Seeking Veterans with MPN

Dear Vietnam Veterans and Family Members,

In an effort to collect valuable information that will help our cause with the VA and the independent study that will be conducted by Dr. Raajit Rampal at Memorial Sloan Kettering, MPN Advocacy & Education International has devised a list of questions that will serve as an essential data source moving forward.

 Please take a few moments to review the questions and if you are able, please add your information. Note: Leaving your contact information is optional, not required.

Thank you for your time and willingness to help further the exploration into the dangers of Agent Orange exposure and MPNs.

Click here to begin questionnaire


Ann Brazeau, CEO

MPN Advocacy & Education International

The Ultimate Blood Brothers


Ron Anderson

Ron Anderson, LA Support Group Coordinator, received a bone marrow transplant eight years ago.  His brother, a perfect match, was his donor.  We asked his brother to share his experience to get a donor’s perspective.

Was there ever a time, once you knew you were a perfect match for your brother, that you thought you would not be his donor?

No, by the time his doctor told him he needed a bone marrow transplant he was seriously ill and probably would not survive for very long without a total transplant.  As it turned out, my brother and I have type A+ blood and (thank God) I turned out to be a very good match for him.  I just felt very fortunate I would be a great donor and could help him.

When I told him I was willing to be his donor I thought I would be going into a hospital operating room and have doctors use needles to remove my marrow from my pelvic bone.  Later, I found out about Peripheral Blood Stem Cells (PBSCs) and a process called apheresis.  My stem cells could be collected by drawing blood out of my veins, filtering them out and the rest of my blood would be given back to me.   I was very pleased to learn about this nonsurgical method.

How has this experience changed you?

For the first time I took a hard look at my entire family’s age/health issues and felt there was a real possibility that I might not have any family members alive in the next 5 to 10 years.  That was not a very comforting thought for me.  I think this experience with Ron not only strengthened my relationship with him but with my entire family.  Since Ron’s transplant in 2009 I have tried not to take my family for granted.  Since 2009 both of my parents have passed away but I am very thankful I still have my two brothers.

What, if any, were the side effects?

The only side effects I can remember was some mild hip and shoulder joint pain issues after taking the drug Neupogen to increase my stem cell production.  It went away within a reasonable time frame (I think about a couple of weeks) after I stopped taking that medication.  The only other issue I experienced was during my hospital blood collection time when I had some tingling around my mouth apparently from decreased calcium blood levels from the filtering process of my stem cells.   That tingling totally stopped after the apheresis when completed.

Can you briefly explain the experience in the hospital?

All the hospital staff were great and they gave a very good explanation of what would be happening during my stay.  They were very caring and made me feel very comfortable during the apheresis process.

In the hospital, I sat in a comfortable lounge chair for about 6 hours a day for 2 days (because I also agreed to give extra cells to stem cell researchers) squeezing a soft ball with my hand during the stem cell collection process.  As my blood calcium levels dropped during the apheresis procedure calcium had to be replaced back into my vein which sometimes caused that vein to fail and infiltrate.  I think the worst part of the hospital stay was the restarting of new I.Vs.  I had about 4 or 5 new I.V. restarts a day and some pretty good bruises on the back of my hands and forearms by the time the apheresis was completed.  At the end of the day, a very small price to pay for helping my brother.


What’s New in the MPN Mutation World

By Marina Sampanes Peed

The identifiers among people living with Myeloproliferative Neoplasms (MPN) are getting more complicated, thanks to all the discoveries in the last few years. We tend to identify ourselves with the current diagnosis and gene mutation(s) identified through bone marrow biopsy or blood tests.

Here’s a typical conversation at a conference for MPN patients:

“Hello! My name is ______ and I have PV. JAK2 positive. What about you?”

“Hi. I’m ____ and I have ET. I’ve got the CALR. What are you taking – Hydrea or Pegasys? Any Jakafi?”

With a more thorough understanding of the disease pathogenesis comes refinement in treatment options. Researchers and clinicians around the world are working on both aspects. Gene mutations occur in three ways: insertion of code, deletion of code, or substitution of code.

JAK2V617, CALR and MPL account for 95% of all MPN cases.  Several epigenetic mutations are now known to impact MPN.  Mutations change over time.

Initiating Mutations: JAK2 leads the way

The first gene mutation associated with MPN was discovered in 2005. It’s called JAK2V617. The following year, the MPL (referred to as “mipple”) mutation was identified and in 2013, mutation of the Calreticulin (CALR) driver gene was identified in some ET and PMF patients.

All three affect signaling/regulation in the cells. The mutations signal the cells to stay “on” constantly.

mpn mutationThe JAK2 and CALR mutations give the clonal stem cells a selective advantage to produce more than healthy stem cells. The mutant stem cells go on to produce more myeloid cells (red blood cells and platelets). This promotes a self-reinforcing malignant niche that also triggers cytokine inflammatory reactions. The inflammation process contributes to the constitutional symptoms MPN patients experience.

Calreticulin (CALR) is a driver gene. The mutant CALR induces disease and it also creates excessive megakaryocytes. It also activates the MPL and the JAK2 -> STAT signaling pathway.

The mutation on the CALR gene occurs at the end of the coding sequence (the telomerase).

CALR mutation occurs only in Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). It was discovered with Genome Wide Association Studies.

JAK2 signals cells to do their jobs. It signals several pathways: STAT, MEK, P13

There is second mutation on the JAK2 gene, called JAK2 exon 12. It is different from JAK2V617F+ and is prevalent in less than 5% of patients. Patients may have one, but not both JAK2 mutations.

Interestingly, some people with the JAK2 mutation do not develop a MPN. This fact leads researchers to believe that there are more mutations at work with MPN activity.

MPL is a Thrombopoietin receptor and shows up in patients with ET and PMF.

Epigenetic Mutations

Each mutation affects the microenvironment of the cells (stimulating cytokines and triggering inflammation). Those changes then foster new mutations. Several are considered co-operating mutations needed for disease initiation and progression: TET2, CBL, IDH, IKZF1, EZHZ, DNMT3A, EZH2, SETBPI, ASXL 1 exon 12.


Q:    Should MPN patients test for mutations regularly?

The various cooperating mutations are still being identified. We’re not sure what the numerous combinations mean in terms of disease progression, symptom burden, etc. In general, the information is still not actionable. While it may be interesting, insurance companies are not likely to pay for tests that will not necessarily affect treatment decisions.

Stanford has a 54 gene myeloid mutation panel used in transplant decisions for myelofibrosis only.

Q:    Can we use the CRISPR to cut and replace the aberrant gene?

This is being studied with sickle cell patients. But that disease process functions differently from MPN. With MPNs, every mutated stem cell would need to be fixed (which is not needed for sickle cell). There are also many unknowns for off-cutting effects.

Q:    Will immune therapy, such as CAR-T therapy, be a cure for MPN?

CAR-T therapy is in the news for treatment of lymphoid leukemia. It is easier to live with fewer lymphocytes. It is much more difficult to get rid of bad myeloid cells without interrupting critical processes for red cell and platelet production.

In addition, there is much less uniformity in myeloid cells, so it would be difficult to develop effective CAR-T for each patient.

Q:    How important is the Allele Burden of my mutation?

The Allele is not an indicator of the severity of disease. Some MPN patients have low allele and significant disease; others have high allele and indolent disease. It is information that is considered with all the other signs and symptoms in the clinical setting.

Q:    If the driver mutation (JAK2V617, CALR, MPL) is gone, will the MPN go away?

Not necessarily. While these genes trigger the clonal production and high blood counts, there are other changes, like the epigenetic regulator mutations, which are meaningful. Even after an allogeneic transplant, a disease may recur due to the support system for clonal cells creating a leukemogenic environment (hospitable to aberrant cell behavior).

Vietnam Veterans Update: MPNs on VA’s Agenda Finally

Ann Brazeau, CEO, MPN Advocacy and Education International, and Dr. Raajit Rampal, MD, PhD, Memorial Sloan Kettering Cancer Center, attended an “open” meeting held by the US Department of Veterans Affairs with the National Academy of Sciences’ (NAS) Committee on Agent Orange and Health. The meeting, held in Washington, DC on March 1st, addressed myeloproliferative neoplasms for the first time ever. They are now being considered for further studies. Both Ann Brazeau and Dr. Rampal presented arguments to the committee regarding compensation and benefits to all veterans with an MPN, and related the scientific examination required to finally test the link between Agent Orange/Dioxin and myelofproliferative neoplasms.

A new committee has been established by the National Academy of Sciences (NAS) that will conduct a review and an update of scientific evidence regarding statistical associations between diseases and exposure to Dioxin and other chemical compounds used in Vietnam.

Dr. Rampal will begin his study in the near future. MPN Advocacy & Education International will be sending a questionnaire to all veterans affected by MPNs to begin collecting needed data to defend our case. In the meantime, we are completing a package that will help assist veterans with their claims.


Susan Hill: Idaho Support Group Coordinator


Susan Hill

My journey with myelofibrosis (MF) began in 2001 when I was diagnosed just as I was celebrating my 60th birthday. The diagnostic process took several months of lab tests, xrays, biopsies, etc. When the hematologist told me that I had MF, he said only that there was no cure and he would treat the symptoms. Later he added that MF was a “ten year disease.” There was no patient education information, no suggestion of a second opinion, no explanations of the aspects and course of the disease. My knowledge of MF was only what I could find online. MF was one of the MPDs, myeloproliferative disorders, not yet classified as a cancer.

As my MF progressed, my worst symptoms were fatigue and an ever-enlarging & painful spleen. With no treatment for those symptoms, I was told they were “part of the disease” and dismissed as such. I avoided transfusions by taking large doses of injected Aranesp (epoetin alpha) for several years. But as my fatigue and spleen issues became unbearable, I was losing weight and could barely function. By 2009 it became clear that I was not going to survive much longer.

Thankfully, after “firing” one hematologist, I became a patient of our local cancer center’s medical director. He immediately sought a clinical trial for me and was successful. I was accepted for the Comfort – I study, a phase three trial of Ruxolitinib. In April, 2010, I began taking the study drug. Within two weeks my spleen was shrinking, my fatigue was improved, and I deduced that I had gotten the “real” drug rather than the placebo. In four weeks my spleen had shrunk more than 25% and my prognosis was vastly improved.

Now, after seven years on Ruxolitinib, now known as Jakafi, my MF is stable, my spleen is almost normal size, and my fatigue is manageable. Needless to say, I am a big “fan” of clinical trials.

In 2011, I started a support group for MPN patients here in Idaho and began working with patients across the country online and by telephone. The prime “lessons” we teach and learn in our group is that we each must become our own advocate with our doctors and the community and we need to learn as much as possible about MPNs.

It feels so supportive to be part of a “family” of MPN patients, knowing that we all help each other. Today’s MPN patients are fortunate to have a community focused on our diseases, to help us through patient education and advocacy.

Stemline Therapeutics Provides Update on Clinical Programs

NEW YORK, Feb. 21, 2017 (GLOBE NEWSWIRE) — Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel therapeutics for oncology indications of unmet medical need, today provided an update on its clinical programs.


  • Patient enrollment has continued to advance, without interruption, in all SL-401 clinical trials across multiple indications, including the Phase 2 pivotal trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN).
  • Given the enrollment trends, the projected timeline for completing enrollment in the final cohort (Stage 3) of the BPDCN pivotal trial remains on track for this quarter.


  • Patients with advanced solid tumors are currently enrolling into a Phase 1 dose escalation study involving six centers. Four dosing cohorts have been completed, and enrollment in the fifth cohort is ongoing. Further trial updates are expected later this year.


  • In a Phase 2 trial, adult patients with second-line glioblastoma received SL-701 alone or in combination with bevacizumab. The trial has been completed, and patients are being followed to assess survival. Further updates are expected later this year.

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Today is Rare Disease Day 2017!

Today is #RareDiseaseDay 2017! Today, with events taking place in over 90 countries all around the world, we hope to raise more awareness than ever for rare diseases!

With the theme of research, and the slogan, ‘With research, the possibilities are limitless’, #RareDiseaseDay 2017 is an opportunity to call on all researchers, universities, students, companies, policymakers and clinicians to do more research and to make them aware of the importance of research for the rare disease community.

This year’s Rare Disease Day video, which has been viewed over a hundred thousand times and translated into over 30 languages,  draws a parallel with a routine that many of us go through multiple times a day – searching for an answer on the internet. The video highlights how isolating it is when you search on the internet but receive the response ‘your search had no results’. It also highlights the hope and promise that comes with additional research into rare diseases, something that must be continuously strived for. 

You are still able to participate in raising awareness of the day and be part of the change, by sharing the video, the poster, or any Rare Disease Day material on your Facebook, Twitter or other social media platforms.

This year, on the tenth edition of the day, Rare Disease Day events will be held for the first time in four African nations, Botswana, Nigeria, Senegal and Sudan. Events will also be held for the first time in Saint Pierre and Miquelon.

Initial Trial Results Show Novel Agent Slows High-Risk MF

A third of patients with previously treated, high- and intermediate-risk myelofibrosis had objective responses to the investigational second mitochondria-derived activator of caspases (SMAC) mimetic LCL161, results of a small phase II trial showed.

Seven of 21 evaluable patients had improvement in 1 or more clinical parameters during treatment with LCL161. The treatment was generally well tolerated with weekly oral dosing. Grade 3/4 toxicity consisted primarily of anemia and thrombocytopenia, as reported at the American Society of Hematology meeting in San Diego.

“LCL161 has a convenient dosing schedule, has a novel target for patients with myeloproliferative neoplasms, and is able to be administered to patients who have failed or demonstrated intolerance or are otherwise ineligible for JAK inhibitor therapy,” said Naveen Pemmaraju, MD, assistant professor of leukemia at the University of Texas MD Anderson Cancer Center in Houston. “Grade 2 fatigue was the most common toxicity observed, resulting in 6 out of 7 dose reductions during the study. This study has met criteria for preplanned analysis for safety, and therefore is now enrolling in stage II.”

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