Abstract from the ASH Conference 2010

[Birgitta-A]

Hi All,
Now the abstracts from the American Society of Hematology Conference 2010 are available: http://ash.confex.com/ash/2010/webprogram/start.html
Kind regards
Birgitta-A

[tytd]

Thanks Birgitta, You always provide us with timely, useful information. Hope you are doing well. This week's New England Journal of Medicine has results of a study of Nplate in ITP patients vs standard of care but doesn't answer any continuing questions about using it in MDS patients. Thanks Marie

[Birgitta-A]

Hi Marie,
Here is an abstract from ASH about Nplate (Romiplostim) in MDS patients:
http://ash.confex.com/ash/2010/webpr...aper33611.html

"Peripheral blasts were increased in 2 pts (MDS-U and RA at baseline) and resolved in both cases after discontinuation of romiplostim. Three cases of progression to AML were reported, corresponding to an annual on-study event rate of 5.9% (95% CI: 1.9% to 18.3%). These pts were IPSS-risk low or int-1 at baseline and had a WHO classification of RAEB-1 or RCMD. During this study, they received 750 mcg romiplostim for 6, 49, and 36 weeks. Bone marrow blasts were 39%, 65%, and 40% at AML diagnosis."

They don't report anything about increased bone marrow fibrosis that is an expected adverse reaction.
Kind regards
Birgitta-A

[akita]

Hi Birgitta,

thanks so much for posting the links to the abstracts. I looked for the abstracts cencerning chelation and saved some. When i post the links plus short comment to this forum, in which category should i post or -even better not?

Regards from a new member

Margarete

[Birgitta-A]

Hi Margarete,
Glad that you found some interesting info! There is a category called Transfusions and Iron Overload.
Kind regards
Birgitta-A
Desferal and Exjade for iron overload

[Neil Cuadra]

Here's a link to the Transfusions and Iron Overload forum.

[akita]

Thank you very much!

Margarete

[akita]

Hi Birgitta-A,

for not mentioning increased bone marrow fibrosis in the MDS-Romiplostim-Studies there might be the reason, that there have been already cases for chronic ITP with this complication, that this has caused some excited discussion and that the results of a possible investigation in relation to MDS could bring a sort of face-loss for Romiplostim in frightening the public, - but while on the other side Romiplostin could be helpful for many patients with no other options.

Adam Cuker and Charles S. Abrams commented critically at the lack of bone marrow biopsies before and after study-treatment with Romiplostin, which analyses could lead to a better understanding of the mechanisms of causing fibrotic changes by Romiplostin..

http://bloodjournal.hematologylibrar...urcetype=HWCIT

So i estimated that the near future will perhaps not bring analyses with informations. Romiplostim seems helpful in augmenting the Thrombocytes, and the MDS - patients with no other choices will be thankful for it and cope with problematic side - and longterm - effects..

As the MDs- Patients are in a special danger of converting to AML, this is an other reason to be cautious and hope for better study-informations, which do more exactly describe the group of MDS-Patients in danger to convert to AML by intake of Romiplostim. Changes by Romiplostim can seemlngly happen in a fast way, like in the old mans thrombocytopenia, where the platelets increased very, very fast in a few days, - or the lower Risk- MDs-Patients converting to AML within a short time (4 Weeks study time?)..

Regards,

Margarete

[Birgitta-A]

Hi Margarete,
You know there are two drugs that stimulate the fabrication of platelets - Nplate and Promacta. Nplate was approved a little before Promacta. They started trials with Nplate for MDS patients very early.

We still have not seen results from a single study with Promacta in MDS patients. We can hope that Promacta leads to less fibrosis and that the risk for increased blast cells is lower. What we know about Promacta is that they had to terminate a study with Promacta for hepatitis C patients with low platelets due to treatment with Interferon because the patients got too high liver tests.

At least 2 members of this forum have been treated with Promacta - I think both have developed leukemia. One member - Kirby - has continued Promacta treatment and is satisfied with the result.
Kind regards
Birgitta-A

[akita]

Hi Birgitta,

thank you for the informations. What else can positively influence the platelets? Romiplostim and Promacta have been - and are - a hope for patients with this problem. I read, that you have a sort of bone marrow fibrosis together with your MDS, i understand you being so cautious with Romiplostin.

Why could it happen in the romiplostim-mds-study that patients converted to AML in such a short time, and with so many blasts? Perhaps a closer monitoring of the peripheral blood cells if not the bone marrow would have shown the danger of transformation earlier?

Nice regards,

Margarete

[Birgitta-A]

Hi Margarete,
You know I try to avoid everything that can possibly decrease platelets or increase bleeding risk. Many drugs for example pain killers decrease platelets and a lot of food can prevent blood clotting. For example green tea, onions, garlic, blueberries, dark chocolate etc are good for persons with normal platelets - they prevent blood clotting and arteriosclerosis. I dare never eat this kind of food.

There are many drugs that can increase platelets in a some patients - all drugs for MDS patients like Vidaza, Dacogen, Revlimid and so on can improve counts. Four weeks after I started to take Thalidomide my platelets increased to 43 from 22 and now after 6 months they are between 70 and 80.

As far as I have understood they looked for both increased fibrosis and blast cells during the trials with Nplate and in several cases the blast cells decreased when Nplate was stopped.
Kind regards
Birgitta-A

[akita]

Originally Posted by Birgitta-A

Four weeks after I started to take Thalidomide my platelets increased to 43 from 22 and now after 6 months they are between 70 and 80.

That sounds wonderful. How long do you think will Thalidomide work? Are there any studies?

Originally Posted by Birgitta-A

As far as I have understood they looked for both increased fibrosis and blast cells during the trials with Nplate and in several cases the blast cells decreased when Nplate was stopped.

Is it really proved that they looked also for increased fibrosis during the trials with Nplate/MDS? As there is nothing mentioned in the study reports we cannot be sure..

As i remember this decreasing of blasts happenend after cessation of Nplate only after a short intake-period and nobody knows if this reversible-effect would also work after blast encreasing after a longer period of NPlate.

I wonder how it could happen that there was a such rapid, high blast encreasing with the two MDS patients who transformed into AML without (any?) notice of the study-management. Could these transformations have been prevented during the period the blasts were increasing?

Also it seems quite strange that blasts in MDs go back after the cessation of a medication. Did you hear from such a fact earlier?

Regards,

Margarete

[Birgitta-A]

Hi Margarete,
There are at least 10 studies about Thalidomide in patients with Myelofibrosis and I have found 3 in patients with MDS. The range of the response is wide - 1 to 37 months. Then I read an abstract from ASH 2010 where 8 patients with MF had got Thalidomide or Revlimid with Interferon alfa injections and 2 patients responded more than 5 years.

Since FDA specially has warnings about Nplate in MDS patients due to risk for increased fibrosis and blast cells I think they have to try to show that the drug doesn’t harm these patients - they can get both increased fibrosis and blast cells due to their disease.

In this abstract from ASH 2010 they report about treatment from 6 to 134 weeks:
http://ash.confex.com/ash/2010/webpr...aper33611.html

We have to wait for the article in some journal if we want to know details for example if they did look for increased fibrosis.
Kind regards
Birgitta-A

[mcgill54]

The latest data on nplate seems a bit more positive than the earlier reports. My platelets have gone down to 26K after being stable for 4months at 36/37.They recommend Nplate when they reach 20K, and my Dr has 3 patients who are taking it now. It seems as if there are no good choices for this condition and waiting for clearer data re fibrosis, blasts etc will take too long for me. So..what to do??? best regards to all, hope the new year brings good things to us and the world

[akita]

> It seems as if there are no good choices for this condition and waiting for clearer data re fibrosis, blasts etc will take too long for me. So..what to do???

There has been a posting in this forum where a member reports that he takes only a small quantity of Romiplostin, less than adviced normally, which leads to stabilizing the platelet count between 20 and 30. Sorry, - i could not find this posting! I hope that i reported it correctly!

Such a solution, if it works in a patient, could supposedly help minimizing the potential negative side-effects, - on the other hand you will perhaps not experience high platelets..

Kind regards,

Margarete

[Birgitta-A]

Hi Mcgill,
Yes, the first report was quite alarming with several patients that got increased blast cells after 28 days. Then FDA warned about Nplate for MDS patients. Now I have seen reports where less patients develope AML after long term use of Nplate than MDS patients without Nplate.

Hi Maragarete,
Yes, a low dose of Nplate would probably be OK. Even for patients with Immune Thrombocytopenic Purpura (a bleeding disease) Amgen advices low doses - they should not try to get normal platelet counts.
Kind regards
Birgitta-A

[akita]

Hi Birgitta,

> Now I have seen reports where less patients develope AML after long term use of Nplate than MDS patients without Nplate.

Where can i find these reports? (If its not too long work for you to search).

Kind Regards,

Margarete

[Birgitta-A]

Hi Margarete,
Unfortunately I can't find the report about progression to AML in patients with or without Nplate treatment. I have looked at many abstracts without finding it so it must have been in a review article. If I see that info again I will post it.
Kind regards
Birgitta-A

[akita]

Hi Birgitta,

thank you very much for your searching for the paper you mentioned.

When i try to find something again which i met only a few hours or days ago, i almost always cannot find it. It seems as if this shamanistic pathways are very situation-bound and cannot be repeated exactly.

When i have much time i would like to make a list of all the papers about Romiplostim. It is otherwise not possible for me to get an overview. You seem to be already very experienced with this topic, this makes it probably easier to follow the actual discussions and to see the relevant details, interesting for patients..

Today is Christmas Eve. My children have been there for a visit. My two appartment - mates have gone out. Now it is a peaceful evening for me.

Hope you are having a good time also.

Kind regards,

Margarete

[akita]

Originally Posted by Birgitta-A

Yes, a low dose of Nplate would probably be OK. Even for patients with Immune Thrombocytopenic Purpura (a bleeding disease) Amgen advices low doses - they should not try to get normal platelet counts.
Kind regards
Birgitta-A

Hi Birgitta, look, there is a study from the this year ASH. MDS Patients with platelet-counts 0-20 and 30-50 had a lower survival than the patients with 20-30.

2905 Associations Between Platelet Count and Survival and Disease Progression In Thrombocytopenic Patients with Myelodysplastic Syndromes

http://ash.confex.com/ash/2010/webpr...aper27261.html

Perhaps therefore it is not so extremely necessary to try to come to a higher level than 30 by intaking the normal dosis of Romiplostim. If a small dosis leads to 20-30 this could probably be sufficient as compromise: lower platelets-lower intake of Romiplostim- lower rate of side effects/adverse events?

Platelet counts in the range of 20-30 seem quite low compared to "normal" ones.

Do you know if it is possible to assess in advance the individual risk for dangerous bleedings in this range?

(i remember having read something in the direction that the functioning of the platelets can differ considerately..)


Kind regards,

Margarete

[Birgitta-A]

Hi Margarete,
You know it is not only the platelet count that is important but the platelet function too. In MDS the platelets can be dysfunctional (mine are dysfunctional) so to assess the bleeding risk there is a test called PFA 100 (Platelet Function Analyzer).
http://www.medcorp.com.br/medcorp/up...9105163930.pdf

As you understand it is difficult to know when there is a risk for bleeding if you only measure the platelet count but most clinics don't give platelet transfusions if the patient has a platelet count of 20 or more. If the patients has severe bleedings from nose, mouth, rectum and so on they often give platelet transfusions even if the platelets count is higher.
Kind regards
Birgitta-A

[akita]

Originally Posted by Birgitta-A

Hi Margarete,
You know it is not only the platelet count that is important but the platelet function too. In MDS the platelets can be dysfunctional (mine are dysfunctional) so to assess the bleeding risk there is a test called PFA 100 (Platelet Function Analyzer).
http://www.medcorp.com.br/medcorp/up...9105163930.pdf

As you understand it is difficult to know when there is a risk for bleeding if you only measure the platelet count but most clinics don't give platelet transfusions if the patient has a platelet count of 20 or more. If the patients has severe bleedings from nose, mouth, rectum and so on they often give platelet transfusions even if the platelets count is higher.
Kind regards
Birgitta-A

Thank you, dear Birgitta,for the informations, which gave me the opportunity of ongoing study this sunday.

As i understood from the Platelet Function Analyser, there is a difference in the platelet function whether the patient has "Destructive" or "Underproduction" Thrombocytopenia. For MDS patients this could mean,that thrombocytopenia with immune problems has on the other side advantages in regard to platelet functioning. I think i could also read today that these patients usually do not have dysplastic thrombocytes. "Underproduction" Thrombocytopenia in MDS has often platelet dysplasias and their platelet functioning is often decreased.

There exists a (one or more?) platelet consensus report from 1998. The conference leading to this report did not consider the läter happening expansion in the development of platelet function awareness. In a new consensus conference this will surely to be included in the discussions.

Also i could read today in a study that 20 % of the MDS-Patients with Thrombocytopenia died when this problem was combined with others, and 10 % solely because of the Thrombocytopenia. It should not be common to think that these deads happen because of the natural course of the disease, but instead it should be investigated in the very special case, why this dead occured and how this could have been prevented. In some cases the person probably did not reach the transplantation unit in time, or even he/she was not given the transplantation because of too high platelet values (but with bad functioning)...

Maybe it could help in some cases to have a sort of diary, where the patients writes down all the special problems with thrombocytopenia, bleedings, the blood counts, a list of current medicaments and treating docters.. And then show this in case of difficulties with the transfusions...

..
Kind regards


Margarete

[akita]

Pubmed.org

Consensus conference on platelet transfusion: final statement.
[No authors listed]
Br J Cancer. 1998 Aug;78(3):290-1. Review. No abstract available.
PMID: 9703272 [PubMed - indexed for MEDLINE] Free PMC Article Free
text
http://www.ncbi.nlm.nih.gov/pmc/arti...9/?tool=pubmed

There are another - at least - 7 Papers to this conference/discussion on www.pubmed.org with search words Conference platelet transfusion

Regards,

Margarete

[akita]

http://www.ncbi.nlm.nih.gov/pubmed/21152677H
with free fulltext

Hamostaseologie. 2010 Dec 9;31(2). [Epub ahead of print]
Platelet function testing in clinical diagnostics.

Rechner AR.

Dr. Andreas Rechner, Siemens Healthcare Diagnostics Products GmbH, Assay Development Haemostasis, Emil-von-Behring-Str. 76, 35041 Marburg, Germany, Tel. +49/(0)64 21/39 31 81; Fax +49/(0)64 21/39 46 80, E-mail: andreas.rechner@siemens.com.

"This article intends to provide an overview of the current platelet function tests such as light transmittance aggregometry, whole blood impedance aggregometry, the PFA-1001 system, the VerifyNow2 system, flow cytometry, as well as other promising technologies like Plateletworks3, IMPACT-R4, PADA, thromboelastography, and the mean platelet component (MPC), briefly addressing strengths, weaknesses and clinical utility of these tests."

[Birgitta-A]

Hi Margarete,
You know many patients with low platelets don't get better after platelet transfusions because the new platelets are destructed at once. Even if they try HLA matched platelets the platelet count can be very low.

In Sweden PFA 100 is used at most clinics but I don't know my value because when I got my dx they only used bleeding time that was supposed to be valueless but they didn't have any better methods. My bleeding time was more than 21 minutes - they didn't measure more than that.

Very interesting info you posted!
Kind regards
Birgitta-A
71 yo, dx MDS Interm-1 May 2006, Thalidomide since June 2010, platelets increased from 22 to 81 (latest count)