Science & Medicine

TSR-July 2013

(TSR) The Senyak Report

Whose MPN Awareness Day is it anyhow?
Should Jakafi patients worry about PML?


  Pacritinib, the Verstovsek Report…
  An end to bone marrow biopsy…
  Fatigue and the Benadryl effect…
  New York in Autumn, it’s spelled CR&T…
  Four grants awarded in MF Challenge

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Whose MPN Awareness Day is it anyhow?

Once again the MPN community is gearing up – more or less – to build awareness of our blood cancer by promoting an MPN Awareness Day on September 20  (Correction: MPN Awareness Day is September 12.) as part of an MPN Awareness month-long series of activities.  As MPN patients and caregivers we need to help make this effort succeed. We simply can’t afford to deputize others to do this task for us.

Last year, organizational woes and a late startbracelet light kept us from making much of an impression outside our own community… except for Incyte’s popular myelofibrosis information package of bracelets, brochures and posters.

Whatever various corporations and non-profit foundations decide to do to promote our day, MPN Awareness Day is a day for us.  It’s an opportunity for MPN patients, caregivers and healthcare providers to step up, organize some events, circulate a petition in high places and get some visibility in the halls of government and science.

We may not actually march on Washington, but we can certainly pool our combined strength to lift up our voices and petition our Representatives,  the National Institutes of Health., the Surgeon General, and the Secretary of Health and Human Services to remember those of us with this rare and often deadly disease.

You can act right now.

This coming week there are meetings scheduled to finalize a petition and supporting events and activities. Get your ideas in the mix. Volunteer to do the work. Contribute to the petition wording. Create a tagline. Design a theme.

You can do it right here.  Just drop your ideas in the COMMENT box at the end of this article.  Or e-mail your ideas to  MPNforum ( or any support organization in which you’re active: the  MPN Research Foundation, the Leukemia and Lymphoma Society, MPN Education Foundation your Facebook page or patient support group.

MPN Awareness is our cause.

Right now, with a little help from medical centers and a few non-profits, we must depend almost entirely on the investment of large pharmaceutical companies to drive drug discovery and development.

In part that’s not only because we’re small in numbers, we’re nearly invisible in the general population and barely register on the radar of major hematology conferences and meetings. Changing that will change our fortunes .  And the good news is help may be on the way.

We can expect support. The MPN Research Foundation is ready to roll out plans for an MPN Awareness program as is Incyte The MPN Coalition hasn’t been heard from officially yet but there’s reason to hope for support from that loose organization of highly skilled independent non-profits.

No matter who joins us, it’s up to each of us to lift up our voices to be heard.  If we don’t, another MPN Awareness Day will slide by, silently.  And MPN will drift back into oblivion.

If we can all get together — Patients, healthcare providers, caregivers,  the Foundations, MPN Coalition, pharmaceutical companies serving the MPN community — we might finally step out of the shadows.

The payoff?  Investment in research, shared investigative work, more patients and physicians recognizing and treating MPNs earlier, and a quicker march to understanding and possible cure.  Greater awareness of MPN means earlier treatment and better results for patients!

MPN – Together we can nip it in the blood.

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Should Jakafi patients worry about PML?

The single known case of a dreaded disease — PML — showing up in an MF patient while in Jakafi therapy, has understandably raised patient and physician concerns.

In a July 11, 2013  letter to the New England Journal of Medicine,  three healthcare providers associated with the National Health Service described the case of a 75 year old man with Intermediate Risk-2 Myelofibrosis suffering an incident of progressive multifocal leukoencephalopathy (PML) after initiation of 20 mg. twice daily ruxolitinib therapy..

“This case,” according to Dr. Dragana Milojkovic “suggests that PML may be associated with ruxolitinib treatment. After discontinuation of this medication, the worsening of the neurologic signs may have been consistent with the immune reconstitution inflammatory syndrome.(IRIS)  Although the neurologic signs developed a few weeks after the initiation of ruxolitinib therapy, it is not yet clear whether the PML was directly related to this agent.”

According to Dr. Michael Montgomery of the Incyte Medical Grouop, “It has not been determined whether development of PML in this case was related to the use of ruxolitinib. jakafi-logo An independent assessment to confirm the diagnosis and evaluate the causality assessment provided by the investigator is planned.  This is the only known case of PML in the approximately 9,800 myelofibrosis patients treated with ruxolitinib worldwide in clinical trials or with commercial product.”

Incyte has informed the U.S. Food and Drug Administration of this case and, as part of its standard procedure for sharing available information in a timely manner, is in the process of informing investigators in its clinical trials.  There are reports in the medical literature that suggest that patients with myeloproliferative neoplasms, including myelofibrosis, may be at higher risk of developing PML.

According to one MPN specialist consulted by MPNforum, “While no one should ever dismiss a case of PML or  other opportunistic infections or conditions that might emerge, one needs more post marketing surveillance to see if this is something that repeats.”

.The weblink to the Letter is:

If you’re currently taking Jakafi there is a website for full prescribing information, background and assistance: And if you or your physician still have questions about PML or IRIS, Incyte has provided a number you can call: 1-855-463-3463 

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Pacritinib — Phase III trial/Verstovsek Paper

The JAK2 inhibitors just keep coming.   This one has a Phase 3 trial underway with a new one starting later this month. Results not expected for a couple of years but the idea that a new JAK2 inhibiting molecule with new capabilities is in the pipeline has to be encouraging.  A monograph on Pacritinib by Dr. Srdan Verstovsek and associates from the leukemia department of MD Anderson was published in Drugs of the Future this month.

Verstovsek concludes “ Pacritinib (SB-1518) is a novel macrocytic compound that combines selective inhibition of JAK2 and receptor-type tyrosine-rotein kinaseFLT-3 and offers potential for the treatment of MPNs and FLT3 dependent disorders like acute myeloid leukemia.”

In January we reported on the PERSIST-1 trial from which this data is drawn.   There is now a Phase III interventional trial for Pacritinib recruiting. Information at .

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 An end to bone marrow biopsy?

Soon that fat needle pounding into your iliac crest might go the way of the doctor’s house call and the dentist’s slow speed drill. 

The object of getting you to lay down on a table and bare a bit of your butt is to extract a sample of marrow to be placed on slides, stained, and reviewed. It’s a lot of handwork both to acquire and prepare that specimen so the hematopathologist can consider the morphology of your blood cells, look at celluarlity, the shape of megakaryocytes, the landscape of your blood at a microscopic level.

It’s been possible for some time to achieve some of these objectives without the discomfort of acquiring physical samples of bone marrow and the uncertainty of handling after the specimen is acquired. PET-CT Cell imaging has moved light years beyond the technology available even a decade ago:  PET (Positron Emission Tomography) scanning  medical ultra sonography, anatomic imagery through CT (Computed tomography) imaging, MRI, infrared spectroscopy… the list goes on and on.  Now, with the advent of PET-CT scans and demonstrable improved results in  staging for Diffuse Large B Cell Lymphoma compared to the old punch and paste marrow sample method method, we might be ready to take the plunge.

Just a quick read and a glance at the PET-CET images slides in the Blood article  seems to suggest a possible improved, less painful, alternative to MPN BMB is around the corner. Any reality to this idea?

Since the work had been done at Guy’s and St. Thomas’ NHS in London, we called on our resident London MPN specialist, Dr. Claire Harrison and asked if there was a possibility of the technology coming our way.

“Yes,” she said, ” Actually we are working on it.”
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MPN Fatigue and the Benadryl effect

While Dr. Ruben Mesa’s Mayo Clinic group continues its work on a research design for our MPN Fatigue Project, here’s a report from a new front…and a new word.   The new front is histamine signaling and the word is Hypersomnia

So if you’re tired of telling people you’re tired all the time, how about saying something like,” Yeah, I have hypersomnia,  you know, idiopathic hypersomnia.”*

That way, instead of the usual clucking and sympathizing, the conversation could go something like this: 

“Idiopathic hypersomnia, wow, I didn’t know that, you sure?”

“Well, they haven’t done a differential diagnosis yet,  but you know, my MPN?  But I’m like 90% sure it’s related.”

“Idiopathic hypersomnia. Hmmm.  What causes it?  You think it’s like catching?”

“Not likely. They think  sleepiness has something to do with histamines.”

“Histamine?  How does that make sense?  Don’t histamines keep you awake?”

“Did you get that idea from your Benadryl anti-histamine hayfever meds?”

“No way, I got it from Wikipedia.  Antihistamines produce sleep.   Staying awake  is a neurotransmitter thing, firing of orexin or  hypocretin in the brain.  Somehow they’re related. The neurons producing histamines fire more rapidly when we’re awake and decline when we sleep.

“Yeah that’s the old story. The surprise discovery is the big increase in the neurons that release histamine in people with narcolepsy. And they’re speculating that could be a response to destruction of the orexin neurotransmitter in the brain.”

“So that might account for your fragmented nighttime sleep…and maybe feeling tired all the time?”

“That’s what they think might be happening.:

“They, who’s they?”

”Here, read it for yourself.  I’m going to crash.”
*Hypersomnia (Code: 780.54-7).

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finger pointing small        (Click on Graphic, Open to full size.)

New York in Autumn’s spelled CR&T

MPD Symposium Brochure 2013outside

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MF Challenge casts a wider net.

Pass the envelope please. 

This summer, the MPN Research Foundation and the Leukemia and Lymphoma Society wound up its grueling proposal review for the second round of MF Challenge grants.

After painstaking review, the leading contenders in this 2013 cycle were submitted to a panel of scientific advisors headed by the MPNRF’s Scientific Advisory Board Chair Dr. Andrew Schafer of Weil-Cornell. The winning projects are focused both on the molecular origins of MF as well as means to prevent the disease.

Here’s the rundown:

The John Varga Jonathan Licht team is looking at adipocytes – the fat cells – as a possible origin of fibrosis in MF…Golam MohiGolam Mohi is exploring the molecular mechanism in which the JAK2V617F induces MF…Emmanuelle PassegDCF 1.0is exploring how to target the remodeling of the bone marrow niche by MPN myeloid cells to prevent MF…and Xiaoli Wang is mapping the role of thrombopoietin and its receptors in MF.

As in the first round of MF Challenge grants, ” said Robert Rosen,  CEO of the MPN Research Foundation,  “each researcher will receive $100,000 over one year to test his/her hypothesis for these grants, the goal of which is to provide a proof of concept for ideas on how to stop or reverse fibrosis. Research results that show merit will be considered for additional funding, or help in acquiring additional funding, to keep the ball rolling. The most important part is the follow up. We don’t want good works to be kept in a closet somewhere.”

Rosen concluded: “There is a frustratingly low level of information about what really happens in MF, what the mechanisms of the disease really are. Our grants hope to address this hole in the MPN research world. ”

The full report is here.

© MPNforum, LLC and, 2013. MPNforum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Unauthorized use and/or duplication of this material without express and written permission is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to with appropriate and specific direction to the original content.

Comments on: "TSR-July 2013" (2)

  1. Correction: MPN Awareness Day is September 12, not September 20 which is MF Awareness Day.

  2. Obviously one can’t come to conclusions about “fat cells being a possible origin of fibrosis in MF” from this one sentence. However, it rings a bell with me, having had an MS diagnosis long ago (which may or may not have been accurate). Dr. Swank, the MS researcher, believed that white cell sclera in MS came from an autoimmune reaction to fat, particularly saturated fat. Therefore he recommended a very low fat diet, which I was on for many years (still am on a slightly modified low saturated fat diet). He discerned that Europeans had a much lowered incidence of MS dx during WWII and afterwards, when “fat” was hard to come by in the their diets. I grew up on a very low fat diet because my mom was a “dieter” for health and beauty. I did not have a major attack of MS (or was it Porphyria, or both? Doctors are unsure) until I went to college and ate the wretched fat diet at Roble Hall on the Stanford campus (gad zooks, how many triggers for Porphyria were in the dorm and the biology lab!!!). If you are confused by my post, friends, I believe some people (possibly many) have MS AND Porphyria in some relationship only postulated by some rare researchers in Oregon–and me.
    To be back to MPD and fat–the terse sentence in this article suggests “fat” cells as originators of fibrosis in MF. So….what does this mean?

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