International MPN News, Science & Opinion

Ruben’s Raiders

Research into the whole MPN patient

Frustrated with the business of MPN medicine, the  string of failed clinical trials and costly meds?  There is an MPN oasis in the sun. The Mayo Clinic campus at Scottsdale, Arizona is headquarters of the MPN master physician, Dr. Ruben Mesa and his brilliant, passionate team. Together they have revolutionized MPN diagnostics and are now setting their sights clearly on MPN alternative therapy.

Primarily known for his compassionate, skilled MPN patient care and award winning MPN educational videos, there’s another side to Mesa, the scientist and researcher. He is the primary driver for MPN patient-involved quality of life research.

A14 RubenTheirs is not research supported by drug money or even NIH grants. This is science probing the hard to define feelings and self-recognized states of MPN patients translated into quantifiable data that can be used to create solutions while validating clinical assessments.

At the heart of this research is direct patient participation. One of the first achievements is the universally used MPN Symptom Assessment Form, the MPN-SAF.

A tailspin to discovery

I had a chance to see for myself how the MPN-SAF worked. I had already assembled the elements to this story, when a traumatic event occurred. Unexpectedly, the masked symptoms of pancreatic cancer brutally unmasked and my dog Jenny died.  On my desk were abstracts and PDFs of dozens of Mayo Scottsdale MPN scientific papers. My computer screen littered with pages and links to still more papers, notes of interviews and a full outline of this article.

But all my efforts to have at it and soldier on through were useless. My mind was spinning, Simple tasks went unfinished, my concentration was gone, even my walk was wobbly. For two weeks, when not sleeping or suddenly finding myself waking up or staggering to bed, I was dizzy and depressed, without appetite.

Problem is these are all elements of myelofibrosis. They are also components of aging and companions to grieving and depression. Since I was at the time an old, grieving, depressed MF patient, I had an opportunity to assess the MF version of the  MPN-SAF from the inside out, instead of checking off notes as a reporter.

Could this instrument tease out the real life circumstances in which my myelofibrosis was embedded and provide an accurate assessment of my MPN status?

It could and it did.  The simple expedient of checking off boxes relating to how much difficulty I had with each symptom in the past week enabled to me to clearly see the shape of my MF landscape apart from acute grief.  And that realization helped get me back on course. The enormous achievements of the Mayo Clinic-Scottsdale team need to be known and celebrated by our MPN community.

Although the main thrust of this work so far is diagnostic and not prescriptive, when attached to alternative and integrative medical procedures – which is happening now (see below) – this patient-centered research offers immediate hope for relief and long-term clinical improvement. And it offers this hope without side effects or need for insurance company approvals.

Ruben’s Raiders change the MPN landscape

Dr. Holly Geyer (r.) discusses patient with Dr Jeanne Palmer

Dr. Holly Geyer (r.) discusses patient with Dr Jeanne Palmer

With announcement this week of a new MPN project, the SIMMs Study and publication of the results of Dr. Holly Geyer’s paper on gender and MPN symptoms, the Mayo Clinic-Scottsdale group expands its historic role in defining whole patient-centered scientific research.

While key players have been Drs. Ruben Mesa, Holly Geyer, Robyn Scherber and Amylou Dueck, PhD, statistician, with back up from dozens of colleagues,  there are hundreds of people invovled in the Mayo Clinic-Scottsdale driven effort through the MPN Quality of Life consortium.

At JCO chart with Amy Dueck

At JCO chart with Amylou Dueck

Dr. Robyn Scherber

Dr. Robyn Scherber

MPN-QOL is a large group of dedicated international MPN investigators. One of the first tasks of the MPN-QOL was to validate the MPN-SAF Diary for tracking symptomatic response in patients on therapy.

Assessment and improvement of MPN Quality of Life is the chief focus of Ruben’s Raiders.  The aggressive research and publishing effort coming out of Arizona may well hold the key to our short-term QOL improvement. Here’s why.

How we went off the rails

The Mayo Scottdale approach seems so logical:  Enlist patients to report their symptoms in an effort to stratify MPN disease and seek alternative remedies. So why is more than 99% of the MPN medical research budget spent on strictly physical, drug-related projects and trials? A pioneering exception: Mesa with the late Joyce Niblack enlisted on-line patient participation in the landmark fatigue study published in 2007. But in general MPN patients are the object of scientific study and not participating partners in discovery. And there is plenty to be discovered.

Partly, of course, it’s all about money. There’s money to be made in drugs that relieve symptoms. Not so much in complementary alternative therapies. But even more significant is the impact the  sheer novelty of new biological knowledge and technology has had on researchers and institutions.

...with Joyce Niblac

…with Joyce Niblack

There are 37.2 trillion cells in our body, more or less.  Until recently they were all mysterious. It’s only been in the last 150 years that we had any idea that these cells were the biological unit of life for plant and animals alike. And not more than 75 years since we discovered the DNA double helix at the heart of the cell nucleus that coded for the 20,000 or so proteins that build and drive our biologic processes. Finally, the human genome was only sequenced 15 or 16 years ago

So it’s understandable that drug companies and medical researchers  would jump on all the new equipment and techniques devoted to studying the molecular biology of this expanding new world. And end up focused on  the mutational basis of myeloproliferative neoplasms.

It took the work of Dr. Ruben Mesa’s group at the Mayo Clinic-Scottsdale to help redirect the scientific study of MPNs to its true subject: the living whole MPN patient in his or her psycho-social, messy, complex living reality of perceptions, hopes, fears, responses, and feelings.

Unintended benefits. Along the way, thanks to all the publications, posters, and presentations we got to lift up our view from our own proliferative belly buttons and see our fellow MPN patients worldwide. We knew about fatigue but this research showed us that we were not alone suffering with headache, sexual dysfunction, depression, insomnia and all the other familiar clinical symptoms.   MPNs  stepped out of the darkness and emerged as a disease affecting the whole person and not just a matter of JAK-STAT pathways and cytokine storms.

The MPN-SAF

The beginning was announced in 2006 with publication in Cancer of The burden of fatigue and quality of life in myeloproliferative disorders.  In its direct approach to MPN patients this was an historic publication in many ways. The survey leveraged the internet to assess the fatigue burden of 1179 MPN patients and the impact on their quality of life of multiple MPN symptoms. The Brief Fatigue Inventory was used along with other generic statistical tools.  What didn’t exist was something that could quickly and accurately assess an MPN patient’s risk status and condition along replicable, universally recognized lines. What did not yet exist was the MPN Symptom Assessment Form.

In Holly Geyer’s words from the Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development

The Myelofibrosis Symptom Assessment Form (MF-SAF) was created in 2009 and served as the first validated MPN Patient Reported Outcome (PRO) tool to be made available for clinical and trial settings. A 20-item instrument, the survey attempted to capture the most common symptoms within myelofibrosis and content included issues related to catabolic/proliferative symptoms, quality of life, fatigue, and splenomegaly-associated issues. Questions were constructed in a “yes,” “no,” or 0 (absent) to 10 (worst imaginable) scale. The tool proved useful in the open label phase II trial of the JAK2 inhibitor, ruxolitinib.

This tool was followed two years later by the widely used MPN-SAF extending the technology to PV and ET and expanding the scope of symptoms surveyed. The MPN-SAF has been used successfully in evaluating effectiveness of various compounds including ruxolitinib and interferon.

MPNSAF 1

MPNSAF 2

And now, the next step, the SIMMs study.” Survey of Integrative Medicine in Myeloproliferative Neoplasms.”

At a high level we are trying to flesh out opportunities of non=pharmacologic therapies for MPNs to combat fatigue and other difficulties.”

   -Dr. Ruben Mesa on the SIMMS Study

The call to participate in the SIMM Study … This is our time to step up a bit, as we have in the past.

The SIMMs survey is long, probably taking 15 minutes to complete. We’ve been over some of this territory before as well in earlier studies. But it’s vital to persevere since Dr. Krisstina Gowin is developing direct associations between demographics and phenotypic data and surveying MPN patient alternative and complementary  therapies.  The SIMMs study is the next crucial step in designing a clinical trial of alternative and complementary therapies.

Dr. Krisstina Gowin, a Research Collaborator at Mayo Clinic Scottdale, recently left Arizona to join her husband in the Salish Integrative Oncology Care Center in Washington State.  Gowin maintains her research affiliation with Ruben’s Raiders and has taken the lead in the the SIMM study: Survey of Integrative Medicine in Myeloproliferative Neoplasms. This has long been the holy grail in searching for non-pharmacologic approaches to MPN therapy that can support standard medical practice.

The SIMM Study
Survey of Integrative Medicine in Myeloprolifertive Neoplasms
Drs. Ruben Mesa and Krisstina Gowin, Mayo Clinic AZ
To complete and submit click on this link:
https://src.co1.qualtrics.com/SE/?SID=SV_cYKR9O18hhVKMqF

Physician and patients  have long recognized that many MPN symptoms, notably fatigue, have a psychological component and a multi-disciplinary approach to treatment is mandated. Patients have been demanding it for years.

What we need as patients, and what our physicians and clinics might consider providing as a clinically and fiscally effective measure, is a routine strategic collaboration among traditional medical, psychological  and alternative, complementary therapies.  MPN is a whole life experience, affecting our plans, relationships, work, thoughts, feelings and self image as well as our spleens.  It is part of our being, not simply a breakdown of machinery that needs to be repaired.  Treatment of MPN requires a whole team approach….including specialists on our team to address the severe impacts of MPN on our cognitive, emotional and economic being.

Fatigue Project statement of purpose, April, 2013:

Dr. Kristina Gowin

Dr. Krisstina Gowin

The work of Dr. Krisstina Gowin within the Mayo Clinic Scottsdale matrix advances that objective. Her SIMs study — launched with Ruben Mesa and Dr. Denise Millstine, direct0r of Integrative Medicine at Mayo Scottsdale — is the next necessary step toward clinical trial.  Athough the lengthy questionnaire does not probe the effectiveness of the various alternative therapies employed by MPN patients, its association of disease states and demographics leads directly to such a research design.

In fact, one such design is already circulating at Mayo Clinic Scottsdale.

Social and psychological intervention in an MPN clinical trial.

A young colleague on the Scottsdale campus, Dr. Leslie Padrnos, developed a pilot study Patient Empowerment in Myeloproliferative Neoplasms through Acceptance and Commitment Therapy (the PEMNACT Trial).  This is one of the ways all this comes together.

The payoff for the Fatigue Project and the study of MPN demographics, phenotype association studies, symptom analysis and assessement of patient alternative strategies in current use is clinical trial of alternative therapies. Padrnos has proposed initiating an MPN trial based focused on empowering patients through techniques based on Acceptance and Commitment Therapy (ACT) and the work of social psychologist Dr. Steven Hayes. This is a psychological intervention focusing on thought content and identification of beneficial activities

“With a high level of symptoms and scarce therapeutics, “ says Padrnos, “MPN patients experience lifelong burden. The unmet needs of MPN patients exceed the need for development of pharmacotherapy alone. This patient population needs interventions aimed at addressing symptom burden or empowering patients with improved coping strategies, supportive care or education on symptom management.”  Spoken like a true researcher in Ruben’s Raiders.

line short red red 50%

The birth of a new MPN paradigm

Selected links
MPN-SAF: http://www.bloodjournal.org/content/bloodjournal/118/2/401.full.pdf?sso-checked=true
MPN-10: http://jco.ascopubs.org/content/early/2012/10/15/JCO.2012.42.3863.full.pdf
Fatigue project: http://onlinelibrary.wiley.com/doi/10.1002/cncr.29753/abstract
Medical comorbidities abstract: http://www.bloodjournal.org/content/124/21/1862
The MPNforum 2013 Fatigue Project ASH report with posters and video.
Disease duration and symptoms: https://ash.confex.com/ash/2015/webprogramscheduler/Paper80959.html
Psychological comorbidities: http://www.bloodjournal.org/content/124/21/3173?sso-checked=true

 

Selected documents

The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients.  Mesa RA(1), Niblack J, Wadleigh M, Verstovsek S, Camoriano J, Barnes S, Tan AD, Atherton PJ, Sloan JA, Tefferi A.] Cancer. 2007 Jan 1;109(1):68-76.

Sexuality Challenges, Intimacy, and MPN Symptom Burden: An Analysis By The MPN Quality Of Life International Study Group (MPN-QOL ISG)  Blood 2013 122:4088;

Gender differences and MPN symptom burden: An analysis by theMPN quality of life international study group (MPN-QOL ISG) H Geyer, R Emanuel, A Dueck, JJ Kiladjian… – Haematologica ( …, 2014 – diva-portal.org
bloodjournal.org
Sexuality challenges, intimacy, and MPN symptom burden: an analysis by the MPN quality of life international study group (MPN-QOL ISG) AC Dueck, RM Emanuel, K Cannon, JJ Kiladjian… – Blood, 2013 – Am Soc Hematology

Quality of life in MPN comes of age as a therapeutic target RM Scherber, HL Geyer, RA Mesa – Current hematologic malignancy …, 2014 – Springer

Gender differences and MPN symptom burden: An analysis by the MPN quality of life international study group (MPN-QOL ISG). European Hematology Association Annual Meeting Abstracts 2014;Abstract 1039. Geyer HL, Scherber R, Dueck A, et al.

Assessing disease burden in patients with classic MPNs HL Geyer, AC Dueck, RM Scherber… – Mediators of …, 2015 –

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms
RM Scherber, HE Kosiorek, Z Senyak, AC Dueck… – Cancer, 2016 – Wiley Online Library
.
Emerging drugs for the treatment of myelofibrosis HL Geyer, RA Mesa – Expert opinion on emerging drugs, 2015 – Taylor & Francis… Serial use of PRO tools allows clinicians to objectively evaluate the MF symptom burden, compare
efficacy of therapies and adjust medications to improve symptom control.

Gender Differences and MPN Symptom Burden: An Analysis by the MPN Quality of Life International Study Group (MPN-QOL ISG) Geyer, H. Emanuel, R. Dueck, A. Haematologica. 2016 Aug 18. pii: haematol.2016.149559. [Epub ahead of print]

Associations between gender, disease features and symptom burden in the MPN population: An analysis by the MPN QOL International Working Group. Cancer. 2016 Jun 15;122(12):1888-96. doi: 10.1002/cncr.30013. Epub 2016 Apr 12.

The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and  quality of life: An analysis by the MPN QOL International Study Group. Cancer. 2016 Feb 1;122(3):477-85. doi: 10.1002/cncr.29753. Epub 2015 Dec 15.

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms. J Clin Oncol. 2016 Jan 10;34(2):151-9. doi: 10.1200/JCO.2015.62.9337. Epub 2015 Nov 23.

Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease. Mediators Inflamm. 2015;2015:284706. doi: 10.1155/2015/284706. Epub 2015 Oct 11.

Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development. Am J Hematol. 2015 Oct;90(10):864-70. doi: 10.1002/ajh.24098. Epub 2015 Sep 10.

Myeloproliferative neoplasm patient symptom burden and quality of life: evidence  of significant impairment compared to controls. Leuk Res. 2015 Jul;39(7):684-8. doi: 10.1016/j.leukres.2015.04.004. Epub 2015 Apr 17.

Limitations of fibrosis grade as diagnostic criteria for post polycythemia vera and essential thrombocytosis myelofibrosis. Blood. 2014 Jun 12;123(24):3803-10. doi: 10.1182/blood-2013-09-527903. Epub 2014 Feb 19.

Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients. J Clin Oncol. 2012 Nov 20;30(33):4098-103. doi: 10.1200/JCO.2012.42.3863. Epub 2012 Oct 15.

Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. Blood. 2011 Jul 14;118(2):401-8. doi: 10.1182/blood-2011-01-328955. Epub 2011 May2.

The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international  prospective validation and reliability trial in 402 patients. Cancer. 2011 Nov 1;117(21):4869-77. doi: 10.1002/cncr.26129. Epub 2011 Apr 8.

Evaluating the serial use of the Myelofibrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a  JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Leuk Res. 2009 Sep;33(9):1199-203. doi: 10.1016/j.leukres.2009.01.035. Epub 2009 Feb 27.

The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Cancer. 2007 Jan 1;109(1):68-76.

Take me back to the Contents

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Comments on: "Ruben’s Raiders" (2)

  1. What a great article, Zhen, and a testament to how involved patients can make a difference! Thank you. And your loss of Jenny is just heartbreaking. I am so sorry you lost such a good friend.

  2. Bonnie Kaye Evans said:

    Your tribute to Jenny made me cry. No place to leave a comment to express my sorrow. Of how we loved our pets! Jenny was so beautiful.

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