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Living Well

with a Myeloproliferative Neoplasm (MPN)

A Guide for Patients and Caregivers

Dr. Krisstina Gowin

This resource was supported through a sponsorship by Incyte Corporation.

The content of this resource was developed independently from the sponsor.

No part of this book may be reproduced or transmitted in any form or by any means electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the publisher.

This edition is published by

Spry Publishing LLC

315 East Eisenhower Parkway

Suite 2

Ann Arbor, MI 48108 USA

Printed and bound in the United States of America.

10 9 8 7 6 5 4 3 2 1

Paperback ISBN: 9781938170928

Disclaimer: Spry Publishing LLC does not assume responsibility for the contents or opinions expressed herein. Although every precaution is taken to ensure that information is accurate as of the date of publication, differences of opinion exist. The opinions expressed herein are those of the author and do not necessarily reflect the views of the publisher. The information contained in this book is not intended to replace professional advisement of an individual’s doctor prior to beginning or changing an individual’s course of treatment.

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Dedication

In loving memory of Linda Gowin.

Your light continues to shine bright in our hearts.

Acknowledgements

Thank you to my husband and two daughters for

keeping me balanced, inspired, and joyful.

Thank you to Ruben Mesa, M.D. for your ongoing mentorship

and guidance. Your contributions to patients with

myeloproliferative neoplasms are profound and global, and

your vision for the future of medicine is pioneering and innovative.

Contents

Foreword by Dr. Ruben Mesa 6

Introduction 9

Chapter 1: Understanding Myeloproliferative Neoplasms (MPN) 10

Disease Spectrum

The MPN Symptom Burden

Special Topics in MPNChapter 2: Monitoring Your MPN Disease 28

Finding a Specialist

Understanding the Complete Blood Count

Understanding the Bone Marrow Biopsy

When is it Time to Change Treatments?

Monitoring the MPN Symptom BurdenChapter 3: Wellness In MPN – Part One 40

What is Integrative Medicine?

Why is Integrative Health Important in MPN?

Lifestyle: The Backbone of Integrative Health Nutrition ExerciseChapter 4: Wellness In MPN – Part Two 70

Sleep Health

Stress Reduction

Spiritual Care

Rediscovering Joy

The Wellness Plan

Complementary Therapies

Contents

Chapter 5: Managing MPN-Related Symptoms:

An Integrated Approach 84

Fighting Fatigue

Preventing Weight Loss

Controlling Pruritis

Managing Pain

Maintaining Sexual Health

Treating Psychological Health

Addressing Sleep DisordersChapter 6: Getting Quality Care 98

Taking an Active and Informed Role

Getting a Second Opinion

Communicating with Your Healthcare TeamChapter 7: Patient & Caregiver Support 114

Developing a Support System

Important Conversations

Care for the CaregiverResources 132Sources 136Index 146

Foreword

LIVING WELL with a Myeloproliferative Neoplasm (MPN), the title of this wonderful book, summarizes the goal of the author, Dr. Krisstina Gowin, very well. Dr. Gowin has been touched by cancer in her family and took away from that experience the need to bring both more humanity and a holistic approach to cancer care and support. Dr. Gowin, who has long had an interest in improving the care of patients with MPNs—whether essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF)—also studied at the world-renowned Integrative Medicine Fellowship at the University of Arizona under the famous Dr. Andrew Weil on holistic care. She has a personal goal to weave together the best of our standard MPN care, with the most effective integrative medicine techniques, thus achieving balance for MPN patients.

Meanwhile, her goal for this book is to provide a resource for MPN patients, providing essential information along with tools that allow patients and their caregivers to play an active role in the management of their disease. In fact, there is a long history of patients with MPNs working to create a dynamic community for discussion and interactions, advocating for each other, and helping steer and amplify the focus of research on their diseases into meaningful areas. This patient community partners closely with hematology colleagues to advance the understanding and treatment of MPNs—trying many approaches to actively help them live well, despite the limitations of their MPN.

Joyce Niblack, J.D. and Robert Rosen are both exceptional examples of MPN patients who have given generously of their time and talents to advance MPN patients “living well.” Although we have lost both Joyce and Robert to their disease, their call-to-action remains alive and vibrant. Robert Rosen helped develop and found the highly impactful MPN Research Foundation, which proactively has made a huge impact on this field by directing philanthropically-gathered resources to drive research advances in MPNs and advocate on behalf of MPN patients. Joyce Niblack, J.D. broke new ground in developing online patient communities that provide real-time moral and informational support for MPN patients every day. Joyce also helped start the efforts to better understand and impact the difficult symptoms associated with MPNs. Back in 2001, Joyce came to me and shared her view that the symptoms MPN patients face were common and problematic. However, since many MPN patients overall do not look ill, they felt their healthcare providers were not responsive to their symptomatic concerns. The engagement of MPN patients in advocating and determining their own future has only grown from these examples and include many others, such as Antje Hjerpe, David Alexander, Jon Mathias and Zhenya Senyak, to name a few, along with the continued efforts of the MPN Research Foundation.

In response to Joyce’s concerns, as well as other advocates, we conducted the first large scale assessment of MPN symptoms. Leveraging the extensive online community of MPN patients, we conducted a survey of over 1,400 MPN patients and demonstrated symptoms that were both prevalent and sometimes severe, including fatigue, night sweats, itching, headaches, bone pain, and spleen-related problems. We then realized we needed a way to capture and quantify these subjective symptoms to be able to track them (better or worse) in the context of a clinical trial, or even in practice. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF – 27 questions) and shorter version (MPN 10 – 10 items), has helped quantify the symptoms patients with MPN experience. These tools have now gathered data from over 5,000 MPN patients, in over 30 countries, and asked in almost 20 different languages. The data has revealed some key observations, including:

1. MPN patients have frequent symptoms, with fatigue being almost universal.

2. MPN patients suffer a very similar pattern of symptoms regardless of geography or culture; however, culture may impact the severity at which a patient reports those symptoms.

3. Symptoms are overall worst, as a group but not by individual, for patients with MF, then PV, and then ET.

4. Severe symptoms can be present in any MPN subtype, and the severity is not only associated with risk-factor scores (i.e., DIPSS in myelofibrosis or IPSET in ET).

5. Certain symptoms are associated with disease progression, including inadvertent weight loss, fever and bone pain.

6. Monitoring MPN symptoms is important in assessing the impact of any therapy intervention, including phlebotomy or medications.

7. JAK inhibition has perhaps had the greatest impact of any pharmacological therapies on MPN symptoms.

8. Despite the availability of medical therapies, and beneficial impact of JAK inhibition on MPN symptoms, most patients have residual symptoms ranging from mild to problematic.

9. Mr. Senyak (or Zhen as we all know him), who is an MPN patient and advocate, raised the call-to-action regarding the burden of fatigue in MPNs and directly collaborated with our MPN Quality of Life Study Group to understand this burden further.

These observations leave many MPN patients searching for answers on how to help alleviate the problematic symptoms from which they suffer. This book was written explicitly to apply the lessons learned from integrative medicine to tackle unmet needs, including symptoms, in MPN patients.

Living Well is a great choice for focus, as living well or wellness does not imply the absence of disease, but rather balance and achieving the best quality of life (QOL) an individual can attain. Achieving wellness can include working on many aspects of our lives—stress, sleep, nutrition, pain, lifestyle, relationships, and disease understanding—that can improve or worsen an individual’s QOL regardless of the status of their disease. LIVING WELL with a Myeloproliferative Neoplasm (MPN) answers several key questions to help patients achieve that balance:

1. What is the MPN disease spectrum, and how is the disease monitored?

2. What is the background and the elements of integrative medicine?

3. What is the role and benefit of a healthy lifestyle while battling an MPN?

4. What is the information, role, and potential benefits of specific complementary therapies, and how might they help an individual?

I am certain readers will learn many lessons to help them on their journey with their disease. In addition, I suspect that the information presented on healthy lifestyle is relevant to both MPN and non-MPN patients alike.

Finally, I congratulate Dr. Gowin for bringing her passion for holistic patient care of MPN to this wonderful book. Indeed, I think it will be a welcome addition to the library of any MPN patient.

Ruben A. Mesa, M.D.

Director

Mays Cancer Center at UT Health San Antonio MD Anderson – An NCI Designated Cancer Center

Mays Family Foundation Distinguished University Presidential Chair

Professor of Medicine

Introduction

Over recent decades, the wealth and pace of knowledge acquisition surrounding MPNs has been astounding. From the discovery of the JAK V617F gene mutation and the eloquent description of symptom burden, to the development of targeted therapeutics and validated symptom assessment tools, the landscape has truly matured in the field of MPNs.

While these developments are both exciting and hopeful, it continues to be challenging for those afflicted with this disease. Despite recent advances, patients continue to struggle with symptom burden and the chronic nature of the diagnosis of MPN. Many patients seek advice on ways to live better when confronted with a diagnosis of MPN and pursue methods to positively impact their disease and improve quality of life. Simultaneously, an emerging culture of integrative medicine is occurring within cancer care.

Integrative medicine offers the personalized, cutting-edge approach of traditional (allopathic) medical care, while concurrently recommending evidence-based lifestyle medicine and complementary therapies. This new era of integrative medicine is not unique to cancer care and is pervasive in

all aspects of medicine. In fact, I suspect it will be the universal medicine of the future.

With that in mind, it is with great enthusiasm that I offer Living well with a Myeloproliferative Neoplasm to the MPN community. As with all integrative medicine, it begins with a strong foundation in the understanding of the disease spectrum and standard therapies. It then builds on how the MPN patient or caregiver can empower their own health through lifestyle habits and intentional care of the mind, body, and spirit. It is intended as a guide for either patients or caregivers while on their paths to wellness in the face of MPN.

Sincerely,

Krisstina Gowin, D.O.

Chapter 1:

Understanding Myeloproliferative Neoplasms (MPN)

Disease Spectrum

Simply pronouncing mye-lo-pro-lif-er-a-tive neoplasms (MPN) is challenging! It can also be difficult to understand this diagnosis, because it is not a single disease. MPN comprises several specific diseases, including essential thrombocytosis (ET), polycythemia vera (PV), and myelofibrosis (MF). In the simplest of terms, MPNs are a closely-related group of rare blood cancers.

Though MPNs were originally described in the late 1800s (See Sidebar: The History of MPN), it wasn’t until 2005 that several scientists discovered that patients with MPNs share a common gene mutation—the JAK2 mutation—within bone marrow stem cells. Gene mutations or alterations can cause many diseases, including MPN and other forms of cancer.

Our bodies function through a type of internal communications system. JAKs are specific proteins (Janus-associated kinases), which act as signaling mechanisms with cells. In other words, they “tell” blood cells in the bone marrow to divide and grow. When JAKs are working normally, they help the body make the proper amount of blood cells. However, if a mutation is present, the signal malfunctions and stays on permanently.

If you think of JAK genes as a factory, then a mutation flips the “on” switch and leaves the factory in constant production mode, causing too many cells to be manufactured. Just as a factory would eventually have difficulty handling this type of malfunction, the overproduction of cells begins to cause problems within the body, including blood clotting/bleeding, organ enlargement, bone marrow scarring and other symptoms.

Since the JAK2 mutation was discovered, additional gene mutations have been found in MPN patients, including MPL (myeloproliferative leukemia protein) and CALR (calreticulin protein), among others. Although no one knows exactly what causes MPN, most people with the disease have one of these gene mutations. The presence of these mutations helps to diagnose the disease, and with newer techniques, can help us to better understand how the disease may progress, as well as provide a prognosis.

As mentioned, MPNs are a group of linked disorders, and this grouping is referred to as disease spectrum. However, because they are so closely related, they tend to share certain features and there is variability between the individual types of MPN. This means there is the possibility of transformation from one diagnosis to another within the MPN spectrum. For example, someone may be originally diagnosed with essential thrombocytosis (ET), and over time this disease could change into polycythemia vera (PV), with a new set of symptoms. (See diagram.) Let’s look at each diagnosis more closely.

With MPNs, one disease may change into another disease within the spectrum over time.

ET  PV  MF  Acute Myeloid Leukemia (AML)

The History of MPN

This group of blood disorders was originally described in the late 1800’s, a time when medicine and the knowledge of organ systems were in their infancy. In fact, medical practice at that time was very primitive. In 1879, myelofibrosis (MF) was described by a German surgeon named Gustav Heuck as “peculiar blood and bone marrow findings.” More than a decade later, in 1892, Louis Henri Vasquez, a French physician, was the first to describe polycythemia vera (PV). Soon, other renowned physicians began complementing their work and expanding their observations of the disease.

In 1934, essential thrombocythemia (ET) was formally described as hemorrhagic thrombocythemia. They noted similarities and differences between the earlier diagnoses of MPN. Eventually it was William Dameshek, a prolific American-trained physician, who described the group of diseases as myeloproliferative disorders (MPDs), which included PV, ET and MF. He referred to them as “closely related disorders” sharing similar bone marrow findings and patient symptoms.”1 (The name was later changed to myeloproliferative neoplasms or MPN.)

Who was William Dameshek?

William Dameshek (1900-1969) was considered by some as the father of MPNs, although his work was expansive, and he made many other contributions to hematology (the study of blood disorders). He was born in Russia, but moved to the United States at a young age with his parents. He attended Harvard Medical School in Boston, and later was a founder of a medical journal, BLOOD, and served as its first editor-in-chief. BLOOD remains a prestigious medical journal in hematology.

Dameshek was also integral to the formation of the American Society of Hematology (ASH) and served as president of the organization. There is now an annual William Dameshek Prize awarded to individuals who have made outstanding contributions to the field of hematology.

Essential Thrombocytosis (ET)

What is ET?

ET occurs when your body produces too many platelets in the blood. Platelets are “sticky” parts of the blood that help stop bleeding. When a blood vessel in your body is injured and starts to bleed, platelets react by clumping together and forming a blood clot. Obviously, we need platelets to help us stop bleeding, but having too many in the blood can cause abnormal clotting or bleeding. Other symptoms may include headaches, lightheadedness, dizzy spells, changes in vision, burning feeling in hands and feet and more.

There is also the chance of forming a blood clot in a major vessel, such as one that supplies the heart, lungs or brain. If you develop sudden chest pain, shortness of breath, weakness in your face, arm or leg, difficulty speaking or understanding speech, seek urgent medical attention. These may be signs of a serious medical condition.

In rare cases, ET may cause unusual bleeding, such as frequent nosebleeds, easy bruising, bleeding gums or bloody stool. Again, if you experience any abnormal bleeding, it’s important to seek immediate medical attention.

How is ET diagnosed?

ET is an uncommon disorder. It is more likely to be found in people over the age of 50 and slightly more common in women, although young people can still develop ET. If you have a mild form of ET, you may never develop symptoms or require treatment.

In many cases, the first indication that you have ET is the discovery of a blood clot (thrombus). Blood clots can form in any part of the body, but with ET, they occur most often in the brain, hands and feet. The symptoms a person experiences depends on where the clot is located (i.e., if the clot is in the brain, you may develop headaches and/or dizziness, while a clot in the hands or feet may lead to numbness, tingling, redness, throbbing and/or burning pain in the hands and feet).

ET can be diagnosed with a routine blood test, which will reveal an abnormal platelet count. More extensive tests, such as molecular tests or a bone marrow biopsy, may also be ordered depending on your physician. A bone marrow biopsy is done to evaluate changes in the bone marrow that confirm the diagnosis and to rule out other diseases, such as fibrosis (scarring) in the bone marrow.

World Health Organization (WHO) Criteria for Essential Thrombocytosis:

Diagnosis requires meeting all four major criteria or three major criteria and the minor criterion.

Major Criteria	Minor Criterion
Platelet count > 450 x 10°/L	Presence of a clonal marker or absence of evidence for reactive thrombocytosis
Bone marrow biopsy consistent with ET
Not meeting criteria for another MPN
Presence of JAK2 mutation

How is ET treated?

Treatment for ET is based on the severity of the symptoms, which can range from mild to severe. Physicians will also base treatment on your “risk group.” Your risk is determined by your age, your history of blood clots and the presence of the JAK2 mutation. Patients are divided into low, intermediate and high risk. Depending on which group you are in, your healthcare team may recommend no therapy, a daily dose of aspirin (which helps to thin the blood), or drug therapies such as hydroxyurea, interferon, or anagrelide, to help alleviate symptoms and lower your risk of a blood clot.

What is Allele Burden?

MPN patients may hear the term “allele burden” associated with their diagnosis and treatment. An allele is a variant or different form of a specific gene. In MPN, allele burden refers to the proportion of cells that harbor the JAK2 mutation. Although it is not routinely used in clinical practice, some interesting observations have occurred in regard to allele burden. For example, in MF patients who underwent stem cell transplant, achieving a negative allele burden was associated with a decreased risk of recurrence.2 Additionally, allele burden may be helpful in determining the risk of having a thrombotic event (blood clot).3

At this time, the data is still considered controversial, and more study is necessary. Therefore, monitoring allele burden is not currently a standard of care but is sometimes performed at academic medical centers or as part of a clinical trial.

Polycythemia Vera (PV)

What is PV?

Patients with PV have too many red blood cells. In some cases, they may also have too many white blood cells and platelets. Having too many red blood cells can cause the blood to thicken, which makes it more difficult to flow normally through arteries and veins.

Like other forms of MPN, the exact cause of PV is unknown, although evidence suggests that JAKs are involved. In fact, about 95% of all PV patients have a JAK mutation. As discussed, JAK proteins send signals that affect the production of blood cells in the bone marrow. If the JAKs send too many signals, the bone marrow makes too many blood cells, causing PV.

PV affects each person differently. Some patients with PV have no symptoms. In others, PV can be more severe. For example, some patients develop an enlarged spleen. Because the spleen helps your body fight infection and filters unwanted material, such as old or damaged blood cells, the increased number of blood cells caused by PV makes your spleen work harder than normal. This extra work may cause the spleen to get bigger, and lead to abdominal discomfort and feeling full quickly when eating.

Sometimes PV is discovered after a blood clot occurs and your healthcare providers are looking for the cause. Much like ET, the most worrisome complication is blood clots in major vessels, such as in the heart, lungs or brain.

In a very small percentage of people, PV leads to other blood diseases, such as myelofibrosis (MF), a disease in which scar tissue develops in the bone marrow, or leukemia.

PV is most commonly diagnosed in men over the age of 60, but can occur in both men and women of any age.

In addition to elevated red and white blood cells and platelets, general symptoms of PV may include (but are not limited to):

• Elevated LDH (an enzyme found in cells)

• High blood pressure

• Enlarged spleen or liver (along with abdominal discomfort or the sensation of feeling full quickly)

• General skin itchiness (pruritis), which may be worse when taking a shower

• Redness of hands and feet (erythromelagia)

• Blood clots

• Hemorrhage

• Facial redness

• Gout or arthritis

• Fatigue

• Psychosocial symptoms (depression, anxiety, etc.)

• Sleep disturbance

• Dizziness

• Headache

How is PV diagnosed?

PV can be diagnosed by:

• A blood test which looks at blood “counts,” including the number of red blood cells, white blood cells and platelets.

• Molecular tests (done on the blood or with a bone marrow biopsy to determine gene mutations)

• Bone marrow biopsy to evaluate if there are changes in bone marrow that confirms the diagnosis or rules out other diseases, especially the possibility of fibrosis (scarring) in the bone marrow, which may change treatment decisions or prognosis.

• A blood test to look at erythropoietin level, or “EPO” level. Erythropoietin is a protein that stimulates red blood cell production in the bone marrow. EPO levels should be normal or low in PV. If the level is high, then other causes, such as lung disease, smoking, sleep apnea or high altitude, should be considered.

World Health Organization (WHO) Criteria for Polycythemia Vera:

The diagnostic criteria for PV were updated in 2016, with two major changes: the hemoglobin (a part of the blood that transports oxygen) threshold was lowered to 16.5 g/dl, and a bone marrow biopsy is now considered a major component for diagnosis.

A diagnosis of PV requires meeting all three major criteria or two major criteria and the minor criterion.

Major Criteria	Minor Criterion
Hemoglobin > 16.5 g/dl in women or hematocrit >49% in men; >48% in women or increased red cell mass (RCM)	Low level or normal blood erythropoietin (EPO) level
Bone marrow biopsy showing changes consistent with PV
Presence of JAK2 V617F or JAK2 exon 12 mutation

How is PV treated?

PV is a chronic and sometimes progressive disease, which means it may get worse over time. However, PV can be managed by keeping blood counts under control. Like ET, understanding your risk for events such as heart attack and stroke is important when determining treatment. High risk factors include being 60 years of age or older and having a history of blood clots, heart attack or stroke.

For patients who are considered “low risk,” treatment often consists of removing blood (phlebotomy). Your healthcare team will monitor your blood counts, and if hematocrit levels (the volume of red blood cells) get too high (>45%), a phlebotomy is recommended. The frequency of this procedure will depend on your disease and your physician’s treatment plan. In addition, a daily aspirin is often recommended, depending on your medical history, and should be discussed with your doctor.

Other therapies may be considered, such as hydroxyurea, interferon, ruxolitinib, piprobroman, and related drugs, if you are considered high risk for a thrombotic event (blood clot).

What is the magic of the 45% or less

hematocrit goal?

A study was performed (Cyto PV study published by Marchioli et al) which revealed that patients who had phlebotomy (blood removal) with a hematocrit goal higher than 45% had a 4x increase in cardiovascular death or thrombosis (blood clot). Be sure you are hitting the proper goal, and discuss with your physician if your hematocrit level is higher than 45%.

Making Your Phlebotomy Easier

Removing blood can be stressful for some people. To make things easier, be sure to drink plenty of water the day before your phlebotomy. Staying hydrated is important because it helps decrease dizziness by keeping the blood volume as normal as possible before removing it. Hydration also helps the veins “plump,” which makes it easier to find a vein that can easily be punctured, Additionally, try to limit caffeine on the day prior to a blood draw, as it acts as a mild diuretic and increases the amount of urine you produce, which may lead to dehydration.

It’s also important to practice gentle breaths during the procedure. Some people hold their breath in anticipation of the needle poke, but this can make you feel faint. You’ll be far less likely to feel lightheaded if you continue to breath normally. If the potential for pain is making you nervous, or you are particularly sensitive, you can ask the phlebotomist who is performing the procedure to use a numbing medication.

If you have had problems in the past, such as fainting or difficulty finding a vein, be sure to tell your infusion nurse or doctor prior to the procedure.

During the procedure, be sure to sit still and don’t watch the blood drain if you know it makes you queasy or lightheaded. Try thinking of something pleasant or singing a song in your head, which takes the focus off the procedure.

Once the procedure is complete, take a moment before standing up. Rise slowly and make sure you are not dizzy or lightheaded before starting to walk. Usually, resting for a few minutes and drinking water prior to standing up helps to decrease dizziness after your phlebotomy procedure.

Myelofibrosis (MF)

What is MF?

Similar to ET and PV, myelofibrosis involves the abnormal production of blood cells. However, MF is a chronic blood cancer in which the bone marrow function is impacted by scarring, producing blood counts that are either too high or too low. In fact, myelo means “bone marrow” and fibrosis means “scarring.”

As we discussed earlier, although no one knows exactly what causes MF, we do know that JAKs (Janus-associated kinases) are involved. Remember, JAKs tell blood cells in the bone marrow to divide and grow. When JAKs are working properly, they help the body make the right number of blood cells. However, when these proteins are malfunctioning, they cause the body to produce the wrong number of cells, which can lead to bone marrow scarring and an enlarged spleen, among other symptoms.

In its very early stages, MF may produce no symptoms. However, as the disease progresses, the signs and symptoms typically begin to increase. Symptoms of MF can range from mild to severe and may include (but are not limited to):

• Low red blood cells

• High or low white blood cells or platelets

• Enlarged spleen or liver (and abdominal pain or feeling full quickly after

a meal)

• Fever

• Night sweats

• Bone pain

• Fatigue (which may be debilitating)

• Itchiness (pruritis)

• Blood clots (thrombotic events)

• Psychosocial symptoms (depression, anxiety, etc.)

• Sleep disturbance

Patients with MF often have too many cytokines, which are proteins that cause inflammation. An overproduction of cytokines may cause itching, night sweats, and bone and muscle pain.

How is MF diagnosed?

MF is most commonly seen in men and women over the age of 60. Approximately 85% or more of people with MF have an enlarged spleen at diagnosis. If your bone marrow is not making enough blood cells or making them too quickly so they don’t have time to fully form, the spleen takes over and begins to make and dispose of blood cells. As it works harder, it becomes larger, causing patients to feel abdominal discomfort, pain under the left ribs and/or early feelings of fullness.

The tests used to diagnose MF are similar to those used in ET and PV, including:

• A blood test to evaluate blood counts (red blood cells, white blood cells and platelets)

• Molecular tests (done on blood or with a bone marrow biopsy)

• Bone marrow biopsy, which is essential to diagnose MF. The bone marrow is viewed under a microscope to see cellular changes consistent with MF, as well as to determine how much scarring or “fibrosis” is present. This will be graded on a scale of 1 to 3, with 3 being the most fibrotic or scarred bone marrow.

Other factors can be considered when making a diagnosis of MF, such as an enlarged spleen, changes in appearance of blood cells under a microscope, or changes in routine blood tests, such as higher LDH levels.

World Health Organization (WHO) Criteria for Myelofibrosis:

A diagnosis of MF requires meeting all three major criteria, and at least one minor criterion.

Major Criteria	Minor Criterion
Presence of megakaryocytic proliferation and atypia, accompanied by:• Fibrosis• Not meeting WHO criteria for other blood diseases• Presence of JAK2, CALR, or MPL mutation or other marker	Presence of at least one of the following, confirmed in two consecutive tests:• Low red blood cells not attributed to another condition• High white blood cell count• An enlarged spleen• Changes in appearance of cells under a microscope that are consistent with MF

How is MF treated?

The only curative treatment for MF is an allogeneic stem cell transplant, which involves transferring the stem cells from a healthy person (the donor) to the patient’s body after high-intensity chemotherapy or radiation. This can be a high-risk procedure. The intense doses of chemotherapy or radiation are used to inactivate the immune system to reduce the chance of cell graft rejection and enable donor cells to travel to the bone marrow. However, because this treatment temporarily shuts down the immune system, there can be adverse reactions.

In the last decade, targeted therapy with Janus kinase (JAK) inhibitors has become available for treatment. This therapy can improve symptoms by inhibiting or slowing down the overproduction of blood cells, thereby decreasing the size of the spleen. This treatment may also prolong a patient’s life.

Many other medical therapies are often used to treat MF, depending on a patient’s symptoms and the treating physician. For example, agents such as erythropoietin can be used to stimulate red blood cell count. Patients may also receive transfusions, steroids, or immunomodulating agents.

In addition, many clinical trials are ongoing for patients with MF, and you are encouraged to talk to your healthcare team about which trials may be available to you.

The MPN Symptom Burden

As an MPN patient, you may experience a wide range of symptoms which can impact your quality of life (QOL). The symptoms associated with MPN, and the severity of those symptoms, can differ greatly from one person to another. Keeping track of how symptoms affect you day-to-day, ideally with a symptom diary (see Chapter 6), is the best way to monitor and treat the disease. That way, you can discuss any changes in symptoms with your healthcare team at each visit. Understanding your individual symptoms is very important to managing the disease and reducing its effects.

To help us better understand this burden of symptoms, as well as how physicians evaluate and manage the disease, the MPN QOL group was formed. The group is a collaborative effort between UT Health – San Antonio, Mayo Clinic Arizona, Arizona State University and the University of Arizona. They are dedicated to advancing our knowledge of MPN symptom burden, quality of life, and interventions to improve MPN patient wellness.

Obviously, having a better understanding of the variety of symptoms patients with MPN experience is important for developing effective treatments. In 2007, an international internet-based study of 1,179 patients was conducted for this purpose. The goal of the study was to look beyond blood counts and gene mutations, to learn what MPN patients actually experience. Questions centered around how the disease was impacting day-to-day life for patients. This Landmark Study found that symptoms were often debilitating and occurred frequently among respondents.

Specifically, the study uncovered the following:

Symptom % of respondents who experienced this symptom

Fatigue >80%

Pruritis (itchiness) 52.2%

Night sweats 49.2%

Bone pain 43.9%

Fever 13.7%

Weight loss 13%

In 2011, a unique symptom assessment tool, the MPN Symptom Assessment Form (MPN SAF), was developed (see Chapter 2), allowing for sensitive and standardized symptom evaluations for those living with MPN. The results of this international validation study, involving 402 patients, again revealed that MPN-associated symptoms were severe and frequent.

Like the earlier study, patients noted that fatigue was the most common symptom (93%) and was often debilitating. Additional symptoms were both physical and psychological in nature, including:

Decreased quality of life 84%

Insomnia 65%

Sad mood 65%

Sexuality problems 58%

Night sweats 56%

Bone pain 49%

Headache 48%

Cough 46%

Abdominal pain 46%

Weight loss 35%

Fevers 20%

Within the disease spectrum, those diagnosed with MF experienced the most symptoms.

Since these studies were conducted, a shorter version of the symptom assessment tool was developed to make it quicker and easier to use for both patients and physicians. This 10-item MPN Total Symptom Score (TSS) form is now routinely used to assess MPN symptom burden and is part of the recently developed National Cancer Care Network (NCCN) guidelines (see http://www.nccn.org). The impact on symptom burden, as measured by the MPN TSS, is used to gauge how well treatments are working and help catch and manage early progression of the disease.

Special Topics In MPN

When you are diagnosed with any form of MPN, there are some associated health issues you should be aware of, including:

1. Thrombotic events (blood clots) – A serious complication of MPN is the possibility of a blood clot in a major artery to the brain (stroke), heart (heart attack) or lungs (pulmonary embolism) or other areas. This risk for thrombotic events increases with other factors, such as age, blood pressure, obesity, smoking and a prior history of these events. If a thrombotic event occurs, several new considerations will be discussed between you and your healthcare team.

For instance, if you were not receiving treatment for your MPN previously, a thrombotic event will likely trigger a course of treatment. Remember, having a history of blood clots places you at a high risk for another thrombotic event in the future.

2. Bleeding – Although it may seem counterintuitive to what we’ve discussed about MPNs and the risk of blood clotting, abnormal bleeding can also occur with MPNs. This occurs most often in those with ET, who have very high platelet counts. As the number of platelets increase, they may “consume” a factor required for blood clotting. This is called the Von Willebrand Factor, and it can lead to an increased risk for bleeding. Sometimes healthcare providers will do a blood test to check the “Von Willebrand factor activity level” to help evaluate the risk of bleeding. The results may impact treatment decisions, such as avoiding aspirin therapy, or change a decision to undergo elective surgical procedures.

3. Surgery – Before you plan any surgical procedure, it’s important for MPN patients to have a thoughtful, thorough discussion with your surgeon and hematologist regarding your risk for blood clots or bleeding. It may be best to delay a procedure until your disease has been optimized to decrease your risk. Often, surgical procedures will require the use of anti-coagulants post operatively, and again, the risks and benefits should be discussed with your healthcare team.

4. Allogeneic Stem Cell Transplant – Hematopoietic stem cell transplant is the only curative treatment for MPNs. Given the high-risk nature of this procedure and potential for complications, it’s typically reserved for intermediate or high-risk myelofibrosis patients only. It’s a rigorous procedure, which requires a consultation with a stem cell transplant specialist to evaluate if it’s the right treatment approach for you. The evaluation typically includes age, functional status, presence of other diseases, health of major organ systems, psychological status, the availability of a caregiver, and other considerations. If you have intermediate or high-risk MF, ask your healthcare team if a transplant consultation is appropriate.

Julianne’s Story

At 55, Julianne was surprised by a heart attack. Fortunately, she received prompt treatment and recovered from the event.

“Although no one wants to have a heart attack, I was grateful that it wasn’t more serious, and felt like I got a second chance at life,” remembered Julianne. “I was determined to make the most of it.”

However, during the next several years, Julianne felt constantly fatigued and complained of feeling itchy all the time. She took antihistamines for the itchiness and initially thought the tiredness was a lingering result of the heart attack. Finally, at age 58, a bone marrow biopsy confirmed a diagnosis of ET.

Once she began seeing a hematologist and receiving treatment, which included a daily aspirin and hydroxyrea, her symptoms improved.

“I was so relieved to find out that my fatigue wasn’t something I just had to live with,” said Julianne. “And the itchiness, which was driving me crazy, was completely gone. I felt like I got my life back, again.”

Unfortunately, about eight years later, Julianne began experiencing new symptoms. She started to feel full quickly when eating and developed stomachaches after meals. Julianne also suffered from nightly fevers and sweats. Eventually, she started losing weight and became alarmed. She quickly made an appointment with her hematologist.

“My hematologist recommended a repeat bone marrow exam to see if my disease had progressed to myelofibrosis,” recalled Julianne. “I never knew that my disease could change like that, but I learned that MPNs can transform over time.”

Julianne was diagnosed with myelofibrosis (MF) and began a new therapy. Thankfully, she improved quickly and has been able to effectively manage her symptoms for many years. Of course, she is regularly monitored by her healthcare team to keep symptoms in check and monitor disease progression.

1Tefferi, A. The history of myeloproliferative disorders: before and after Dameshek. Leukemia. 2008;22(1):3-13.

2Lange et al. JAK2 p.V617F allele burden in myeloproliferative neoplasms one month after allogenic stem cell transplantation significantly predicts outcome and risk of relapse. Haematologica. 2013 98(5):72-8 Epub 2013 Jan 8.

3Austin SK, Lambert JR, et al. The JAK2 V617F mutation and thrombosis. Br J Haematol. 2008; 143(3):307; or to estimate risk of evolution to post ET/PV myelofibrosis. Alvarex-Larran, et al. JAK2 V617F; monitoring in polycythemia vera and essential thrombocythemia: clinical usefulness for predicting myelofibrotic transformation and thrombotic events. Am J Hematol. 2014;89(5):517.

www.mpn-qol.org

Chapter 2:

Monitoring Your Mpn Disease

Monitoring Your MPN Disease

Being diagnosed with a rare blood cancer is life changing for both you and your loved ones. It can be a confusing and emotional time as you begin to deal with your “new reality.” In fact, newly diagnosed patients often compare the emotional experience to the five stages of grief – denial, anger, bargaining, depression and acceptance. As difficult as it may seem, working through these stages can help you deal with your diagnosis.

Coping with illness is an ongoing process, filled with twists and turns and unknown paths. Learning as much as possible about your disease, working with a specialist, and getting support are the best ways to navigate this journey.

It’s also very important to accurately monitor your disease, which will help you advocate for yourself, stay on track with treatments, and improve outcomes. Although there are no known cures for MPN, many people who have ET, PV or MF can effectively manage symptoms and enjoy longevity with proper monitoring and treatment.

Finding a Specialist

The first step in getting quality care is to find a hematologist specializing in MPNs. Because MPNs are rare diseases with unique symptoms and treatment options, it’s essential to find a specialist who understands the needs of MPN patients. However, the rarity of MPNs can also make it more challenging to find a specialist. Your primary healthcare provider may be able to refer you to an MPN specialist, but be prepared to do some of your own research.

Some additional places to find a specialist include:

• The American Society of Hematology, which offers a convenient search tool to help you find treatment facilities by region and specialty. Visit: http://www.hematology.org/Patients/FAH.aspx, and go to “Find a Specialist.”

• The MPN Forum, which provides a list of patient-recommended hematologists who specialize in MPNs. Visit: https://mpnforum.com/list-hem/.

Questions to Ask Your Hematologist

• How many MPN patients do you treat now?

• What is my exact diagnosis?

• Did I test positive for any mutations? What kind of genetic testing can you offer me?

• What is my plan for managing this in the short and long term?

• What treatments am I a good candidate for, and why?

• What are the side effects of my treatment options?

• What kind of lifestyle changes should I make to deal with symptoms?

• If you are of childbearing age, how should I manage my family planning?

• How should I tell my immediate family about how this will affect my life and theirs?

• What kinds of clinical trials, if any, am I qualified for?

Source: MPN Research Foundation

Understanding The Complete Blood Count

One of the two major components used to monitor MPN is the complete blood count. The body is primarily made up of water and cells. While some cells stay in place to form tissues and organs, such as muscles or the heart, others may circulate around within the blood. The major blood cells include red blood cells, white blood cells and platelets. Since blood cells play a critical role in MPN progression and treatment, these cells are routinely monitored in MPN patients.

Specifically, changes in the blood cells can help determine if treatments are working and what doses are correct for you. Blood cell counts can also indicate if your disease is progressing to a more advanced form of MPN.

Blood counts are evaluated by a blood test called the complete blood count, or CBC. Let’s take a look at the components of the CBC:

White Blood Cell (WBC) Count

There are several types of white blood cells, which help your body fight infections. The most important infection fighters are white blood cells called “neutrophils.” With a CBC, your neutrophils will be counted and reported as the “absolute neutrophil count” or ANC. If your neutrophils are low, then you have what is called “neutropenia.”

Neutropenia (low white blood cell count) leaves you more susceptible to infections. The lower your ANC is, the more likely you are to have health problems:

• If your ANC is lower than 1,000, then you have a higher risk of getting an infection.

• If your ANC is lower than 500, then you have a higher risk of getting a more serious infection.

If you are diagnosed with neutropenia, it’s important to take steps to avoid germs and prevent opportunities for infection. (See Sidebar: Avoiding Infections)

Avoiding Infections

The following tips will help you steer clear of germs and stay safe while your white blood cell count is low:

• Wash your hands often, including before and after you eat, when using the bathroom, after coughing, sneezing and blowing your nose, after shaking someone’s hand or touching anything handled by others.

• Take a shower or bath every day.

• If your skin gets dry, use unscented lotion or oils. This will help prevent your skin from cracking, which can let in germs.

• If you cut or scrape yourself, clean the area with soap and warm water right away. Then cover it with a bandage.

• Always wear shoes in the hospital and around the house, and especially outdoors.

• Rinse your mouth out with water after you eat and before you go to bed.

• Use an ultra-soft toothbrush, and only floss your teeth if your ANC is higher than 500 and your platelet count is 50,000 and higher.

Avoiding Infections (Cont.)

• Use lip balm (like ChapStick) to prevent drying and cracking.

• If you wear dentures, make sure they fit well to avoid irritation.

• Check with your doctor before you see the dentist.

• Ask someone else to clean around the house, especially litter boxes, birdcages and fish tanks.

• Do not touch fresh flowers, houseplants, dirt or soil, or stagnant (still) water, and do not keep any plants in your home—not even dried flowers. Ask your doctor about when it is safe to have plants or flowers near you.

• Avoid crowded places and stay away from people who are sick.

• Never swim in lakes, ponds, rivers or oceans. If you want to swim, talk it over with your doctor or nurse first, and swim only in a pool that is treated with chlorine to kill germs. Also, stay out of hot tubs and Jacuzzis.

• Keep away from construction sites, since germs can hide in dirt and dust.

• Use an electric shaver instead of a razor, and do not get a manicure, pedicure or fake nails (or nail tips).

• Prevent cuts and tears in your rectum by avoiding enemas, rectal thermometers or suppositories (medicines that you put in your anus).

• Women need to avoid tampons, vaginal suppositories (like those used to treat a yeast infection), and douches.

• Be sure not to get any vaccines (like a flu shot) unless your doctor tells you to.

• Use a water-based lubricant during sex.

• Avoid anal sex. It is more likely than vaginal sex to cause cuts and tears.

Source: National Institute of Health – www.cc.nih.gov/ccc/patient_education/pepubs/cbc.pdf

Red Blood Cell (RBC) Count

Red blood cells carry oxygen and remove waste from your body. These cells also contain a protein called hemoglobin, which is what makes red blood cells the color red.

Hemoglobin (HGB) Value

Hemoglobin carries oxygen from your lungs to the rest of your body. It also moves carbon dioxide (waste) to your lungs so you can breathe it out.

Hematocrit (HCT) Value

The hematocrit value measures how much of your total blood count is made up of red blood cells.

Platelet Count

Platelets help stop bleeding by sticking together to form blood clots, which “plug” cuts and wounds.

Understanding the Bone Marrow Biopsy

The second major component used to monitor MPN is bone marrow. The bone marrow is the blood cell factory of the body, producing red cells (oxygen carrying cells), white blood cells (infection fighting cells), and platelets (blood clotting cells). As we’ve discussed, in MPN this “factory” malfunctions, producing too many cells or is hindered by scarring (fibrosis). Therefore, your healthcare team will likely want to look at your bone marrow under the microscope to better understand your disease.

To do this, the team will have to take a sample of your bone marrow. This process is called a “bone marrow biopsy.” Bone marrow biopsies are often performed when your disease is first being diagnosed to confirm the diagnosis and determine the severity of the disease. Later in the course of MPN, a bone marrow biopsy is often used to monitor and evaluate if your MPN is becoming more advanced.

The Bone Marrow Biopsy Procedure

A bone marrow biopsy can be done in a hospital or clinic by your healthcare team. It’s typically a short procedure, lasting only 10 minutes or so. Unless there are complications, which are rare, you will go home the same day. Many bone marrow biopsies are performed with only local numbing medications, which will not cause difficulty in driving. However, in some cases, your team may decide to use medication to decrease your anxiety of pain, and in that case, you will need someone to drive you home.

Before the Procedure:

• You will likely discuss the risks and benefits of the procedure and be required to sign an informed consent document that you understand these risks and benefits.

• Just prior to the procedure, the team will check your vital signs, and you may be given some medication to relax you.

• The area where the physician will insert the biopsy needle is marked and cleaned. The bone marrow fluid (aspirate) and tissue sample (biopsy) are usually collected from the top ridge of the back of a hipbone (posterior iliac crest). Sometimes the front of the hipbone may be used.

• You’ll be asked to lie on your abdomen or side, and your body will be draped with a cloth so that only the exam site is showing.

The Procedure

• The bone marrow aspiration is usually done first. The doctor makes a small incision, then inserts a hollow needle through the bone and into the bone marrow.

• Using a syringe attached to the needle, the doctor withdraws a sample of the liquid portion of the bone marrow. You may feel a brief sharp pain or stinging. The aspiration only takes a few minutes. In some cases, several samples may be taken.

• Next, the physician uses a needle to withdraw a sample of solid bone marrow tissue.

After the Procedure

• Pressure will be applied to the area where the needle was inserted to stop the bleeding. Then, a bandage will be placed on the site, and you will be asked to rest for a few minutes.

• If you received medications, a driver will take you home, and you are advised to relax for the remainder of the day. If you did not receive medications, then you may return to your normal routine.

• You may feel some tenderness for a week or more after your bone marrow biopsy. Ask your physician about taking a pain reliever, such as acetaminophen (e.g., Tylenol and others).

It’s important to contact your physician if you have:

• Bleeding that soaks through the bandage or doesn’t stop with direct pressure.

• A persistent fever.

• Worsening pain or discomfort.

• Swelling at the procedure site.

• Increasing redness or drainage at the procedure site.

When Is It Time to Change Treatments?

As discussed, monitoring your disease is essential for evaluating treatments. Are they working effectively to manage symptoms? Do dosages need to be changed? Is disease progression being controlled? Is it time to change therapies?

It can be difficult to understand why new treatments are being suggested by your healthcare team, especially if you feel fine on your current course of treatment. By understanding the reasons for changing therapies, you may feel more comfortable with the new treatment being recommended.

There are a number of primary reasons why your healthcare team may recommend a change in therapy, including:

• Your risk group has increased either by you getting older or by new developments in your health (such as a new blood clot, heart attack or stroke).

• You are experiencing side effects from your current therapy.

• Your blood counts are poorly controlled on your current therapy.

• Your symptoms are poorly controlled on your current therapy.

• Your spleen is increasing in size.

• Your disease has advanced. As previously mentioned, MPNs are not distinct clinical entities, but rather a group of linked disorders. Therefore, there is a possibility of transformation from one diagnosis to another within the MPN spectrum. For example, a patient initially diagnosed with ET may develop post-ET myelofibrosis.

(Note: There may be other reasons for changing therapies than those listed here. Any change in treatment should involve a thorough discussion with your healthcare provider.)

While changing treatments may cause some anxiety, a thoughtful and thorough discussion with your healthcare team about the reasons for the change should help to ease your uncertainty. (See Chapter 6 for tips on communicating with your healthcare team.)

Monitoring the MPN Symptom Burden

Remember, as an MPN patient you may experience a wide range of symptoms which can impact your quality of life. Keeping track of how symptoms affect you day-to-day, ideally with a symptom diary (see Chapter 6), along with an MPN symptom assessment form (SAF) (see below), is the best way to monitor and treat the disease. By accurately tracking symptoms, you can discuss any changes with your healthcare team at each visit, allowing them to more effectively manage the disease and reduce its effects.

Talk to your healthcare provider about the MPN SAF, and discuss how frequently you should be performing the assessment. Always remember to bring your MPN SAF forms and symptom diary to your office visits with your healthcare team. Your symptom information will be critical to making decisions regarding your treatment and detecting advancing disease early in its course.

Myeloproliferative Neoplasm Symptom Assessment Form (Mpn-Saf)1

(Recommended for assessment of symptom burden initially; then you may use the short version.)

Circle the one number that describes, during the past week, how much difficulty you have had with each of the following symptoms:

Living Well with a Myeloproliferative Neoplasm (MPN)

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