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Myelodysplastic
Syndromes
Presented with support from
Myelodysplastic Syndromes
NCCN Foundation gratefully acknowledges support from the following individuals
An additional fifty-five (55) donations were received from other NCCN staff members.
Myelodysplastic
Syndromes (MDS)
Learning that you have cancer can be overwhelming. The goal of this book is
to help you get the best cancer treatment. It explains which cancer tests and
treatments are recommended by experts in myelodysplastic syndromes.
NCCN aims to improve the care given to patients with cancer. NCCN staff work with experts to create helpful programs and resources for many
stakeholders. Stakeholders include health providers, patients, businesses, and others. One resource is the series of books for patients called
the NCCN Guidelines for Patients. Each book presents the best practice for a type of cancer. The patient books are based on clinical practice
guidelines written for cancer doctors. These guidelines are called the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Clinical
practice guidelines list the best health care options for groups of patients. Many doctors use them to help plan cancer treatment for their patients.
Panels of experts create the NCCN Guidelines. Most of the experts are from NCCN Member Institutions. Panelists may include surgeons,
radiation oncologists, medical oncologists, and patient advocates. Recommendations in the NCCN Guidelines are based on clinical trials and the
experience of the panelists. The NCCN Guidelines are updated at least once a year. When funded, the patient books are updated to reflect the
most recent version of the NCCN Guidelines for doctors. For more information about the NCCN Guidelines, visit NCCN.org/clinical.asp.
NCCN staff involved in making the guidelines for patients and doctors include:
Endorsed by
The MDS Foundation, Inc. The Leukemia & lymphoma society (LLS)
The MDS Foundation, Inc. is pleased to endorse the NCCN Patient LLS is dedicated to developing better outcomes for
Guidelines: Myelodysplastic Syndromes (MDS) as an instrumental blood cancer patients through research, education and
resource to patients with MDS and caretakers. Providing a guide in patient services and is happy to have this comprehensive
a patient-friendly format offers patients access to understandable resource available to patients with MDS.
information and knowledge to assist them in making important www.LLS.org/informationspecialists
decisions about their care. www.mds-foundation.org
The NCCN Foundation supports the mission of the National Comprehensive Cancer Network (NCCN)
to improve the care of patients with cancer. One of its aims is to raise funds to create a library of books for
patients. Learn more about the NCCN Foundation at NCCN.org/foundation.
2016 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines for Patients and illustrations
herein may not be reproduced in any form for any purpose without the express written permission of NCCN.
Myelodysplastic
Syndromes (MDS)
4 How to use this book 63 Part 6
Making treatment decisions
5 Part 1 Offers tips for choosing the best treatment
MDS basics for you.
Explains how and where this type of
cancer starts. 73 Glossary:
74 Dictionary
15 Part 2 79 Acronyms
Testing for MDS
Describes the tests used to confirm this 82 NCCN Panel Members
type of cancer and plan treatment.
83 NCCN Member Institutions
25 Part 3
Prognostic scoring and risk 84 Index
groups
Describes how doctors rate and classify
the severity of MDS to help plan treatment.
31 Part 4
Overview of MDS treatments
Describes the types of treatments that may
be used to control MDS and its symptoms.
45 Part 5
Treatment guide
Presents treatment options based on the
risk group and symptoms.
Who should read this book? The recommendations in this book are based on
science and the experience of NCCN experts.
The information in this book is about However, each patient is unique and these
myelodysplastic syndromesa group of cancers recommendations may not be right for you. Your
in which the bone marrow doesnt make enough doctors may suggest other tests or treatments
healthy, mature blood cells. Patients and those based on your health and other factors. If other
who support themcaregivers, family, and suggestions are given, feel free to ask your
friendsmay find this book helpful. It may help treatment team questions.
you discuss and decide with your doctors what
care is best.
Figure 1.1
Blood cells in bone marrow
Bone marrow is the soft, sponge-like tissue in the center of most bones. Blood stem cells in the
bone marrow make all types of blood cells.
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
What is MDS?
Cancer is a disease of cells. MDS (myelodysplastic of DNA (deoxyribonucleic acid). DNA is grouped
syndromes) is a group of cancers that affect blood together into long strands called chromosomes. See
cells in the bloodstream and bone marrow. MDS Figure 1.2. Changes (mutations) in genes can cause
starts in the blood-forming cells (blood stem cells) of normal cells to become cancer cells. Exactly what
the bone marrow. causes the gene changes is not known.
Normal blood stem cells grow and then divide to MDS happens when changes in genes cause blood
make new red blood cells, white blood cells, and stem cells to become abnormal. This damages the
platelets as the body needs them. When the cells blood stem cells and bone marrow so they dont work
grow old or get damaged, they die. New blood cells as well as they should. The abnormal blood stem
are then made to replace the old ones. cells have trouble making enough new blood cells for
the body. They also make new blood cells that are
Inside of all cells are coded instructions for building abnormal (defective).
new cells and controlling how cells behave. These
instructions are called genes. Genes are a part
Figure 1.2
Chromosomes and genes in cells
Genes are coded instructions in cells for making new cells and controlling how cells behave.
Genes are a part of DNA, which is bundled into long strands called chromosomes. Every cell has
23 pairs of chromosomes.
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
The defective blood cells are different from normal MDS may continue to get worse over time. In a small
blood cells in a few key ways: number of cases, it may progress to a fast-growing
(aggressive) cancer called AML (acute myeloid
The cells have an abnormal size, shape, or leukemia). This can happen as more and more blast
look (appearance). This is called dysplasia. cells fill up the bone marrow. However, most patients
The cells do not grow into normal, mature with MDS do not develop AML.
blood cells and do not leave the bone marrow
as they should.
The cells may remain immature, as blast cells,
and not leave the bone marrow.
The cells may die too early in the bone
marrow or soon after they enter the
bloodstream.
What are the types of MDS? MDS subtypes in the WHO classification
system
MDS is divided (classified) into smaller groups based
on certain features of the bone marrow and blood MDS-UD
cells. These smaller groups are called subtypes. (MDS with unilineage dysplasia)
There are two systems that can be used to classify In this subtype, there is a low number of one type
the MDS subtypes. of blood cells in the bloodstream. The same type of
blood cells looks abnormal in the bone marrow. For
The first one was created in 1982 and is called the the affected cell type, at least 10 percent of the cells
FAB (French-American-British) classification system. look abnormal (show dysplasia). No blast cells are
The FAB system groups MDS into five subtypes. found in the bloodstream. Less than 5 percent of cells
This system is not used much today. The newer in the bone marrow are blast cells.
one is called the WHO (World Health Organization)
classification system. The 2016 Revision to the WHO MDS-RS
system groups MDS into seven main subtypes. The (MDS with ring sideroblasts)
WHO system also has a category called MDS/MPN In this subtype, there is a low number of red blood
(myelodysplastic/myeloproliferative neoplasms) with cells in the bloodstream. Red blood cells are also
four other subtypes. abnormal in the bone marrow. At least 15 percent of
young red blood cells in the bone marrow are ring
The WHO system is most commonly used today. sideroblasts. Less than 5 percents of cells in the bone
Most doctors use this system to diagnose MDS and marrow are blast cells. No blast cells are found in
classify MDS subtypes. The main factors that are the bloodstream. There is a normal number of white
used to define the MDS subtypes in the WHO system blood cells and platelets in the bloodstream and these
include: cells look normal in the bone marrow.
MDS-EB1 MDS-EB-T
(MDS with excess blasts-1) (MDS with excess blasts in transformation)
In this subtype, one or more types of blood cells are In this subtype, the number of blast cells is much
low in the bloodstream and also look abnormal in the higher than normal. In the bloodstream, 5 to 19
bone marrow. The number of blast cells is slightly percent of cells are blast cells. In the bone marrow,
higher than normal. Less than 5 percent of cells in 20 to 30 percent of cells are blast cells. One or more
the bloodstream are blast cells. In the bone marrow, 5 types of blood cells are low in the bloodstream and
percent to 9 percent of cells are blast cells. also look abnormal in the bone marrow. (Please
note: This subtype is no longer included in the WHO
MDS-EB2 classification of MDS. But, NCCN experts suggest
(MDS with excess blasts-2) that this subtype be treated as MDS or AML based on
In this subtype, one or more types of blood cells are certain factors. Thus, MDS-EB-T is still included as
low in the bloodstream and also look abnormal in the a subtype of MDS in this book and in the treatment
bone marrow. The number of blast cells is higher than guidelines written for doctors.)
normal. Five to 19 percent of cells in the bloodstream
are blast cells and 10 to 19 percent of cells in the
bone marrow are blast cells.
MDS-U
(MDS, unclassified)
In this subtype, the features of the blood and bone
marrow dont fit any of the other subtypes. One or
more types of blood cells are low in the bloodstream,
but less than 10 percent of that cell type looks
abnormal in the bone marrow. Very few or no blasts
are found in the bloodstream on at least 2 occasions
and less than 5 percent of cells in the bone marrow
are blast cells. Cells in the bone marrow have at least
one abnormal chromosome change that is linked with
MDS.
Atypical CML
(chronic myeloid leukemia), BCR-ABL1 negative
In this subtype, there is a high level of white blood
cells in the bloodstream. More than 10 percent of
the cells are very young neutrophils. But, less than
20 percent of cells in the bloodstream are blast
cells. There is a higher-than-normal number of blood
cells in the bone marrow. Less than 20 percent of
cells in the bone marrow are blasts. This subtype
has cells that look similar to CML when viewed with
a microscope. But, the cells lack the chromosome
and gene changes found in typical CML. The key
changes in typical CML are the abnormal Philadelphia
chromosome and the BCR-ABL1 gene. This subtype
is not treated the same as typical CML.
Review
Blood cells are made in the soft tissue in the In MDS, the bone marrow makes abnormal
center of most bones called bone marrow. blood cells and doesnt make enough healthy,
mature blood cells for the body.
A blood stem cell is a cell from which all other
types of blood cells are made. MDS is divided into smaller groups based
on the features of the bone marrow and
MDS is a group of cancers that affect blood
blood cells. These smaller groups are called
cells in the bone marrow and bloodstream.
subtypes.
Medical history
Treatment planning starts with testing.
Your medical history includes any health events in
This section describes the tests that your life and any medicines youve taken. A medical
are used to check for and confirm history is needed for treatment planning. See Chart
2.1 for a full list of the tests that are recommended
(diagnose) MDS. These tests also
before treatment for MDS. Your doctor will ask about
help doctors plan treatment. This illnesses, injuries, and health problems that you have
information can help you use the had. This includes the timing and severity of any low
blood cell counts (cytopenias). Your doctor will also
Treatment guide in Part 5. It may also ask about prior infections, abnormal bleeding, and the
help you know what to expect during number of blood transfusions youve had.
testing.
Your doctor will also ask about any symptoms youve
had that may be due to MDS. This information may
affect which cancer treatment is best for you. It may
help to make a list of old and new medicines while at
home to bring to your doctors office.
Physical exam
Doctors usually perform a physical exam along with
taking a medical history. A physical exam is a review
of your body for signs of disease such as infection
and areas of unusual bleeding or bruising.
CBC (complete blood count) with differential HIV (human immunodeficiency virus) testing
Iron, ferritin, folate, and vitamin B12 FISH (fluorescence in situ hybridization)
Cytogenetic testing
Other tests to assess the cause of Track your health information and
low blood cell counts
blood test results in one place. This
A number of health conditions can also cause a low
number of red blood cells and other problems similar can help you understand how your
to MDS. To confirm MDS, more blood tests will be MDS is progressing and how treatment
done to rule out other health conditions. The main is working. Being able to put your
tests that may be used to learn more about the cause
of low blood cell counts are described next.
hands on your health records quickly
is a critical part of being a strong self-
Serum EPO advocate.
EPO (erythropoietin) is a substance that tells
(stimulates) the bone marrow to make more red - Patient Advocate
blood cells. The body normally makes more EPO in AAMDS International Foundation
response to low levels of oxygen, which is carried
in red blood cells. Measuring the amount of EPO in Assess for thyroid problems
the blood can help find out the cause of anemia. The The thyroid makes hormones that help control how
amount of EPO in the blood is called serum EPO. The fast the body uses energy. The hormones also affect
serum EPO level is measured in mU/mL (milliunits other body functions. An underactive thyroidwhen it
per milliliter). isnt making enough hormonescan lead to anemia.
Thus, a test of the amount of TSH (thyroid-stimulating
A low level of EPO can cause anemia and may be a hormone) in the blood may be used to check how well
sign of a health problem other than MDS. A low level the thyroid is working. A high level of TSH in the blood
of EPO can also make anemia worse in a person with can be a sign that the thyroid isnt making enough
MDS. Most patients with MDS-related anemia have hormones.
relatively low serum EPO levels.
Copper level
Iron, ferritin, folate, and vitamin B12 Copper is a mineral that helps with many processes
Iron is a mineral that the body needs to make red in the body. A low level of copper can cause the
blood cells. Iron is an important part of hemoglobin number of red blood cells and white blood cells to be
the protein in red blood cells that carries oxygen. low. It can also cause blood cells to have an abnormal
Ferritin is a protein that binds to iron and stores it for size, shape, or look. Assessing the level of copper in
use in the body. The amount of ferritin in the blood the blood is not a standard test for MDS. But, it may
reflects the amount of iron stored in the body. be done in certain cases to rule out other causes of
the abnormal appearance or number of blood cells.
Folate and vitamin B12 are other nutrients in the body
that are needed to make red blood cells. A shortage HIV testing
of any one of these substances can cause anemia. A HIV (human immunodeficiency virus) can cause
shortage of folate or vitamin B12 can also cause red low blood cell counts. It can also cause blood cells
blood cells to have an abnormal shape, size, or look. to have an abnormal size, shape, or look. In certain
cases, tests may be done to rule out HIV as the
cause of these symptoms.
An increased number of young cells or very The number of blast cells in the bone marrow is
young cells (blast cells), important. In a healthy person, less than 5 percent
More than the normal number of cells in the of cells in the bone marrow are blast cells. This
bone marrowcalled hypercellular bone means that less than 5 out of every 100 bone marrow
marrow, cells are blast cells. In a person with MDS, up to 19
Less than the normal number of cells in the percent of cells in the bone marrow may be blast
bone marrowcalled hypocellular bone cells. In some cases, MDS can progress to a more
marrow, and aggressive (fast-growing) cancer called AML. In AML,
Red blood cells that have too much or too little more than 19 percent of cells in the bone marrow are
iron. blast cells.
A key feature of MDS is that it causes dysplasia in one But, the cell assessment and iron stain are not the
or more types of blood cells. In some types of MDS, only tests that will be done on the bone marrow
red blood cells have too much iron. To check for this, samples. Tests of genes and chromosomes will also
a special dye called an iron stain is placed on the be done. These are called genetic tests and they are
sample of liquid bone marrow. The excess iron shows described in the next section.
up as small dots in a circle (ring) around the center of
the cells. Thus, these cells are called ring sideroblasts.
Figure 2.1
Bone marrow biopsy
Doctors use a bone marrow biopsy and aspiration to remove a sample of bone marrow for testing.
These tests are often done at the same time on the hip bone.
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
Genetic tests
Cytogenetic testing
Cytogenetic testing uses a microscope to examine
the chromosomes inside of cells. This type of test is
used to look for abnormal changes (defects) in the
chromosomes. It is often done on a sample of bone
marrow. It can also be done on a sample of blood.
Review
A medical history, physical exam, and blood Genetic tests check for abnormal changes in
tests can reveal signs of cancer. the genes and chromosomes of MDS cells.
They can be used to assess prognosis and
Different types of blood tests are done to
guide treatment choices.
assess the extent and cause of low blood cell
counts. Blood tests are also used to see if you
have an illness other than cancer.
IPSS IPSS-R
The IPSS was the first prognostic scoring system The IPSS-R was developed in 2012. It is an updated
for MDS to be broadly used. It was created almost (revised) version of the original IPSS. A key way the
20 years ago. Currently, it is still the most commonly IPSS-R differs is that it scores the types and severity
used scoring system. of low blood cell counts. It also scores a wider range of
chromosome changes. And, it classifies MDS into five
The IPSS scores three main factors to classify MDS risk groups instead of four. As a result, the IPSS-R is
into four risk groups. See Chart 3.1. The scores for all better at predicting prognosis than the IPSS.
of the factors are added together to make the overall
risk score. This is called the IPSS score and it is used This system gives points for five main prognostic
to assign the IPSS risk group. factors. See Chart 3.1. The points for each of the
factors are added together to make the IPSS-R score
and assign the IPSS-R risk group.
System Prognostic factors that are scored Risk groups based on total risk score
Percent of blasts in the bone marrow Very Low IPSS-R Risk Score = 1.5 or lower
Score of 0, 1, 2, or 3 points
Chromosome changes Low IPSS-R Risk Score = 2 to 3
Score of 0, 1, 2, 3, or 4 points
Hemoglobin level
IPSS-R Intermediate IPSS-R Risk Score = 3.5 to 4.5
Score of 0, 1, or 1.5 points
Platelet count
High IPSS-R Risk Score = 5 to 6
Score of 0, 0.5, or 1 point
Neutrophil count
Score of 0 or 0.5 points Very High IPSS-R Risk Score = 6.5 or higher
When planning treatment, doctors often look at Risk groups also give doctors a general idea of how
the risk groups in terms of lower-risk and higher- long a group of patients might live with MDS without
risk MDS. Lower-risk MDS includes certain risk treatment. This does not apply to patients who
groups from each of the scoring systems. Likewise, receive treatment for MDS. It also does not predict
higher-risk MDS includes risk groups from each of how long a specific patient might live. Some patients
the scoring systems. Chart 3.2 shows how the risk will live many more years and others will live fewer
groups are split into these two main categories. years. If you want to learn more, talk to your doctor or
nurse. They will be able to give you information that is
In general, lower-risk MDS is more likely to grow and specific to you.
progress slowly over time. It may not cause many or
severe symptoms for a long time. Thus, less intensive
treatment is often used.
Review
A prognosis is a prediction of the pattern and MDS is classified into risk groups based on
outcome of disease. the risk score. Doctors use risk groups to
decide what type of treatment is needed and
Something that affects and helps predict
when.
the likely outcome of a disease is called a
prognostic factor. When planning treatment, doctors look at the
risk groups in terms of lower-risk MDS and
Doctors use prognostic scoring systems
higher-risk MDS.
to rate the severity of MDS to help plan
treatment.
Supportive care
Part 4 describes the main types of
Supportive care is treatment given to relieve the
treatment for MDS. Knowing what a symptoms caused by cancer and side effects of
treatment is will help you understand cancer treatment. It doesnt treat the cancer itself.
The goal of supportive care is to improve quality of life
your treatment options listed in the
and relieve any discomfort you may have.
Treatment guide in Part 5. There is
more than one treatment for MDS. Supportive care is an important part of the overall
treatment for MDS. It can address many needs. One
Not every person will receive every example is treatment for physical and emotional
treatment listed in this chapter. symptoms. It can also help with treatment decisions
and coordination between health care providers.
Cancer and its treatments can cause Feelings of anxiety and depression are
bothersome symptoms. The stress of having common among people with cancer. At your
cancer can also cause symptoms. There are cancer center, health care providers such as
ways to treat many symptoms, so tell your doctors, nurses, cancer navigators, social
treatment team about any that you have. workers, and other experts can help. Help
can include support groups, talk therapy,
or medication. Some people also feel better
You may lose sleep before, during, and after by exercising, talking with loved ones, or
treatment. Getting less sleep can affect your relaxing.
mood, conversations, and ability to do daily
tasks. If possible, allow yourself to rest, let
people do things for you, and talk with your You may be unemployed or miss work
doctor about sleep medication. Behavioral during treatment. Or, you may have too
sleep medicinea type of talk therapymay little or no health insurance. Talk to your
also help. treatment team about work, insurance,
or money problems. They will include
information in the treatment plan to help you
manage your finances and medical costs.
There are a number of high-intensity drugs for AML few. Some side effects can be very serious while
that could also be used for certain patients with MDS. others can be unpleasant but not serious. Most side
These drugs work in different ways to kill unhealthy effects appear soon after treatment starts and will go
cells in your blood and bone marrow. They tend to away after treatment ends. But, other side effects are
work well against fast-growing cells. But, they are long-term and may appear years later.
very toxic and kill normal cells along with cancer cells.
Thus, these drugs are often only used for MDS that is The side effects of chemotherapy depend on many
more likely to progress to AML. The goal is to kill all of factors. This includes the drug, the dose, and the
the abnormal cells in your body to stop the MDS from person. In general, side effects are caused by the
turning into AML. death of fast-growing cells, which are found in the
intestines, mouth, and blood. Thus, common side
Most of the high-intensity drugs are given as IV effects of chemotherapy are nausea, vomiting,
infusions. If you will have high-intensity chemo, ask diarrhea, not feeling hungry, hair loss, and low blood
your doctor how many cycles are needed and how cell counts.
many days of treatment are in each cycle.
Not all side effects of chemotherapy are listed here.
Side effects of chemotherapy Be sure to ask your treatment team for a complete
A side effect is an unhealthy or unpleasant physical list of common and rare side effects. If a side effect
or emotional condition caused by treatment. Each bothers you, tell your treatment team. There may be
treatment for MDS can cause side effects. The ways to help you feel better. There are also ways to
reactions to chemotherapy differ between people. prevent some side effects.
Some people have many side effects. Others have
The transplanted blood stem cells then travel to your Donor lymphocyte infusion
bone marrow and grow. They will make new, healthy
blood cells. This is called engraftment. It usually takes DLI (donor lymphocyte infusion) is a treatment in
about 2 to 4 weeks. which the patient receives lymphocytes from the
same person who donated blood stem cells for the
Until then you will have little or no immune defense. HCT. A lymphocyte is a type of white blood cell that
This puts you at high risk for infection and bleeding. helps the body fight infections. The purpose of a DLI
You will likely need to stay in a hospital in a very is to stimulate an immune response called the GVL
clean room for some time. It may take a few weeks effect. This treatment may be used for MDS that
or months for blood cells to fully recover so that your came back or progressed after an HCT.
immune system is back to normal.
Possible side effects of a DLI are similar to those
Side effects of allogeneic HCT caused by an allogeneic HCT. Because this treatment
A side effect is an unhealthy or unpleasant physical starts an immune response in your body, you are
or emotional condition caused by treatment. Common at risk for GVHD. Some other side effects of a DLI
side effects of chemotherapy, which is given before are weakened (suppressed) bone marrow and an
the transplant, are described on page 37. You will increased risk of infection.
likely feel tired and weak shortly after the transplant
while waiting for the new blood stem cells to grow in
the bone marrow.
It is important to tell your treatment team if you are using any CAMs.
They can tell you which CAMs may be helpful and which CAMs may
limit how well treatments work.
Clinical trials
New tests and treatments arent offered to the public
as soon as theyre made. They need to be studied
first. New uses of tests and treatments also need to
be studied. A clinical trial is a type of research that
studies a test or treatment.
Tests and treatments go through a series of clinical Joining a clinical trial has benefits. First, youll have
trials to make sure theyre safe and work. Without access to the most current cancer care. Second, you
clinical trials, theres no way to know if a test or will receive the best management of care. Third, the
treatment is safe or helpful. Clinical trials are done in results of your treatmentboth good and badwill be
a series of steps, called phases. The four phases of carefully tracked. Fourth, you may help other patients
clinical trials are described next using the example of with cancer.
a new drug treatment:
Clinical trials have risks, too. Like any test or
Phase I trials aim to find the best dose and way to treatment, there may be side effects. Also, new tests
give a new drug with the fewest side effects. If a drug or treatments may not help. Another downside may
is found to be safe, it will be studied in a phase II trial. be that paperwork or more trips to the hospital may
be needed.
Phase II trials assess if a drug works for a specific
type of cancer. They are done in larger groups of To join a clinical trial, you must meet the conditions
patients with the same type of cancer. of the study. Patients in a clinical trial often have
a similar cancer type and general health. This is
Phase III trials compare a new drug to the standard to know that any improvement is because of the
treatment or to a placeboa substance with no treatment and not because of differences between
effects. These are randomized, meaning patients are patients. You also must review and sign a paper
put in a treatment group by chance. Phase III trials called an informed consent form to join a clinical trial.
are done to learn about short- and long-term side This form describes the study in detail, including the
effects and about safety. risks and benefits.
Phase IV trials test new drugs approved by the FDA Ask your treatment team if there is an open clinical
(U.S. Food and Drug Administration) to learn more trial that you can join. There may be clinical trials
about short-term side effects, long-term side effects, where youre getting treatment or at other treatment
and safety. They involve many patients with different centers nearby.
types of cancer.
My notes
Review
Supportive care is treatment for the symptoms An HCT replaces damaged or diseased cells
or health conditions caused by cancer or in the bone marrow with healthy blood stem
cancer treatment. Supportive care is an cells.
important part of treatment for MDS.
Clinical trials give people access to new tests
Immunotherapy is treatment with drugs that and treatments that arent usually received.
modify the immune system to help the body
fight cancer.
Treatment options
Part 5 is a guide through the There are multiple treatment options for MDS.
Treatment options that are best for you depend on a
treatment options for people with number of factors. This includes the features of the
MDS. This information is taken from cancer, such as the MDS subtype and risk score, as
well as your age and health status.
the treatment guidelines written
by NCCN experts of MDS. These The treatment options in Part 5 are organized by
treatment guidelines list options for MDS risk groups and symptoms. The timing, intensity,
and goal of treatment differs depending on the risk
people with MDS in general. Thus, group. To plan treatment, doctors put risk groups into
your doctors may suggest other two categories: lower-risk MDS and higher-risk MDS.
treatment for you based on your
Lower-risk MDS includes the following risk
health and personal wishes. Fully groups: IPSS Low and Intermediate-1; IPSS-R Very
discuss your treatment options with Low, Low, and Intermediate; and WPSS Very Low,
Low, and Intermediate.
your doctor.
Higher-risk MDS includes the following risk
groups: IPSS Intermediate-2 and High; IPSS-R
Much effort has been made to make this guide easy Intermediate, High, and Very High; and WPSS High
to read. Charts list the treatment options and map the and Very High.
steps through the treatment process. The text along
with each chart explains the information shown in the Lower-risk MDS is more likely to grow slowly and
chart. may not progress to AML for a long time. Thus,
low-intensity treatments are used first. The goal of
treatment for lower-risk MDS is to improve blood cell
counts, lessen the need for blood transfusions, and
improve quality of life.
Clinical trial
Chart 5.1.1 shows the treatment options for patients effects. These tests are also used to check how well
with lower-risk MDS and anemia that is causing treatment is working. An outcome or improvement
symptoms. The options differ based on the types of caused by treatment is called a treatment response.
chromosome changes in the MDS cells and the level
of EPO in your blood. One key chromosome change The goal is to increase red blood cell counts and
is when MDS cells are missing part of chromosome 5. lessen the need for red blood cell transfusions.
This change is called del(5q). The amount of natural Doctors often assess the response about 2 to 4
EPO in your blood is called the serum EPO level. months after the start of treatment with lenalidomide.
If tests do not show a treatment response, then your
next options are the same as those listed for MDS
Treatment options for MDS with del(5q) without del(5q).
If MDS cells have the del(5q) chromosome If tests show a response, you should continue this
change, treatment with lenalidomide is treatment until it stops working or side effects get too
recommended. But, this drug should not be given severe. Over time, your doctor may lower the dose of
if you have a very low number of neutrophils or lenalidomide to lessen the side effects. (See page 38
platelets. Your doctors will give tests during treatment for more details about lenalidomide.)
to check your blood cell counts and watch for side
Treatment options for MDS without The second option is to receive lenalidomide. This
del(5q) drug works best against MDS with the del(5q)
chromosome change (described above). But, it may
If tests show serum EPO 500 mU/mL, treatment also be helpful for some other patients. The third
with blood cell growth factors is recommended. The option is to receive treatment within a clinical trial.
two main options are epoetin alfa and darbepoetin (See Part 4 for more details about each treatment.)
alfa. These drugs are red blood cell growth factors
also called ESAs. ESAs act like EPO and stimulate Your doctor will give tests during treatment to check
the body to make more red blood cells. Thus, they if it is working well to improve blood cell counts
work best when there is a lower level of natural EPO and other signs of MDS. How long it takes to see a
in the blood. treatment response depends on which treatment you
have. If tests show a response, treatment may be
ESAs may be given alone or along with G-CSF. continued until it stops working. But, treatment may
G-CSF is a white blood cell growth factor. Studies need to be stopped early if side effects become too
show that adding G-CSF can improve how well ESAs severe. This is called treatment intolerance.
work for some patients. See Next steps at the end of
this section.
Chart 5.1.2 Next treatment options for lower-risk MDS with anemia
Azacitidine or decitabine,
Clinical trial
Azacitidine,
Clinical trial, or
Decitabine,
Lenalidomide, or
Consider allogeneic HCT for certain patients
Clinical trial
Chart 5.1.2 shows the next options for if prior After treatment with epoetin alfa or darbepoetin
treatment didnt work, stopped working, or had very alfa, your doctor may consider IST next. Your doctor
bad side effects. There are several options to choose will look at the features of the MDS cells and other
from. Which option is best for you depends on the factors to decide if this treatment might work well
treatment you had before. for you. (See page 38 for details.) If there is a good
chance that MDS will respond to IST, then you will
Your doctor will give tests during treatment to check receive ATG with or without cyclosporine. If MDS is not
how well its working. If tests show a treatment likely to respond to IST, then the next options are the
response, you will stay on that treatment as long same as those listed for after treatment with ATG or
as it is working well. It will be stopped once it is no cyclosporine.
longer working well. Or, it may be stopped early if side
effects get very bad. After treatment with ATG or cyclosporine, there
are three main options to choose from next. The
If one treatment doesnt work or has to be stopped, a first option is to receive low-intensity chemotherapy
different option will be tried. Each time this happens, with azacitidine or decitabine. The second option is
refer to the chart for the next options. These options to receive lenalidomide, unless you have a very low
are also described next. number of platelets or neutrophils. The third option is
to join a clinical trial.
Chart 5.2 shows the treatment options for patients If there is a good chance that MDS will respond
with lower-risk MDS but without anemia. Instead, the to IST, then you will receive ATG with or without
number of platelets or white blood cells is low. Or, the cyclosporine. The third option is to receive treatment
number of blast cells in the bone marrow is high. within a clinical trial.
There are three main treatment options to choose Your doctor will give tests during treatment to check
from. The first option is to receive azacitidine or if it is working well to improve blood cell counts
decitabine. Both are low-intensity chemotherapy and other signs of MDS. This is called a treatment
drugs. They are also a lot alike in how they work response. How long it takes to see a treatment
against MDS. They can help to increase blood cell response depends on which treatment you have.
counts and lessen the need for transfusions. They Sometimes MDS grows or gets worse during
can also help to slow MDS growth and progression treatment. This is called progression. The next
to AML. With either drug, at least 4 to 6 cycles of treatment options depend on how well initial treatment
treatment should be given to decide if it is working. worked.
Treatment with IST may also be an option for some If tests show a response, then you will stay on the
patients. Your doctor will look at the features of the same treatment as long as it keeps working. Once the
MDS cells and other factors to decide if this treatment MDS grows or gets worse, the next treatment options
might work well for you. (See page 38 for details.) will be tried.
Allogeneic HCT,
Allogeneic HCT is a good option for you, and
Azacitidine or decitabine followed by allogeneic HCT, or
A well-matched donor is available
High-intensity chemo followed by allogeneic HCT
Azacitidine (preferred),
Allogeneic HCT may be a good option for you,
Decitabine, or
but A well-matched donor is not available
Clinical trial
Azacitidine (preferred),
Allogeneic HCT is not a good option for you, or
Decitabine, or
A well-matched donor is not available
Clinical trial
Chart 5.3.1 shows the treatment options for Your doctor will look at many factors to decide if high-
higher-risk MDS. To help decide which option is intensity treatment is a good option for you. Such
best for you, your doctor will first assess if you are factors include your personal preference, your age,
able to have high-intensity treatment. High-intensity how well you can do daily activities, and other health
treatment includes allogeneic HCT and high-intensity conditions. Another key factor is if there is a well-
chemotherapy. matched donor for the allogeneic HCT.
High-intensity treatments aim to slow or stop MDS If an allogeneic HCT is a good option for you
progression to AML and improve survival. But, they and a donor has been found, there are three main
can also cause very bad side effects. Side effects are options to choose from. The first option is to receive
often more severe for patients who are older or have an allogeneic HCT right away. High-dose conditioning
other health problems. Not all patients can tolerate or reduced-intensity conditioning may be used
the severe side effects. for the HCT. (See page 39 for more details about
conditioning treatment.)
The second option is to receive azacitidine or The second option is to receive decitabine, which is
decitabine first and then an allogeneic HCT. This may also a low-intensity chemotherapy drug. It is a lot like
be used to lower the number of blast cells in your azacitidine in how it works against MDS. Decitabine
bone marrow before the HCT. It may also be a good can lower the chance that MDS will progress to
option if you are still waiting for a well-matched donor. AML in some patients. The third option is to receive
treatment within a clinical trial.
The third option is to receive high-intensity
chemotherapy first and then an allogeneic HCT. High-
intensity chemo as part of a clinical trial is preferred.
The high-intensity chemo can help to lower the
number of blast cells in your bone marrow before the
HCT. But, it can cause very severe side effects and
may not be a good choice for all patients. Next steps:
If an allogeneic HCT is not a good option for
you or a donor hasnt been found, there are three See Chart 5.3.2 on page 56 for the
options to choose from. The first option is to receive
next options after initial treatment for
azacitidine, a low-intensity chemotherapy drug.
This is the preferred option for patients with higher- higher-risk MDS.
risk MDS who are not able to have high-intensity
treatment. Azacitidine can lower the chance that MDS
will progress to AML in some patients. It can also help
some patients have improved blood cell counts and
live longer than they would without treatment. Your
doctor may refer to this as improved survival.
Clinical trial, or
Continue treatment until
Response
it stops working
Supportive care
Azacitidine or
decitabine
Clinical trial, or
Relapse or
no response
Supportive care
Clinical trial, or
Relapse or
Clinical trial
no response
Supportive care
Chart 5.3.2 shows the next options used after initial If you had an allogeneic HCT, and tests show a
treatment for higher-risk MDS. There are several relapse or no response, there are three main options
options to choose from. Which option is best for you to choose from. The first option is to have a second
depends on which treatment you had before and how allogeneic HCT or a DLI. This may be a good option if
well it worked. the response to the first HCT lasted for a while before
tests showed a relapse.
Your doctor will give tests during treatment to check
how well its working. An outcome or improvement The second option is to receive azacitidine or
caused by treatment is called a treatment response. decitabine. Both are low-intensity chemotherapy
How long it takes to see a treatment response drugs. They are a lot alike in how they work against
depends on the type of treatment used. A relapse is MDS. With either drug, treatment should be continued
the return or worsening of MDS after a response or as long as it is working well. The third option is to join
period of improvement. a clinical trial.
Assessing anemia
Supportive care
Chart 5.4.1 shows the initial steps to assess and time. You should also receive other supportive care
care for anemia. MDS is not the only health condition as needed. (For more details about supportive care,
that can cause anemia. A number of other factors can see page 32.)
cause or contribute to anemia. Thus, it is important
to check for any other health problems that might be
causing a low number of red blood cells. The tests
doctors use to assess anemia are described in Part 2
on page 16. Next steps:
Iron, folate, and vitamin B12 are nutrients in the body
that are needed to make red blood cells. A shortage See Chart 5.4.2 on page 60 for
of any one of these substances can cause anemia.
treatment options for MDS-related
Thus, your doctor will want to know if you have
the right amount of these nutrients. If any are low, anemia.
treatment with vitamin supplements may help.
My notes
Serum EPO
See options on Chart 5.1.1
>500 mU/mL
Chart 5.4.2 shows the treatment options for anemia to check your blood cell counts. These tests are
that is causing symptoms. The options differ based on also used to check how well treatment is working.
the features of the MDS cells and the level of EPO in An outcome or improvement caused by treatment is
your blood. The amount of natural EPO in your blood called a treatment response.
is called the serum EPO level.
The goal is to increase red blood cell counts and
One key feature is whether or not the MDS cells are lessen the need for red blood cell transfusions.
missing part of chromosome 5. This chromosome Doctors often assess the response about 2 to 4
change is called del(5q). Another key feature is the months after the start of treatment with lenalidomide.
amount of ring sideroblasts found in the bone marrow. If tests show a response, you should continue this
treatment until it stops working or side effects get too
If MDS cells have the del(5q) chromosome severe. Over time, your doctor may lower the dose of
change, treatment with lenalidomide is lenalidomide to lessen the side effects. (See page 38
recommended. But, this drug should not be given for more details about lenalidomide.)
if you have a very low number of neutrophils or
platelets. Your doctors will give tests during treatment
For patients with serum EPO 500 mU/ For patients with serum EPO >500 mU/mL,
mL, treatment with blood cell growth factors is treatment with red blood cell growth factors is not
recommended. The two main options are epoetin alfa recommended. EPO is made naturally in your body to
and darbepoetin alfa. Both drugs are red blood cell stimulate your bone marrow to make more red blood
growth factorsalso called ESAs. ESAs are drugs cells. Red blood cell growth factors are drugs that
that act like EPO, a substance that is made naturally act like EPO. These drugs dont work as well when
in your body to stimulate the growth of new red blood there is a higher level of natural EPO in the blood.
cells. Thus, these drugs work best when there is a Therefore, other types of treatments should be used.
lower level of natural EPO in the blood. See Next steps at the end of this section.
My notes
3. What is the cancer risk score and risk group? Does this risk score or group mean the cancer has
progressed a lot?
5. What are the chances that this type of MDS will become AML?
8. Would you give me a copy of the pathology report and other test results?
9. Can the cancer be cured? If not, how well can treatment stop the cancer from growing?
4. Are you suggesting options other than what NCCN recommends? If yes, why?
9. What are the benefits of each option? Does any option offer a cure? Are my chances any better
for one option than another? Less time-consuming? Less expensive?
10. What are the risks of each option? What are possible complications? What are the rare and
common side effects? Short-lived and long-lasting side effects? Serious or mild side effects?
Other risks?
11. What can be done to prevent or relieve the side effects of treatment?
1. Will I have to go to the hospital or elsewhere? How often? How long is each visit?
2. Do I have a choice of when to begin treatment? Can I choose the days and times of treatment?
3. How do I prepare for treatment? Do I have to stop taking any of my medicines? Are there foods I
will have to avoid?
6. How much will the treatment cost me? What does my insurance cover?
3. How many procedures like the one youre suggesting have you done?
If the two opinions are the same, you may feel more
at peace about the treatment you accept to have.
If the two opinions differ, think about getting a 3rd
opinion. A 3rd opinion may help you decide between
My notes
Aplastic Anemia and MDS International Aplastic Anemia and MDS International
Foundation Foundation
www.aamds.org/about/MDS www.aamds.org/support
Dictionary
Acronyms
Dictionary
acute myeloid leukemia (AML) bone marrow aspiration
A fast-growing cancer that starts in the bone marrow and The removal of a small amount of liquid bone marrow to test
causes too many immature white blood cells to be made. for disease.
bloodstream cytopenia
Blood that flows throughout the body in small tubes called A condition in which the number of blood cells is low.
blood vessels.
del(5q)
bone marrow An abnormal chromosome change in which the q part of
The soft, sponge-like tissue in the center of most bones chromosome 5 is missing (deleted).
where blood cells are made.
higher-risk MDS
MDS that is more likely to progress faster or turn into acute
myeloid leukemia quickly if not treated.
immunomodulators lymphocyte
A type of white blood cell that helps protect the body from
Drugs that change (modify) different parts of the immune
infection and disease.
system.
transfusion
A slow injection of whole blood or parts of blood into a vein.
Acronyms
AML HCT WPSS
acute myeloid leukemia hematopoietic cell transplant WHO classification-based Prognostic
Scoring System
ATG HIV
antithymocyte globulin human immunodeficiency virus
CBC HLA
NCCN Abbreviations and
complete blood count human leukocyte antigen Acronyms
CML IPSS NCCN
chronic myeloid leukemia International Prognostic Scoring National Comprehensive Cancer
System Network
CMML
chronic myelomonocytic leukemia IPSS-R NCCN Patient Guidelines
Revised International Prognostic NCCN Guidelines for Patients
DLI Scoring System
donor lymphocyte infusion
NCCN Guidelines
IST
DNA NCCN Clinical Practice Guidelines in
immunosuppressive therapy
deoxyribonucleic acid Oncology
IV
EPO intravenous
erythropoietin
MDS
ESA myelodysplastic syndromes
erythropoietin-stimulating agent
MDS/MPN
FAB myelodysplastic/myeloproliferative
French-American-British
neoplasms
FDA mU/mL
U.S. Food and Drug Administration
milliunits per milliliter
FISH RAEB
fluorescence in situ hybridization
refractory anemia with excess blasts
G-CSF RARS
granulocyte colony-stimulating factor
refractory anemia with ring sideroblasts
GM-CSF RCMD
granulocyte-macrophage granulocyte
refractory cytopenia with multilineage
colony-stimulating factor
dysplasia
GVHD RCUD
graft-versus-host disease
refractory cytopenia with unilineage
GVL dysplasia
graft-versus-leukemia
WHO
World Health Organization
Acute Lymphoblastic Leukemia Malignant Pleural Mesothelioma Non-Small Cell Lung Cancer
Caring for Adolescents and Melanoma Ovarian Cancer
Young Adults (AYA)* Multiple Myeloma Pancreatic Cancer
Chronic Lymphocytic Leukemia Myelodysplastic Syndromes Prostate Cancer
Chronic Myelogenous Leukemia Non-Hodgkins Lymphomas Soft Tissue Sarcoma
Colon Cancer Diffuse Large B-cell Lymphoma Stage 0 Breast Cancer
Esophageal Cancer Follicular Lymphoma
Stages I and II Breast Cancer
Mantle Cell Lymphoma
Hodgkin Lymphoma Stage III Breast Cancer
Mycosis Fungoides
Kidney Cancer Peripheral T-cell Lymphoma Stage IV Breast Cancer
Lung Cancer Screening
* Print copies unavailable at this time. Check NCCN.org/patients for updates. As of May 12, 2016
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Index
acute myeloid leukemia (AML) 9, 11, 21, 27, 2930,
3637, 47, 49, 52, 5455, 66
anemia 13, 1819, 2829, 3234, 46, 4853, 58, 6061
blood cell growth factor 3334, 49, 61
blood stem cell 78, 14, 3940, 44
bone marrow 4, 712, 14, 1722, 24, 2728, 3334,
3640, 44, 46, 49, 52, 55, 6061
chemotherapy 3637, 3940, 44
chromosome 8, 1012, 2122, 24, 2728, 38, 48, 6067
clinical trial 42, 44, 4857, 67
cytopenia 10, 13, 16, 18, 27
dysplasia 8, 10, 12, 18, 2021
gene 8, 12, 2124, 36
hematopoietic cell transplant (HCT) 20, 3940, 44, 5056
higher-risk MDS 2930, 4647, 5457
high-intensity chemo 3637, 5455
immunosuppressive therapy (IST) 3738, 4852
lower-risk MDS 2930, 38, 4653
low-intensity chemo 36, 4950, 52, 5556
prognosis 2224, 2628, 30, 66
prognostic scoring 2630
risk group 2730, 39, 47, 66
risk score 2630, 47, 66
serum EPO 17, 19, 34, 4849, 6061
side effect 32, 3640, 42, 4850, 5455, 60, 67
subtype 1012, 14, 23, 2729, 47
supportive care 3235, 44, 5658
transfusion 16, 20, 3334, 3839, 4749, 52, 58, 6061
Myelodysplastic
Syndromes
Version 1.2016
NCCN Foundation gratefully acknowledges our advocacy supporter, Aplastic Anemia and MDS International Foundation, and our
industry supporter Amgen, Inc. for their support in making available these NCCN Guidelines for Patients. NCCN independently
develops and distributes the NCCN Guidelines for Patients. Our industry supporters do not participate in the development of the NCCN
Guidelines for Patients and are not responsible for the content and recommendations contained therein.
PAT-N-0907-0616