want me to get another BMB to recheck before I come for the treatment.

They also told me that if I do the campath, I would be getting it subcutaneously instead of by infusion, which means no hospital stay (I'm embarrassed to admit I kinda was looking forward to being coddled inside NIH)

The doctor mentioned revlimid as the tx if more cells show the abnormality. What do you all know about that?

I appreciate you so much -- and I don't mind questions at all. I just don't always have the answers. A bit more info is that my cellularity is 20% and my blasts were <5%

[Nadia T]

Greg -- I forgot to ask you: what's been the next chapter after campath? Has there been anything else suggested or are you in the midst of some other medication?

[Greg H]

Hey Nadia!

I'm glad the Great Debate that Hopeful and I indulged in was of some use. I, too, went for the Campath after a lot of the pins fell into place (Trisomy 8, HLA-DR15, normocellular marrow rather than hypercellular, under 60). Those same pins, of course, also predict response to ATG/CsA.

Interesting that the Campath protocol is now using subcutaneous injections. I hadn't heard about that. Is this still Clinical Trial NCT00217594? In my case, the first couple of doses of Campath (including the initial 1mg trial) produced violent rigors. After that, the worst thing was the Benedryl they gave me before the injections. It was actually a little ridiculous to be using up bedspace -- though the NIH Clinical Center bedspace was certainly cheaper than trying to stay in a Bethesda hotel for two weeks. Yikes!

Will you do inpatient for a couple of days, then outpatient?

So, they found one cell with deletion 5q? If so, you are in fact likely to get a recommendation to try Revlimid. You might ask that your upcoming BMB include FISH for deletion 5q. FISH uses 200 cells and might give a better sense of whether the one out of 20 they found in the karotype analysis is just a fluke.

20% cellularity is pretty darned low for MDS; generally MDS folks are mostly hypercellular. But I'm guessing you must have significant dysplasia in your cell lines if you've been diagnosed as MDS instead of AA.

As for me, post-Campath, I have entered the NIH trial of Danazol for folks with tiny telomeres and TERT or TERC mutations. I wrote about it in October here and plan an update shortly (but have to get a newspaper on the street first). Other folks are in the same trial.

The general feeling amongst the docs at NIH is that I in fact responded to the Campath -- my counts went up, including in particular my reticulocytes -- but then I crashed. Relapse is apparently a common problem for folks with too short telomeres.

Keep us posted on your progress, and don't hesitate to ask any questions that come up.

Take care!

Greg

[Nadia T]

FSH was the one test not done (or should I say, tests)? Actually I'm not terribly dysplastic so I'm not at all sure why the diagnosis was MDS, but all the docs at NIH concurred (as did the doctors at Seattle Cancer Care Alliance)

Those folks are amazing and I may zoom up there for another BMB in the next week so I could keep my date with NIH if necessary. When will you be there?

Also, what is Trisomy 8? I haven't heard that term anywhere.

Be well, Greg. Thanks for answering my questions.

Nadia

[Greg H]

Hey Nadia!

FISH is good at spotting abnormalities that might not show up in the 20 cells they manually examine for karotype. For example, my Trisomy 8 showed up in FISH before it did in karotype. So, if you had only one del5q out of 20, it might be nice to have FISH on that. It's pretty common to do an MDS panel that includes Chromosomes 5, 7, 8 and maybe some others.

Trisomy 8 is an abnormality pretty common in MDS. It means you have three copies of Chromosome 8, instead of the usual two. There's some debate about whether it's good, bad or mediocre. There are also monosomies -- like the dreaded Monosomy 7. That means you only have one copy of the chromosome, and having only one copy of 7 has an unfavorable prognosis.

Del5(q) or 5q- means the long arm of chromosome 5 is missing. It has a favorable prognosis, because about two-thirds of folks with that abnormality respond to Revlimid. The tricky thing about Revlimid for you is that it tends to initially knock down your platelets, and yours are already pretty low.

I was at NIH last week, collected my Danazol, and am back home. I return in May for follow up.

Take care!

Greg

[alyse]

Hi:

If anyone wants to read about the Campath trial, I have submitted an exhaustive narrative of my experience at NIH in August 2010 which should be somewhere on this site. I have AA not MDS so I do not know if my experience applies here. I was in a trial for relapsed and refractory A.A. patients. It appears to be the identical treatment for MDS.

After my diagnosis in Nov. 2008, I had ATG/Cyclosporine at NY Presbyterian Hospital in New York City. I had a rapid, terrific response in terms of blood cell counts, but I felt miserably sick for nearly six months after treatment. I also relapsed within a month of being taken off cyclosporine (I was on it for 13 months). Following my relapse, I was transfusion dependent (platelets and red) for more than six months.

Compared with the reactions I had to ATG (including returning to the hospital for four days of high dose steriods due to serum sickness which caused a rash over my entire body; and a fungus in my esophagus which made me nauseated for months),Campath was like getting a virus for a few days. Also being at NIH was an amazing experience. (Again, see my report on the experience.) It did take longer for Campath to kick in but it was worth it.

Today, 15 months post treatment my hemoglobin is 12.5; white is 2.9; platelets are 100,000 and neutrophils are 1780. I am going to Vietnam and Cambodia in February on vacation. I know how lucky I am and I am extremely thankful that I had the opportunity to have Campath rather than another round of ATG. Of course, I fear relapse every day but try not to dwell on it.

Good luck no matter what treatment (or non treatment) you choose. My only suggestion to you is not to fear Campath if the wise doctors at NIH recommend it.

[Lisa Z]

Wow, sounds like a great trip coming up!! We are thinking about Israel in July; part of a tour group.
Glad your counts are all good.
Mine seem to be holding their own as well. I return to NIH in March for my 3 year follow up. Wow, time has gone by fast and many wonderful things have happened in my life!
Will anyone else be down there around that time, who is participating on the Campath trial?
Who ever thought one would say, "I'm looking forward to my BMB?" I just hope I have someone who can perform this procedure well. My last one was torture!
Wishing everyone on the forum a HEALTHY and happy New Year!