To Begin MDS Treatment? And with what?

[DanL]

I am new to the forum and have been through a bit of a ride over the past several months. I was originally diagnosed and treated for ITP - Platelets were 21k, RBC/WBC were normal. I went through high dose prednisone for about 6 months (including the weaning cycle), had 2 rounds of treatment with Rituxan, and was taking Imuran for about 3 months. In August I got PCP and began the Prednisone taper and quit taking Imuran. This timing also coincided with my highest platelet count since May - I was up to 96k and held steady for about 1 month. In the last two months I have dropped back down to the 30-45 range and held pretty steady.

Also in August, my diagnosis was changed to MDS with predominant Thrombocytopenia. I have mild dysplasia (<10%) in my RBC and WBC lines, trisomy 8, mildly hypercellular marrow - 70-80%. I have the inverted cd4/cd8 ratio as well. Recent BMB (12/18) showed no changes since the July BMB.

My doctor is pretty concerned about the low platelets and wants to begin treatment with Vidaza. Although I know that this is the first drug of choice and follows the NCCN guidelines, I can't help but to wonder whether immuno-suppressive drugs might be a better approach. Both seem to take 3-4 months to kick in....My basic internet research seems to suggest that immuno-suppression works well with Trisomy 8 low and intermediate risk, young patients.

Does anybody have any experience with this situation? Any suggestions on what to do? What to ask? Has anybody gone the immuno-suppression route first and then gone to Vidaza or is it typically done according to guidelines - Vidaza then on to immuno-suppressives?

I feel like I am pretty well researched at this point and should probably have a little more trust in the doctor, but want to get some feedback from the people whose lives are affected directly by the disease.

One last note, we have activated a search for a bone marrow donor - but given that I am IPSS-1, there is not a rush on the part of the BMT doctors to move forward.

Sorry for the long introduction. Any help out there?

Dan

[akita]

Hi Dan,

you wrote that you got PCP in Summer 2010.

This is one of the potential dangerous diseases i have to avoid in my actual immunosuppressed status after allogeneic stem cell transplantation. So i must take Ospen 1500 mg twice a day.

PCP can come when you are immunosuppressed. HIV-patients with CD4 counts <= 200 have to make a prophylaxis for PCP. Perhaps you have/had similiar values because of your Prednisone intake..?

What has happened to your PCP? Is is gone? Do you take medicaments for it?

Whats about your CD4/CD8 counts?

The status of your immunecompetency is important for the choice of your next therapy...

Nice regards,

Margarete

---
Margarete, 53, living in Vienna, Austria,
MDS/AML M2, aSZT 4/2008, chronic GVHD

[Hopeful]

Hi Dan,

I'd get another doctor/opinion involved, as I tend to agree with you...immune suppressant therapy can be very effective for MDS with a trisomy 8 mutation.

http://bloodjournal.hematologylibrar...hort/106/3/841

Since you are not transfusion dependent, cyclosporine alone (vs ATG) may be a viable less risky option. Follow Lisa V's threads for a good success story with a a similar situation.

Best of luck!

[DanL]

Magarete,

I assume that the PCP was from the combination of Rituxan, Prednisone, and Imuran. I was taking all 3 during the months of June, July and then the latter two in August.

After the doctors figured out that it was PCP, I took Bactrim for about 3 weeks and was better. I am fully recovered. The biggest problem there is that I think that I had the pneumonia for about 3 weeks before recognizing the problem. I went in a little bit naive about the potential for side effects from the various treatments, so I didn't really know what I was looking for......I do know better now.

Thanks and good luck with your recovery.

[lindy]

Hi Dan,

In August you were diagnosed with MDS after being ITP for several months.
How where you diagnosed with MDS when your RBC & WRC are normal?
What is PCP? Thanks for sharing.

Best wishes for your recovery.

[akita]

[quote=DanL;16262]

I assume that the PCP was from the combination of Rituxan, Prednisone, and Imuran. I was taking all 3 during the months of June, July and then the latter two in August.

Are you sure?

Prednisone can cause such infections when given for a too long time for augmenting the thrombocytopenia. Three months of intake are too long and there exists the danger of getting infections.. I have studied this yesterday and safed some studies related to this problem in my inbox. If you like, i can send you the links which perhaps are not so interesting for the whole forum...

But i don`t know about Rituxan and Imuran leading to infections (my lacking knowledge- perhaps they do in some cases)

When prednisone works, it usually leads to an early platelet response after a few days and should be tapered after ca. 4 weeks.

But maybe Prednisone did not help you, and instead Imuran let increase your platelets? You can try to analyze this looking in your blood-reports conbined with the times of intake of prednisone and Imuran. When did the platelets begin to rise? This knowledge could be helpful for you. You can see then, if you are responding to prednisone or not.

>After the doctors figured out that it was PCP, I took Bactrim for about 3 weeks and was better. I am fully recovered.

Why are you sure for that?

>The biggest problem there is that I think that I had the pneumonia for about 3 weeks before recognizing the problem. I went in a little bit naive about the potential for side effects from the various treatments, so I didn't really know what I was looking for......I do know better now.

This seems to be not a side effect, but an effect of too long intake in your constellation.

--

For your prognosis and treatment assessment it would be necessary to know your exact classification. Did the doctors classify you now as WHO - "MDS - unclassified" ? I m not so sure how the doctors in your case came to this classification and if the differentialdiagnosis could perhaps show another possible diagnosis.

Perhaps it would be useful to consult a mds-specialized hematologist for a second opinion. The treatment then could be different..

If you should be "MDS-unclassified", a special risk assessment should be made in estimating your prognosis. The scoring systems do not put MDS-unclassified in any risk-class and it is the estimation of the treating doctors to assess your risk-status, which can range from low up to higher risk classes.

Maybe your doctors did that before proposing Vidaza. Are you informed?

I absolutely cannot contribute much to that.

Your doctors have the exact results of your blood and bmb-parameters.

How high is your LDH? Do you show signs of fibrosis? .. and 100 more questions plus expertise from an experienced hematological team...

But i today will go to my hospital for my first phototherapy session for my slerodermiform GVHD. In the library they should have the fulltext of a study recently published, where different additional parameters are described, which can result in a poor diagnosis for some even low-risk MDS-Patients. If not somebody else has taken the journal from the shelf, i can copy the few pages and thake them home.

You can get title etc. of the study by going to http://pubmed.org , and then typing in 20573398

Regards,

Margarete

[Greg H]

Hey Dan!

Welcome to the forum! You have clearly read up on MDS and there's no reason I can see that you shouldn't be asking the question you are asking.

My situation is somewhat similar to yours in that I'm younger (54) and have INT-1 MDS with trisomy 8. But my problem is more in the red cell line than platelets (though my platelets are no great shakes, either.)

I'm currently enrolled in a clinical trial of the drug Campath, which is an alternative immunosuppressant therapy (to the usual ATG and cyclosporin routine). The trial I am in is at the National Institutes of Health in Maryland.

I did a long post about the theory underlying immunosuppression and MDS here. And I've been describing my experiences in the trial here.

The trial I am enrolled in is this one. They are still recruiting, and NIH has been the leader in trying immunosuppression for MDS. But, seeing you're out west, it might be worth checking out this new clinical trial at MD Anderson in Houston.

It's too early for me to have a success story with Campath yet, but at least one other member of the forum has experience with the NIH trial and has had good success.

If you are really interested in exploring immunosuppression, I'd encourage you to call on the NIH trial so you can talk with Dr. Matthew Olnes about your situation. He's a real straight shooter and the conversation will definitely be enlightening.

I'd be happy to email or talk with you offline about my experience -- or to have a conversation right here so everyone can participate.

Let me end by saying that my local doc initially wanted to treat my INT-1 MDS with Vidaza, but the data on its effectiveness among lower risk patients made me very skeptical, which is why I decided to go the immunosuppression route instead.

One final question: Do you know if you are HLA-DR15 positive? That's a good predictor for response to immunosuppression. But you may not have been HLA-typed if you're not considering transplant yet.

Take care, and good luck!

Greg

[DanL]

thank you for all of the responses. As you all know, there are just so many factors involved with MDS.

Lindy - my diagnosis is based on trisomy 8, hypercellular marrow, mild dysplasia in the red and white blood lines. PCP is a type of fungal pneumonia that happens to people with immune compromised systems. Most people can fight this off. You are particularly susceptible when you have a low CD4 count or a CD4/CD8 inversion.

Margarete, the diagnosis that I have been given falls under the newer WPSS classifications as either RT or RCMD, which have varying prognoses. The predominant issue seems to be the refractory thrombocytopenia. I was asking about continued immunosuppressive therapy on the basis of my lab results week over week. Imuran tends to take 3-4 months to kick in when it is used for ITP, and my numbers had just begun to shoot up (went from the mid 20s to mid 90s over about a 6 week period). Imuran does suppress the immune system as does Rituxan (wipes out b cells for about 6 months). About the prednisone - tell me about it....not only did it not really help - i have developed avascular necrosis in both hips as a result.....not fun.

Greg, I have been following your post with quite a bit of interest. I too have read that Vidaza really seems to have a great effect on patients that have increased blasts - i am less than 1%, and fall into the intermediate -2 and high risk category, which is part of what concerns me - not to mention the grade 3/4 thrombocytopenia when I am already at grade 3. As for the DR15, I have not received an answer on this one yet. I did have my blood drawn for potential donor matching and asked the question, but the doctor has been out and his assistant said that she doesn't read too much of the detail in the phenotypes, so I am not sure. It does seem to be a strong predictor of success for this type of treatment - although I have also seen studies showing that up to 70% of MDS Trisomy 8 patients respond to immunosuppressive agents......this could be due to a greater concentration of the DR15 in trisomy 8 maybe?

[Greg H]

Originally Posted by DanL

Greg, I have been following your post with quite a bit of interest. I too have read that Vidaza really seems to have a great effect on patients that have increased blasts - i am less than 1%, and fall into the intermediate -2 and high risk category, which is part of what concerns me - not to mention the grade 3/4 thrombocytopenia when I am already at grade 3. As for the DR15, I have not received an answer on this one yet. I did have my blood drawn for potential donor matching and asked the question, but the doctor has been out and his assistant said that she doesn't read too much of the detail in the phenotypes, so I am not sure. It does seem to be a strong predictor of success for this type of treatment - although I have also seen studies showing that up to 70% of MDS Trisomy 8 patients respond to immunosuppressive agents......this could be due to a greater concentration of the DR15 in trisomy 8 maybe?

Dan,
It just so happened that shortly after my local doc suggested Vidaza (we had already scheduled the insertion of a port-a-cath), I participated in an AAMDS webinar that featured either Dr. Sekeres or Dr. Steensma (I forget which). I had already discovered that all the studies used to win FDA approval for Vidaza showed effectiveness in high risk patients, not lower risk folks, so I asked the webinar doc about treating low-risk patients with the drug. He said only about 25% of lower risk patients respond to Vidaza and indicated he'd first look at Revlimid, immunosuppression, or watch & wait.

We watched and waited for six months, until my increasing Trisomy 8 percentage got my transplant doc all excited and, about the same time, I found out I was HLA-DR15+. That finding sealed the deal with my local doc on immunosuppression, a therapy he had been pretty skeptical of previously. his final comment was "If you're going to do IST, you ought to do it at NIH, because they're the experts."

I don't know about the coincidence of Trisomy 8 and HLA-DR15+. If you look at the protocol for the NIH Campath trial, they have a formula for probability of response that takes into account age, HLA-DR15 status, and total number of transfusions. Dr. Olnes told me the latter hasn't really proven all that powerful a predictor, with age and HLA-DR15 the key variables. Other studies have found other factors predictive of IST response, including the presence of a PNH clone, and a hypocellular marrow. I really don't know how IST jibes with your mostly thrombocytopenic problem, but I imagine Dr. Olnes would have some data on that.

IST doesn't work for everyone, clearly. I'm not even sure it's working for me yet. One thing I wonder about your case is whether, given the fact you managed to contract PCP, you've already been pretty darned immunosuppressed. How low did you lymphocytes get? Campath takes them to zero for a month or so and knocks down the CD4s for a lot longer than that.

Let me know if I can be of use. I've got a copy of the latest article on the Campath trial if you want it, as well as a nice summary on the whole IST for MDS deal, co-authored by the late Dr. Sloand of NIH. That one has some data pulled from various studies on factors that predict IST response.

Take care!

Greg

[akita]

Prednisone:

1. Consensus Report ITP Blood 2009

International consensus report on the investigation and management of primary immune thrombocytopenia

http://bloodjournal.hematologylibrar...full/115/2/168

Blood, 14 January 2010, Vol. 115, No. 2, pp. 168-186.

Citation:

Corticosteroid therapy. Corticosteroids are the standard initial treatment. Additionally, they may also reduce bleeding, independent of the platelet count rise by means of a direct effect on blood vessels.32,33 Unfortunately their adverse effects rapidly become apparent and create significant complications. With time, the detrimental effects of corticosteroids often outweigh their benefits. Prednisone is the standard initial first-line therapy for ITP patients.22,34,35 Prednisone is usually given at 0.5 to 2 mg/kg/d until the platelet count increases (≥ 30-50 x 109/L), which may require several days to several weeks.9,36,37 Although the treatment is effective, patients are at risk of developing corticosteroid-related complications that vary with the dose and duration. To avoid corticosteroid-related complications, prednisone should be rapidly tapered and usually stopped in responders, and especially in non-responders after 4 weeks.36,38

References:

36 Ben-Yehuda D, Gillis S, Eldor A. Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura. Israeli ITP Study Group. Acta Haematol. 1994;91(1):1–6.[Medline] [Order article via Infotrieve]

38 Pizzuto J, Ambriz R. Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American group on Hemostasis and Thrombosis. Blood. 1984;64(6):1179–1183.[Abstract/Free Full Text]


2. Pizzuto J, Ambriz R. Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American group on Hemostasis and Thrombosis.

http://bloodjournal.hematologylibrar...e2=tf_ipsecsha

Blood. 1984;64(6):1179–1183

Citation: page 5/6 freetext pdf you can download from right above:

Consequently, we recommend corticosteroids
as the initial treatment of choice, particularly
in cases of acute or subacute ITP where the PCR rate
is high. Moreover, the prolonged administration of
corticosteroids is not recommended, because a favorable
response, when it occurs, appears rapidly in one or
two weeks.

3,5

This recommendation is supported by the
data on 477 patients analyzed in this report, which
show that continuation ofcorticosteroids for more than
45 days does not produce an increased incidence of
PCR and only increases the possibility of undesirable
side effects.

2’5’7

References:

2. McMillan R: Chronic idiopathic thrombocytopenic purpura.
N Engl i Med 304:1 135, 1981
3. Karpatkin 5: Autoimmune thrombocytopenic purpura. Blood
56:329, 1980
5. Ambriz R, Conte G, Aviles A, Ortiz A, Sinco A, Morales PM,
Pizzuto i: ıCual es la secuencia terapeutica en Ia purpura trombocitopenica
idiopatica? Analisis en 138 casos. Rev Invest Clin 34:1 13,
1982
7. Gugliotta L, lsacchi G, Guarini A, Ciccone F, Motia MR,
Lattarini C, Lattarino C, Bachetti G, Mazzucconi MG, Baccarani
M, Mandelli F, Tura 5: Chronic idiopathic thrombocytopenic purpura
(ITP): Site ofplatelet sequestration and results of splenectomy.
A study of 197 patients. Scand i Haematol 26:407, 1981

---
Fsn,

Why was MDS not considered as a differentialdiagnosis for ITP? Did you get an initial BMB before diagnosis of ITP?

Asking,

with kind regards,

Margarete

[DanL]

Margarete,

Thank you for the research. How did your session go today?

I think that given my age and the low chance of MDS a BMB is not normally done unless you are not responsive to ITP therapy, which is what happened. Thrombocytopenia was my only symptom, there really wasn't any reason to believe it was anything more. After about 3 months of treatment, we did the BMB and then changed to the MDS diagnosis....

I can't really say why my doctor stayed with the steroids for so long. Due to the MDS diagnosis, we began tapering down from 80mg/day in August. I caught the PCP toward the end of the month when I was down to 20mg/day. I had to stay on for a while because of the PCP, finally stopped completely in October/November.

I actually feel the best that I have felt since May - i am currently not taking any medications - although I suspect that will be changing shortly.

[lindy]

>I think that given my age and the low chance of MDS a BMB is not normally done unless you are not responsive to ITP therapy, which is what happened. Thrombocytopenia was my only symptom, there really wasn't any reason to believe it was anything more. After about 3 months of treatment, we did the BMB and then changed to the MDS diagnosis....<


Dan, I can relate to that. My doctor said the same, due to my "young" age (I'm 53, what about you?) & thrombocytopenia is my only sympton, BMB was not done. But my mum had MDS/AML, still he thinks BMB is needed if there's a change in symptons or I'm a bit older. I'm wary & try to find out more about MDS in the meantime.

Now that you are feeling better, I hope your condition will stay that way. Good luck!

[DanL]

Lindy,

I am 36.

[akita]

>Thank you for the research. How did your session go today?

Oh, it was only a testing session, where they investigated what the optimum dosis for the UVA1 radiation would be. They tested different doses on different spots of my skin.

Today i will go again to the hospital, where the doctor will see the results of the test on my skin and then decide about the details of the therapy. If my skin would have proved to be more sensitive, i will get a lower dosis. I did not feel/experience any special events on my back/neck, where they did the test. Lets see. My dating will be at 1.15 pm..

>I think that given my age and the low chance of MDS a BMB is not normally done

I thought you were 36 (profile information). Why do you think your age matters?

>unless you are not responsive to ITP therapy, which is what happened.

The problem could be, that because of your prolongued prednisone therapy you have had already health problems and the choice of therapy would depend on the correct diagnosis. i can post you at least one study where it is indicated that if you have MDS and not ITP, prednisolone has not helped in the past. Per PM or officially?

>Thrombocytopenia was my only symptom, there really wasn't any reason to believe it was anything more.

...for you, but the doctors should have a more wider knowledge, could have considerating that you might have MDS instead and taken an informed consent by you, in which you decide, whether you want to get a BMB or not, risking an uncorrect diagnosis and treatment..

>I actually feel the best that I have felt since May - i am currently not taking any medications - although I suspect that will be changing shortly.

Thats wonderful... whats about a watch- and wait modus for the weeks till you have found an optimal treatment?

Did you have symptoms caused by your thrombocytopenia? Or was it a routine blood-counting in spring?

Regards,

Margarete

[akita]

Lindy and Dan,

sorry i did not read your recent postings before responding to Dans posting of yesterday..

What concerns the age i think a differential - diagnosis for MDs has to be done before starting an ITP-Therapy. In the Consensus Report ITP 2009 MDS is listed under the differentialdiagnoses.

----

See again:

International consensus report on the investigation and management of primary immune thrombocytopenia

http://bloodjournal.hematologylibrar...full/115/2/168.

---

The relatively young age for the onset of MDS - most people are older is a special risk factor. If you get MDS when you are young there could be special reasons for that and you might be in a situation of difficult/poor prognosis. E.G. in case it would come out that you have mutations or a secondary mds. in my case nobody came to the result that i should have an investigation for MDs, because my blood counts seemed to be normal for years before diagnosis. I had subtle changes in my peripheral blood accounts which would have been considered as relevant for further diagnosis if a hematologist would have seen me. So i experienced years of undiagnosed MDS and it was detected only as it was really late - after conversion to AML. i was very tired in these years, running from doctor to doctor for the correct diagnosis but i did not consider a blood desease.So i was diagnosed with sleep apnoe syndrome (for which also the differentialdiagnosis for anemias should have been made was was not done), made a rehabilitation cure for my asthma. My capability to work decreased and a had therefore financial problems which i otherwise would not have had. But i do not know which treatment they would have given to me if the MDS would have diagnosed earlier. The situation in the hematologic ward, where i got the polychemotherapies to prepare me for the SZT was under time-pressure and many risks i would not have experienced if the correct diagnosis would have been done earlier. For example it was not possible to me to find a matched donor in the short period before the necessary transplantation, my lady-donor was mismatched, and that caused a high probability of dangerous Graft-Versus-Host-desease. I got this and survived after having stayed in hospital after SZT for 10 months...I could report further details to this problem - complex...

So i vote for an early correct diagnosis for these blood deseases..

Regards,

Margarete

[Susan L]

I've got a copy of the latest article on the Campath trial if you want it, as well as a nice summary on the whole IST for MDS deal, co-authored by the late Dr. Sloand of NIH.

Greg - Did something happen to Dr Sloand?

[Neil Cuadra]

Originally Posted by Susan L

I've got a copy of the latest article on the Campath trial if you want it, as well as a nice summary on the whole IST for MDS deal, co-authored by the late Dr. Sloand of NIH.

Greg - Did something happen to Dr Sloand?

She died in early December. Greg posted about it here. From his post:

Originally Posted by Greg H

On a tragic note, Dr. Elaine Sloand, one of NIH's stalwarts on the MDS research front, died last week. Her husband died in early November. Though Dr. Olnes shared the news with me, he offered no details on cause of death. The staff was still visibly shaken by the loss of their colleague.

It is a great loss for the community of MDS sufferers as well. Though Dr. Sloand wasn't as visible in webinars and patient conferences as some other MDS experts, the work she was spearheading in the lab and in the clinic was breaking important new ground in teasing apart the strands of the tangle that is MDS.

Dr. Olnes said he and his colleagues planned to honor her memory by continuing her work. I wish them Godspeed in that effort.

[Susan L]

I am so sorry I did not read that posting about Dr Sloand. I am in shock - she was the BEST physician I ever had the opportunity to meet. The caring and personalism she gave was unbeliveable.

[tytd]

Hello Dan, Yours is a very puzzling case as are many of us. If it were not for the chromosomal abnormality(trisomy 8) in the bone marrow, I think that you would still be classified as ITP. It is strange that your bone marrow did not show significant dysplasia in your megakaryocytes since the thrombocytopenia is your main problem. I wonder if you could have had ITP and then developed treatment-related MDS from the Imuran. I certainly agree with Greg and others that you should try seeking another expert opinion and NIH is a good suggestion. Perhaps Nplate would be another possibility?? I am a fan of "watch and wait" if your platelets stay in a reasonable range, say greater than 30k without bleeding symptoms,(and if your risk of progression is considered low.) Although it does restrict your lifestyle somewhat to have such low platelets, I think you always have to weigh the risks of the treatment(Vidaza, ATG, Campath, BMT, Nplate) against the risk of bleeding from the low platelets. Have you had any bleeding or bruising symptoms from the low platelets? What is your hemoglobin and WBC? I have dealt with low platelets for almost 28 years but I have been lucky. I wish you good luck and hope you have the luxury of waiting longer before having to make a decision about treatment. TyTd

[DanL]

Tytd,

I am currently at 43k platelets, HGB 14.2, HCT 43, RBC 4.8, WBC 7900 (70% neutrophils, 20% lymphocytes - don't remember the others, but in the normal range). I have not had any transfusions. When I am At 40k platelets, I don't have any abnormal bruising. I don't have prolonged bleeding time - I am on the low end of normal, meaning that I clot pretty quickly. When I am in the 20s, the bruising gets pretty colorful.

The Imuran caused T-MDS is a curiosity - most of the cases I have seen involved long term use at an average of 5+ years - I ony took it for about 3 months. Possible, but probably unlikely? not sure. The articles I have read seem to focus on Monosomy 7, deletion 5q and 11q23 changes as therapy related MDS with Imuran, although I am sure there are exceptions.

How would we determine if risk of progression is relatively low? I just had my second BMB on 12/18 (first one was 7/15). No increase in blasts or dysplasia seen, but we are waiting on the genetics. First test had trisomy 8 in 20/20 metaphases reviewed.

Thanks again.

[Greg H]

Dan,

Tytd makes a great point about watch and wait.

That was the decision I made until a subsequent bone marrow showed cytogenetic changes -- i.e., I went from a Chromosome 1 abnormality in 55% of my cells and Trisomy 8 in 5% to both abnormalities in 55%. This got my transplant doc excited, because "the clone is evolving."

When I met with Dr. Olnes at NIH, he said going ahead with the Campath made sense, because immunosuppression tends to work best earlier in the disease, before the T-cell war starts to create additional chromosomal mutations. However, had I chosen not to go with IST, he said he would recommend continued watch and wait rather than Vidaza or transplant, given the relatively low impact of the disease on my quality of life (basically, an RBC transfusion every six months.)

So, watch and wait is definitely a viable strategy.

Good luck!

Greg

[Greg H]

Originally Posted by DanL

How would we determine if risk of progression is relatively low? I just had my second BMB on 12/18 (first one was 7/15). No increase in blasts or dysplasia seen, but we are waiting on the genetics. First test had trisomy 8 in 20/20 metaphases reviewed.

Dan,

This is really interesting. Essentially, your first BMB said that all your stem cells have the Trisomy 8 abnormality, yet you've got normal counts in all but the platelets. This fits with what I've heard from Dr. Sloand and Olnes at NIH, namely, that it's possible that Trisomy 8 cells, unmolested by t-cell attacks, may be able to make blood just fine, thank you very much.

I think the folks at NIH would be very interested in reviewing your case.

I'll be very curious to see what your new cytogenetics say; I hope you'll share them with us.

In answer to your question to Tytd, I'd reckon it would be a bad sign to seem more cytogenetic abnormalities cropping up, particularly something like monosomy 7, which we will hope does not happen.

Take care!

Greg

[akita]

Dan,
>The Imuran caused T-MDS is a curiosity - most of the cases I have seen involved long term use at an average of 5+ years - I only took it for about 3 months. Possible, but probably unlikely? not sure. The articles I have read seem to focus on Monosomy 7, deletion 5q and 11q23 changes as therapy related MDS with Imuran, although I am sure there are exceptions.

Maybe it is not even possible,because there exists a considerable latency from the start of the previous/MDS causing therapy to diagnosis for t-MDS. In your situation there was practically no latency.

In the following study the median latency was 96 in range from 7-775 months. Many cases were investigated in this study. So i suppose you could not get MDS in such a short period of intake of Imuran till BMB.

https://service.gmx.net/de/cgi/deref...F2402713a.html

The study concludes that special karyotypal changes can be brought in more or less close connection to specific treatments; And that the sole +8 is more common in de novo AML/MDS.

Not only t-MDS can be caused by certain therapies/medicaments, but also De-Novo disease can go together with chromosomal changes caused by "non-iatrogenic exposure".

"However, chromosome changes in de novo disease may well be associated with non-iatrogenic exposure. For example, an association between exposure to organic solvents and trisomy 8 in AML has recently been reported.60".

So it could be possible that another substance or influence contributed to/caused your MDS.

Kiind regards,

Margarete

[cathybee1]

Dan, I have read your post and the others which have given you excellent advice. I know very little about the substance of the decisions you are facing. But one thing I have learned in trying to get a diagnosis for Bruce's bone marrow disorder (still not conclusive) is that there is no substitute for an MDS Specialist for your second or third opinion.

Based on our personal experience, I think the suggestion that you contact a MDS expert is an excellent one.

We have a local hematologist and initially went to a big city University Medical Center hematologist (who is a bone cancer specialist but not a MDS Specialist).

After a long wait, we finally were able to see an MDS Specialist at UCLA, and he actually recommended a less aggressive course of treatment than the other hematologists. Consulting a doctor who had done clinical trials in the field was a revelation. After 2 months of naysaying by our local hematologist, the treatment appears to be helping.

Keep us posted.

[akita]

Dan,

"Margarete, the diagnosis that I have been given falls under the newer WPSS classifications as either RT or RCMD, which have varying prognoses. The predominant issue seems to be the refractory thrombocytopenia".

Do you mean that your thrombocytopenia is more important for your prognosis as the mild displasias in your red and white cell bone marrow?

"How would we determine if risk of progression is relatively low?"

The doctors should estimate this.

Generally the prognosis scores give a guideline to estimating, plus many extra parameters that should be assessed individually.Therefore i find that it could help trying to determine the prognosis on the basis of your FAB or WH0 classifcation, and then go further and look where your extras are. In your case this extras seem to start in the fact that, given your informations, you seem to be neither RT nor RMCD, see the WHO criteria. You could try now to check: Whats the difference between the RT resp. RMCD - Scoring and my special blood report? RT has only one dysplasia, but this dysplasia must be in the cell line where you also have the cytopenia. But you have got two dysplasias, and in the other cell lines. RMCD is only given, if you have 2 cytopenias. But you have got only one. i hope that here did not accur an error to me.. So you cannot rely on the prognoses for one of these, RT or RMCD. If you consider´beeing "in between", this could perhaps also not help much, because other parameters could lead to a poor prognosis to you in spite of the lower risk category/ies in which you seem to fall actually.= low or int-1 = "lower risk". See the article in the MDS subforum,which i posted recently and where a lot of relevant parameters for a poor prognosis are indicated. You should try to check that. Doing that with your doctor you can get more safety for prognosis I have also now copied the fulltext article in our library and would be happy to answer extra questions which have remained unclear after reading the abstract or just send you the copy by post or telefax, if you like. Further you really seem to be one of quite a lot of persons whose diagnosis lies not far away from ITP. There exist several reports concerning the differantialdiagnosis between ITP and MDs with thrombocytopenia. Maybe studying of these studies/report can bring new insights for your situation.


You could try to check these questions as a preparation for a second-opinion talk with a MDs -´specialist.

Good night!

Margarete