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Acute
Lymphoblastic
Leukemia
Acute Lymphoblastic
Leukemia (ALL)
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 acute lymphoblastic leukemia. The
treatments in this book are also used for lymphoblastic lymphoma.
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 developing the NCCN Guidelines for Patients include:
Endorsed by
THE Leukemia & lymphoma society (LLS)
LLS is dedicated to developing better outcomes for blood cancer patients through research, education and patient
services and is happy to have this comprehensive resource available to patients with acute lymphoblastic leukemia.
www.LLS.org/informationspecialists
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.
Acute Lymphoblastic
Leukemia (ALL)
4 How to use this book 73 Part 6
Making treatment decisions
5 Part 1 Offers tips for choosing the best treatment
ALL basics for you.
Explains how and where this type of
cancer starts. 83 Glossary:
84 Dictionary
13 Part 2 90 Acronyms
Testing for ALL
Describes the tests used to confirm this 93 NCCN Panel Members
type of cancer and plan treatment.
94 NCCN Member Institutions
25 Part 3
Treatment planning 96 Index
Explains the main factors doctors use to
plan treatment thats right for you.
31 Part 4
Overview of cancer
treatments
Describes the types of treatments that are
used for ALL.
47 Part 5
Treatment guide
Presents treatment options based on your
health and age as well as the features of
the cancer.
Who should read this book? point out what applies to you and give you more
information. As you read through this book, you
Leukemia is a type of cancer that starts in may find it helpful to make a list of questions to
blood-forming cells in the bone marrow. Acute ask your doctors.
lymphoblastic leukemia is a fast-growing type of
leukemia that causes too many immature blood The recommendations in this book are based on
cells called lymphoblasts to be made in the bone science and the experience of NCCN experts.
marrow. Lymphoblastic lymphoma is similar, However, each patient is unique and these
but it causes too many lymphoblasts to build up recommendations may not be right for you. Your
in lymph nodes or other parts of the lymphatic doctors may suggest other tests or treatments
system. Patients and those who support them based on your health and other factors. If other
caregivers, family, and friendsmay find this suggestions are given, feel free to ask your
book helpful. It may help you discuss and decide treatment team questions.
with your doctors what care is best.
of most bones. See Figure 1.1. Blood cells are See Figure 1.2. Blast cells are new, very young
made from special blood-forming cells called blood (immature) blood cells that grow into adult (mature)
stem cells. Blood stem cells can become any type of blood cells over time. Different types of blast cells
mature blood cell. become different types of mature blood cells. Once
they are mature, the blood cells leave the bone
Blood stem cells go through a series of changes as marrow and enter the bloodstream.
they grow and develop to make new blood cells.
Figure 1.1
Blood cells in bone marrow
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
Figure 1.2
Blood stem cells make all types of
blood cells
What is ALL? Normal blood cells grow and then divide to make new
red blood cells, white blood cells, and platelets as the
Leukemias are cancers that start in blood-forming body needs them. When normal blood cells grow old
cells in the bone marrow. There is more than one type or get damaged, they die. New blood cells are then
of leukemia. Each type of leukemia is named based made to replace the old ones. In a person with ALL,
on how fast it grows and the type of blood cell in too many lymphoblasts are made.
which it begins.
Inside of all cells are coded instructions for building
This book focuses on ALL (acute lymphoblastic new cells and controlling how cells behave. These
leukemia). Acute means the leukemia grows and instructions are called genes. Genes are a part
progresses very fast. Lymphoblastic means it starts of DNA (deoxyribonucleic acid). DNA is grouped
in young white blood cells called lymphoblasts. together into long strands called chromosomes.
Lymphoblastic lymphoma is similar to ALL. The main See Figure 1.3. Changes (mutations) in genes
difference is that it starts in lymphoblasts within the cause normal lymphoblasts to become cancer cells.
lymphatic system. Researchers are still trying to learn what causes
genes to change and cause cancer.
Gene
Chromosomes
The abnormal lymphoblasts are called leukemia cells. Third, leukemia cells can spill out of the bone marrow
Leukemia cells differ from normal cells in a few key into the bloodstream. They can then spread to other
ways. First, leukemia cells grow more quickly and parts of the body. They may collect in the spleen,
live longer than normal cells. They divide and copy thymus, lymph nodes, liver, testicles, and the area
themselves to make more and more leukemia cells. around the brain and spinal cord.
See Figure 1.4. The leukemia cells quickly fill up the
bone marrow and crowd out healthy blood cells that
body needs.
Figure 1.4
Normal cell growth versus leukemia
cell growth
My notes
Review
White blood cells are part of your bodys Leukemia is a cancer that starts in blood-
disease-fighting system called the immune forming cells in the bone marrow.
system.
ALL is a fast-growing type of leukemia in
Most blood cells are made in the bone which too many young white blood cells called
marrowthe soft tissue in the center of most lymphoblasts are made. The lymphoblasts
bones. build up in the bone marrow and crowd out
healthy blood cells.
All types of blood cells are made from special
blood-forming cells called blood stem cells. Lymphoblastic lymphoma is similar to ALL.
The key way it differs is that it starts in
Blast cells are very young (immature) cells
lymphoblasts within the lymphatic system.
that become mature blood cells over time.
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. You will
are used to confirm (diagnose) ALL be asked about any illnesses, injuries, and health
problems youve had. Some health problems run in
and plan treatment. This information
families. Thus, your doctor may also ask about the
can help you use the Treatment guide health of your blood relatives.
in Part 5. It may also help you know
ALL may cause symptoms. Its important that your
what to expect during testing. Not doctor knows if you have them. Symptoms may
every person with acute lymphoblastic result from a shortage of blood cells. Or, they may
result from leukemia cells collecting in certain parts
leukemia will receive every test listed.
of the body. But, some patients may have few or no
symptoms of ALL.
Tests needed for all patients Tests that may be needed in some cases
Medical history and physical exam MRI (magnetic resonance imaging) of the head
CBC (complete blood count) with differential CT (computed tomography) of the head
Blood chemistry profile CT of the chest
TLS (tumor lysis syndrome) panel PET (positron emission tomography) of the chest
Blood clotting tests Echocardiogram
Lumbar puncture HLA (human leukocyte antigen) typing
diagnose ALL, but it can tell your doctor about your dangerous. It can cause serious damage to organs
overall health. This test is also repeated to check such as the kidneys and heart.
treatment results.
Blood clotting tests
Blood chemistry profile Blood clotting tests are used to assess if blood is able
A blood chemistry profile measures the levels of to clot (coagulate) the way it should. Platelets and
different chemicals in your blood. Chemicals in your proteins called clotting factors help control bleeding in
blood come from you liver, bone, and other organs the body.
and tissues. Abnormal levels of certain chemicals in
the blood may be a sign that an organ isnt working When a person is cut or injured, platelets and clotting
well. Abnormal levels can be caused by cancer or factors clump together to form a clot to stop bleeding.
other health problems. Abnormal levels of platelets or clotting factors can
cause bleeding problems.
A blood chemistry profile is given along with other
initial tests for ALL. Doctors use this test to assess the HLA typing
general health of your body and organs. It can help HLAs (human leukocyte antigens) are special
check for organ damage caused by the leukemia cells proteins found on the surface of most cells in the
or ALL treatments. body. The unique set of HLA proteins on a persons
cells is called the HLA type or tissue type. All cells
Liver function tests in a single person have the same HLA type. This
The liver is an organ that removes waste from the helps the body to tell its own cells apart from foreign
blood and helps to digest food. Liver function tests cells. It also affects how the body responds to foreign
may be done along with a blood chemistry profile. substances.
This is to check the health of your liver.
HLA typing is a blood test that finds a persons
Liver function tests measure chemicals that are made HLA type. This test is used to find the right donor
or processed by the liver. Abnormal levelstoo low or for a stem cell transplanta treatment that may be
too highmay be a sign that your liver isnt working considered for some patients with ALL. (See Part 4 on
well. Abnormal levels may be caused by cancer, page 42 for details about this treatment). Your tissue
cancer treatments, or other health problems. type and the donors tissue type must be a near-
perfect match for this treatment to work.
Tumor lysis syndrome panel
TLS (tumor lysis syndrome) is a condition that Type and screen
occurs when many cancer cells die very quickly due Blood types differ among people just like tissue types
to treatment. As cancer cells die, they release their differ among people. Type and screen is test that
contents into the blood. This can cause very high finds a persons blood type. It also looks for signs that
levels of certain chemicals in the blood. certain blood types may not be a good match or may
not be safe to give to a patient. This test is needed if
A TLS panel measures the levels of these chemicals you will receive a transfusion of blood from another
in the blood. Uric acid is one of the chemicals person (donor). The donors blood type must be a
released by dying cancer cells. Very high levels of good match that works well with your blood type.
uric acid and other chemicals in the blood can be very
Bone marrow tests local anesthesia to numb the area of skin and
bone beneath. Once numb, a hollow needle will be
Bone marrow biopsy and aspiration inserted into your skin and then pushed into the bone
To confirm if you have ALL, a sample of tissue must to remove the liquid bone marrow with a syringe.
be removed from your body for testing. This tissue Then, a wider needle will be inserted into the bone
might be a blood sample, a biopsy of an enlarged to remove the solid bone and marrow sample. You
lymph node or organ, or a sample of bone marrow. may feel some pain while the samples are being
removed. Your skin may be bruised for a few days.
A bone marrow biopsy removes a small piece of solid The samples will be sent to a lab for testing.
bone along with a small amount of soft bone marrow
inside the bone. A bone marrow aspiration removes Cell assessment
a small amount of liquid bone marrow from inside the At the lab, a pathologist will look at the cells in a blood
bone. Often, both tests are done at the same time or bone marrow sample with a microscope. This
on the back of the hip bone. You will likely lie on your test is simply called cell assessment. Doctors may
side during this test. See Figure 2.1. also refer to this test as a morphologic assessment.
Special dyes may be used to stain the sample. This
You may be given a light sedative before the test. helps to show the differences between parts of a
Your doctor will then clean the area of skin where single cell and between many cells.
the biopsy will be done. Next, you will receive
Figure 2.1
Bone marrow biopsy
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
The pathologist will look at the size, shape, type, the number of leukemia cells present. This is helpful
and other features of the cells in the blood or bone for checking treatment results.
marrow sample. This is to see if the cells look more
like normal, mature cells or more like abnormal, Flow cytometry is sometimes used to measure the
immature cells. The number of very immature cells amount of DNA in the leukemia cells. In such cases,
blast cellsin the sample is important. a marker that reacts with DNA is used. The amount of
DNA reflects the number of chromosomes in the cells.
Normally, there are no blast cells in the blood. And, in This can help to show if the cells have too many or
a healthy person, blast cells make up no more than too few chromosomes.
5% of cells in the bone marrow. This means that no
more than 5 out of every 100 cells in the bone marrow
are blast cells. In a person with ALL, blast cells make
up 25% or more of cells in the bone marrow. This
means that at least 25 out of every 100 cells are blast
cells.
Flow cytometry
Flow cytometry is used to identify and count types
of cells in a sample. It can show if cells are normal
or abnormal. It can also tell the difference between
types of leukemia cells. This test is used to help
confirm ALL and find out the type of lymphocytes in
which it started. Flow cytometry is also used to check
treatment results.
Certain chromosome changes in the leukemia cells Sometimes parts of chromosomes break off and
can affect treatment options and outlook. Thus, this is switch with each other. This is called a translocation.
a key test that is used to help plan treatment for ALL. The Philadelphia chromosome is a key example of
This test is given along with other initial tests when a translocation that happens in some people with
ALL is first diagnosed. It may also be repeated to ALL. The Philadelphia chromosome is caused by a
check treatment results. translocation between parts of chromosomes 9 and
22. See Figure 2.2.
Fort this test, a pathologist will look at a map of the
chromosomes under a microscope. This map is called This translocation also forms the abnormal BCR-
a karyotype. It will show if there are any abnormal ABL fusion gene on the Philadelphia chromosome. A
changes in the size, shape, structure, or number of fusion gene is a new gene that is formed when parts
of two separate genes are joined (fused) together.
Figure 2.2
Philadelphia chromosome
The Philadelphia
chromosome is formed by a
translocation between parts
of chromosomes 9 and 22.
It contains the abnormal
BCR-ABL fusion gene.
This is a key chromosome
change that affects which
treatments are best for you.
FISH PCR/MRD
FISH (fluorescence in situ hybridization) is a very PCR (polymerase chain reaction) is a very sensitive
sensitive lab test that can detect certain abnormal test. Like FISH, it detects abnormal gene and
changes in a cells genes or chromosomes. It can chromosome changes (mutations) in cells. However,
detect most abnormal changes that can be seen with it can find mutations that are too small to be seen with
a microscope. It can also detect some changes that a microscope.
are too small to be seen with basic cytogenetic testing
(karyotyping). Doctors use this test to detect certain gene and
chromosome changes that are commonly found in
Doctors use FISH to detect certain abnormal gene ALL. An example of this is the BCR-ABL fusion gene.
and chromosome changes in leukemia cells. This This gene is found on the Philadelphia chromosome.
test uses special color dyes, called probes, that PCR can detect gene mutations and measure the
attach only to certain genes or parts of certain number of cells that have them.
chromosomes.
PCR is very helpful for checking how well treatment
For example, the Philadelphia chromosome is a is working. When the cells have certain genetic
common abnormal change found in adults with ALL. changes, PCR can find and measure the amount of
This chromosome contains the BCR-ABL fusion leukemia cells left. This test can find one leukemia
gene. To detect this, FISH uses color probes that cell among more than 10,000 normal cells. PCR
attach to the BCR gene and the ABL gene. The BCR- is the method used to find the amount of disease
ABL fusion gene is shown by the overlapping colors present after treatment. Doctors use this to assess
of the two probes. for MRD (minimal residual disease). The presence of
MRD is a key factor used to decide if more treatment
Like cytogenetic testing, FISH is used to help plan is needed. (See page 39 for more details about
and monitor treatment for ALL. This test can be checking treatment results.)
performed on a sample of blood or bone marrow.
PCR can be done on a sample of bone marrow or
blood. But, bone marrow is often preferred, especially
when checking treatment results.
Spinal fluid test During this test, you will be lying down or sitting on
an exam table as shown in Figure 2.3. If lying down,
ALL can spread to the fluid around your brain and your knees will be tucked up near your chest. If
spinal cord. This is called cerebrospinal fluid or spinal sitting, you will lean slightly forward and down over
fluid. To determine whether or not cancer is in spinal your knees.
fluid, a sample must be removed and tested.
Local anesthesia will be used to numb the lower part
A lumbar puncture is a procedure that is used to of your back over your spine. Next, a thin needle will
remove spinal fluid. It is also called a spinal tap. be inserted between the bones of your spine and
A lumbar puncture is often done when ALL is first into the space around your spinal cord. The needle
diagnosed. But, it may be done at a later time that fits will be used to take a sample of spinal fluid. You may
with your treatment plan. A lumbar puncture can also feel some pressure during the procedure. The fluid
be used to inject cancer drugs into the spinal fluid. sample will then be sent to a lab for testing for the
presence of leukemia cells.
Figure 2.3
Lumbar puncture
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
Imaging tests PET is not a standard test for ALL and it is not needed
for all patients. But, a PET scan of your chest is
Imaging tests take pictures of the inside of your body. recommended if other tests showed a mass in your
Imaging tests are not often used for ALL. However, chest. It may be done again after treatment to check if
they may be useful to look for infections or to check for the mass in your chest is gone.
signs that ALL has spread to the brain and spinal cord.
Echocardiogram
Imaging tests are often easy to undergo. Before the An echocardiogram is an imaging test of your heart. It
test, you may be asked to stop eating or drinking for uses sound waves to make pictures. This test is used
several hours. You also should remove any metal to check how well your heart is working. It shows your
objects that are on your body. For some imaging doctor how your heart is beating and pumping blood.
tests, a contrast dye may be injected into your vein to
make the pictures clearer. Some treatments for ALL can damage your heart.
Thus, your doctor may want to test how well your
CT scan heart works to plan treatment. This is especially
CT (computed tomography) takes many pictures of important if youve had any heart problems in the
a body part from different angles using x-rays. See past. This test may be repeated during and after ALL
Figure 2.4. A computer combines all the pictures to treatment to check for any heart damage that may
make one clear picture. A CT scan of your head may have occurred.
be needed if you have symptoms that suggest ALL
might have spread to your brain and spinal cord. A CT
Figure 2.4 CT scan machine
scan of your chest may be needed for certain patients
to see if leukemia cells have collected in this area. A CT machine is large and has a tunnel in the
middle. During the test, you will lie on a table
that moves slowly through the tunnel.
MRI scan
MRI (magnetic resonance imaging) uses radio waves
and magnets to take pictures of the inside the body.
MRI scans create clear pictures of soft tissues and
bones. MRI scans are also very helpful for looking at
the brain and spinal cord. An MRI scan of your head
should be done if you have symptoms that suggest
ALL might have spread to your brain and spinal cord.
PET scan
PET (positron emission tomography) shows how your
cells are using a simple form of sugar. For a PET
scan, a sugar radiotracer will first be injected into your
body. The radiotracer is detected by a special camera
during the scan. Cancer cells look brighter than
normal cells because they use sugar more quickly.
Review
Cancer tests are used to plan treatment and Flow cytometry is used to identify the type of
check how well treatment is working. cells present in a sample based on the set
on proteins on the cell surface. This is called
Your medical history and the physical exam
immunophenotyping.
can reveal signs of disease.
Cytogenetic testing, PCR, and FISH help
Blood tests are used to look for signs of
doctors detect abnormal chromosome
cancer and check how well your organs are
changes in leukemia cells.
working.
Age issues in ALL results. The side effects of intensive treatments tend
to be more severe and harder to recover from for
A persons age at the time ALL is diagnosed is one older patients.
of the most important factors that doctors use to
plan treatment. As a result, recommendations in the Generally, doctors use the age of 65 as the cut-off for
Treatment guide are divided into two age groups: intensive treatments. This is because older patients
may not be able to tolerate them. But, age alone is
AYAs (adolescent and young adults) not a good gauge for deciding if a person can tolerate
patients who are 15 to 39 years of age, and these treatments.
Older adults patients who are 40 years of
age or older. A person older than 65 may be still in good health
overall and not have other serious health problems.
AYAs and older adults differ in many ways. These In this case, he or she may still benefit from more
differences carry over into personal, social, emotional, intensive treatments. Likewise, a person younger than
and medical needs. There are also key differences 65 may be in poorer health overall and have other
between AYAs and older adults with ALL that doctors serious health problems. In this case, he or she may
must consider when making treatment decisions. In not be able to tolerate intensive treatments.
particular, AYAs have much better outcomes when
given more intensive ALL treatments like those Thus, doctors must also consider your overall health
designed for children. as well as your age. Assessing your overall health,
fitness, and other current health problems is very
Intense treatments can cause serious side effects important. This includes checking how well organs
that get harder to tolerate with age. Because AYAs such as your heart, lungs, liver, and kidneys are
are usually able to tolerate the intensive treatments, working.
they benefit greatly and have much better treatment
What is a prognostic factor? Age: The leukemia cells in older patients tend to be
more resistant to treatment. Stronger treatments may
Several important factors affect treatment options be needed to kill all the leukemia cells and keep them
and the likely outcome (prognosis) of ALL. Something from coming back.
that affects and helps predict prognosis is called a
prognostic factor. Philadelphia chromosome: Leukemia cells that
have the Philadelphia chromosome can be harder to
Doctors use certain prognostic factors to help predict treat. But, new treatments have improved outcomes
how ALL will likely progress and respond to treatment. in the past few years.
This helps doctors plan how intensive treatment
needs to be for each patient to kill all the leukemia Chromosome changes: Certain changes in
cells and keep them from coming back. These factors chromosomes can make leukemia cells harder to
can also help doctors decide which type of treatment treat. This includes having fewer than the normal
will likely work best. number of chromosomes and having five or more
chromosome changes in the leukemia cells.
Some prognostic factors are linked with a lower
chance (risk) that ALL will come back after treatment. White blood cell count: The number of white
These are called good risk features. Other factors blood cells in the blood at the time ALL is diagnosed
are linked with a higher risk that ALL will come back can also affect prognosis. Having a very high white
after treatment. These are called poor risk features. blood cell count at diagnosis is a poor risk feature in
children and adolescents with ALL. This factor has a
Doctors give more intensive treatments for ALL that much smaller effect on treatment planning for adults
has poor risk features. But, the presence of poor risk with ALL.
features does not mean ALL cant be cured.
A number of factors can affect prognosis in ALL.
Some are more important for treatment planning
than others. The two main factors doctors use to plan
treatment are your age and the cytogenetic subtype.
But, other prognostic factors for ALL that may also be
helpful include:
Review
A number of factors help guide treatment ALL is classified into groups based on the
options and the likely outcome (prognosis). type of cellcalled the cell subtype. It is also
classified into smaller groups based on the
Something that affects and helps predict the
type of chromosome changes in the leukemia
likely outcome is called a prognostic factor.
cells. These are called cytogenetic subtypes.
Age is one of the most important factors that
affect treatment options.
Clinical trials are an important treatment option To join a clinical trial, you must meet the conditions
for people with ALL. Doctors are still studying of the study. Patients in a clinical trial often have a
what treatments work best for ALL. NCCN experts similar cancer type and general health. This is to
recommend that all patients with ALL receive know that any progress is because of the treatment
treatment on a clinical trial if possible. Receiving and not because of differences between patients.
treatment on a clinical trial has been shown to
improve outcomes. To join, youll need to review and sign a paper called
an informed consent form. This form describes the
New tests and treatments go through a series of study in detail. The studys risks and benefits should
clinical trials to make sure theyre safe and work. be described and may include others than those
Without clinical trials, there is no way to know if a test described above.
or treatment is safe or helpful. Clinical trials are done
in four steps, called phases. Some examples of the Ask your treatment team if there is an open clinical
four phases of clinical trials for treatment are: trial that you can join. There may be clinical trials
where you are getting treatment or at other treatment
Phase I trials aim to find the best dose and way centers nearby. You can also find clinical trials
to give a new drug with the fewest side effects. through the websites listed in Part 6.
How chemotherapy drugs are given vein in your chest or upper arm. The other end of the
Chemotherapy drugs may be given as a pill that you central line may stay outside of your body. Or, it may
swallow or as a liquid that is injected into your body be attached to a port that is placed just under your
with a needle. When given this way, the drugs travel skin. See Figure 4.1.
in your bloodstream to kill leukemia cells in all parts of
your body. This is called systemic chemotherapy. With a central line, doctors can give IV chemo
treatments without sticking your vein with a needle
Drugs may be injected into a vein, muscle, or under every time. Doctors can also use the central line
your skin. An IV (intravenous) infusion is a slow to give other medicines and take blood samples. A
injection into a vein. The IV infusion may take a few central line can be left in place for weeks or months.
hours. Or, it may be given over several dayscalled
a continuous infusion. An intramuscular injection is Leukemia cells can also spread to the brain
when drugs are given into a muscle. A subcutaneous and spinal cord. This is called CNS disease.
injection is when drugs are given under the skin. Chemotherapy that is injected into a vein cannot
always reach this area. Instead, drugs must be
Often, doctors give IV chemotherapy through a thin, injected directly into the spinal fluid. When drugs are
soft tube called a central venous line or catheter. One given this way, it is called IT (intrathecal) therapy or IT
end of the central line will be inserted into a large chemotherapy. IT chemotherapy is often given during
Figure 4.1
Central venous line and port
Illustration Copyright 2016 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
a lumbar puncture. (See Figure 2.3 on page 22.) to adults. Some patients may develop an allergy to
IT chemotherapy is used to prevent and treat CNS pegaspargase. If this happens, asparaginase erwinia
disease. chrysanthemi may be given instead.
Regimens for AYAs and older adults In contrast, adult regimens tend to use more
A protocol is a detailed outline or plan of a medical cyclophosphamide and anthracyclines such
treatment, study, or procedure. A treatment protocol as doxorubicin and daunorubicin. These drugs
covers all phases of ALL treatment. It states which lower (suppress) the bone marrows ability to
drugs and regimens will be used during each make new blood cells. Thus, they are also called
phase of treatment. A protocol often includes many myelosuppressive drugs. Adult regimens also use
chemotherapy regimens that are given at different allogeneic SCT (stem cell transplant) more often.
times over the course of ALL treatment. (See page 42 for details on this type of treatment.)
Treatments designed for children with ALL are called Dose intensification: Intensified doses of drugs
pediatric protocols. The chemotherapy regimens are given at certain points during treatment for
used for children are often called pediatric regimens. children and adults. But, pediatric protocols give
Likewise, treatments designed for older adults with intensified doses more often throughout the course of
ALL are called adult protocols and adult regimens. treatment.
Many of the same drugs are used for children and In contrast, adult regimens tend to be less intense.
older adults with ALL. But, the doses and schedules The types and doses of drugs used in adult regimens
are different. AYAs are patients aged 15 to 39. are meant to be tolerable for people across a wide
Importantly, studies show that AYAs have much better age range. AYAs treated with these regimens may be
outcomes when treated more like children. under-dosed.
Experts recommend that treatment for AYAs should Length of treatment: In pediatric protocols,
be based on pediatric protocols. This is referred to treatment is given for a longer period of time overall.
as a pediatric-inspired protocol. The main differences CNS preventive treatment is started earlier and given
between pediatric and adult treatments are described longer. Children often receive maintenance therapy
below. for about three years. Adult regimens tend to give
maintenance for about two years.
Differences between pediatric and adult treatment
regimens Side effects of chemotherapy
Drug dosage: Pediatric regimens are more intense A side effect is an unhealthy or unpleasant physical
and complex than those given to older adults. They or emotional condition caused by treatment. Each
use high (intensified) doses of certain chemotherapy treatment for ALL can cause side effects. The
drugs that can be hard for older adults to tolerate. reactions to chemotherapy differ between people.
Drugs used: Pediatric regimens tend to use Some people have many side effects. Others have
more pegaspargase, vincristine, and steroids such few. Some side effects can be very serious while
as dexamethasone and prednisone. Overall, the others can be unpleasant but not serious.
doses of these drugs are higher than what is given
Order of treatments
The treatment of ALL is a long-term process that lasts two to three years. ALL
treatment is given in three main steps, called phases. The length of each phase may
vary based on the intensity of the treatments and other factors.
CONSOLIDATION Maintenance
The second phase of ALL treatment is called The third phase of ALL treatment is called
consolidation. This phase may also be called maintenance. The goal of maintenance
by other names such as intensification or therapy is to keep ALL from coming back.
postremission consolidation. Consolidation Most maintenance drugs are given orally, and
therapy is given once ALL is in remission. patients are usually treated in an outpatient
The goal of consolidation therapy is to kill any setting. The lower doses tend to have less
leukemia cells that may still be in your body. severe side effects. The maintenance phase
During this phase, treatments are intensified. lasts about two to three years. Consolidation
This means that drugs are given in higher doses and maintenance are often jointly called
than during induction. The consolidation phase postremission therapy. Postremission therapy
often lasts for a few months. refers to any treatments given after ALL is in
complete remission.
Most side effects appear soon after treatment starts Not all side effects of chemotherapy are listed here.
and will go away after treatment ends. But, other side Be sure to ask your treatment team for a complete
effects are long-term and may appear years later. list of common and rare side effects. If a side effect
bothers you, tell your treatment team. There may be
The side effects of chemotherapy depend on many ways to help you feel better. There are also ways to
factors. This includes the drug, the dose, and the prevent some side effects.
person. In general, side effects are caused by the
death of fast-growing cells, which are found in the
intestines, mouth, and blood. Thus, common side
effects of chemotherapy are nausea, vomiting,
diarrhea, mouth sores, not feeling hungry, hair loss,
and low blood cell counts. Feeling very tired (fatigue)
is also common.
Treatment response
Even with a complete remission, there may still be a small number of leukemia cells left in the
body that cant be seen with a microscope. This is called MRD (minimal residual disease). Once
ALL is in complete remission, very sensitive tests are used to check for MRD.
After a complete remission, more treatment is needed to kill every last leukemia cell and keep
them from coming back. This is called postremission therapy. A relapse is when ALL comes back
after a complete remission. Sometimes the leukemia cells dont respond to induction therapy.
ALL that is not in complete remission after induction is called refractory ALL.
Tyrosine kinase inhibitors But, each TKI drug works in a slightly different way.
One TKI drug may be able to work against a mutation
TKI (tyrosine kinase inhibitor) therapy is a type of that another TKI cant. Therefore, switching to a
targeted therapy. TKIs are used for a subtype of ALL different TKI may result in a treatment response after
in which the leukemia cells have the Philadelphia a prior TKI stops working.
chromosome. This subtype is called Ph-positive ALL.
The Philadelphia chromosome contains the abnormal Side effects of TKIs
BCR-ABL fusion gene. Some side effects listed below are caused by only
one TKI. Others are caused by all or most TKIs but
TKIs target the abnormal BCR-ABL protein that helps differ in how likely they are to occur. Some common
leukemia cells grow. This protein is made by the side effects of TKIs are low blood cell counts,
BCR-ABL gene. It is a type of protein called a tyrosine abnormal bleeding, fatigue, nausea and vomiting,
kinase. TKIs block (inhibit) the BCR-ABL protein from diarrhea, and stomach or belly pain.
sending the signals that cause too many leukemia
cells to form. These drugs may cause swelling due to fluid buildup
around the eyes or in the hands and feet. Fluid may
TKIs are made in the form of a pill that is swallowed. also collect around the lungs. Other common side
TKIs are typically not used alone to treat ALL. Instead, effects include skin rashes, headaches, and muscle,
a TKI is added to a combination chemotherapy bone, and joint pain. A rare but serious side effect that
regimen. The use of TKIs has greatly improved may happen with TKIs is a change in the rhythm of
treatment outcomes for this type of ALL. your heartbeat.
TKI drug resistance Other rare but serious side effects may be caused by
A treatment response is an improvement in disease certain TKIs. For example, dasatinib may cause fluid
that is caused by treatment. Drug resistance is when buildup around the lungs. Nilotinib may cause the
ALL doesnt respond to a drug. There is more than amount of sugar (glucose) in the blood to be higher
one type of drug resistance. than normal. Serious side effects of ponatinib include
heart problems, blood clots, narrowing of blood
Primary resistance is when ALL doesnt respond vessels, heart attack, and stroke. Liver problems or
at all to a drug taken for the first time. This type of inflammation of the pancreas may also happen.
resistance is rare in ALL. Secondary resistance is
more common. It is when ALL responds to a drug at
first and then stops responding over time.
Conditioning treatment
Before the transplant, you will receive high-dose
chemotherapy and maybe high-dose radiation
therapy. This is called conditioning treatment since
it prepares (conditions) your body to receive the
donated blood stem cells.
greatly weakens your immune system so that your An allogeneic SCT is not used as the first or
body doesnt kill the transplanted blood stem cells. main treatment for ALL. It may be used as part
of consolidation therapy for certain patients with
For some patients, lower doses of chemotherapy or Ph-positive ALL or in patients with other poor risk
radiation may be used before the transplant. This features. Doctors may also consider an allogeneic
is called non-myeloablative or reduced-intensity SCT if prior treatments fail to kill all of the leukemia
conditioning. This type of conditioning may be a good cells or keep them away.
option for certain patients who are older or in poorer
health. It can often work just as well as high-dose Side effects of allogeneic SCT
conditioning. A side effect is an unhealthy or unpleasant physical
or emotional condition caused by treatment. Common
Transplanting the stem cells side effects of chemotherapy, which is given before
After the chemotherapy, the blood stem cells will be the transplant, are described on page 36. You will
put into your body with a transfusion. A transfusion is likely feel tired and weak shortly after the transplant
a slow injection of blood products into a large vein. while waiting for the new blood stem cells to grow in
This process can take several hours to complete. the bone marrow.
The transplanted stem cells then travel to your bone Allogeneic transplants have a high risk of GVHD
marrow and grow. They will make new, healthy blood (graft-versus-host disease). GVHD is when
cells. This is called engraftment. It usually takes about the donated cells see the cells in your body as
2 to 4 weeks. foreign and attack them. The parts of the body
most commonly damaged by GVHD are the skin,
Until then you will have little or no immune defense. intestines, and liver.
This puts you at high risk for infection and bleeding.
You will likely need to stay in a hospital in a very GVHD is a serious side effect that can cause the
clean room for some time. It may take a few weeks transplant to fail by stopping the donated blood stem
or months for blood cells to fully recover so that your cells from growing in your bone marrow. GVHD can
immune system is back to normal. happen within a few weeks after the transplant or
much later. Your doctor may give you medicine that
Considering allogeneic SCT suppresses your immune system to try to prevent this
An allogeneic SCT is a complex treatment and can side effect.
cause very serious side effects. Thus, it may not
be a good treatment choice for every patient with
ALL. Many treatment centers will only consider this
treatment option for patients younger than 65 years
of age.
Radiation therapy
Radiation therapy uses high-energy rays to treat
cancer. The rays damage the genes in cells. This
either kills the cancer cells or stops new cancer cells
from being made. Radiation therapy may be given
in different ways. For ALL, radiation therapy is given
from a machine outside the body. This method is
called EBRT (external beam radiation therapy).
Skin changes,
Hair loss,
Fatigue,
Upset stomach, and
Diarrhea.
Review
Treatment for ALL is given in steps, called A clinical trial studies a test or treatment
phases: induction, consolidation, and to see how safe it is and how well it
maintenance. works. Clinical trials are how we learn
which treatments are best. NCCN experts
CNS preventive treatment is given during all
recommend that you should strongly consider
phases of treatment.
taking part in a clinical trial if one is available
The main treatment of ALL involves long-term to you.
use of chemotherapy.
Treatment for AYA patients should be based
Chemotherapy is treatment with drugs that on regimens which have been highly effective
kill fast-growing cells, including leukemia cells for children with ALL.
and normal cells.
Supportive care is treatment given to relieve
Targeted therapy drugs specifically target the symptoms of cancer or side effects of
cancer cells. cancer treatment. Supportive care is an
important part of overall cancer treatment.
A stem cell transplant replaces damaged or
diseased bone marrow with healthy donor
blood stem cells.
Clinical trial,
Complete remission Monitor for MRD
Pediatric-inspired chemotherapy
regimen (preferred), or
Other multiagent Less than complete remission Treatment for refractory ALL
chemotherapy regimen
Chart 5.1.1 shows the induction therapy options A regimen based on treatment designed for children
for AYAs with Ph-negative ALL. Induction therapy is with ALL is preferred. This is called a pediatric-
the first phase of treatment for ALL. It is also called inspired regimen or a pediatric-inspired protocol. But,
remission induction. The goal is to kill all of the other multiagent chemotherapy regimens that have
leukemia cells in your bone marrow and put ALL into been studied in AYAs may also be used.
complete remission.
Pediatric-inspired induction regimens tend to use a
Induction therapy consists of high doses of combination of vincristine, pegaspargase, a steroid
chemotherapy drugs. It is very intensive and lasts (prednisone or dexamethasone), and an anthracycline
about four weeks (one month). You may need to stay (doxorubicin or daunorubicin). Some regimens may
in the hospital for some or all of the time during this also include cyclophosphamide and etoposide. (See
treatment. page 34 to read more about chemotherapy drugs.)
Chart 5.1.2 shows the treatment options for AYAs multiagent chemotherapy as outlined in the pediatric-
with Ph-negative ALL in complete remission after inspired regimen. This may be an especially good
induction therapy. Consolidation therapy is the second choice if no leukemia cells were found by MRD
phase of treatment for ALL. The goal of this phase is testing.
to kill any leukemia cells that may still be in your body.
It is followed by maintenance therapy. These phases Consolidation therapy may include combinations of
are jointly referred to as postremission therapy since drugs similar to those used for induction. In pediatric-
they are given after ALL is in remission. inspired regimens, it tends to include high-dose
methotrexate, cytarabine, 6-MP, and pegaspargase.
Your doctor will look at many factors to help plan Chemotherapy drugs are given in higher (intensified)
consolidation therapy. This includes the ALL cell doses during consolidation. CNS preventive treatment
subtype, chromosome changes, results of MRD is also usually given throughout this phase of
testing, and other prognostic factors. Your general treatment.
health, current symptoms, and side effects will
also be considered. This can help to decide if you Consolidation therapy may last several months.
need and can tolerate more intensive treatment for How long it lasts and the total number of cycles
consolidation. varies based on the regimen used. The full treatment
regimen should be followed all the way through
consolidation and to the end of maintenance.
Consolidation therapy options
The other option is to consider an allogeneic SCT.
There are two main options to choose from for This is a very intensive treatment performed in
consolidation therapy. The first option is to stay on specialized centers, and may not be a good choice
Chart 5.2.1 Remission induction for older adults with Ph-negative ALL
Clinical trial,
Complete remission, monitor for MRD
Patients 65 years of age
Multiagent chemotherapy
or patients with other
regimen for adults, or
serious health problems
Less than complete remission
Corticosteroids
Chart 5.2.1 shows the induction therapy options for CNS treatment may include IT methotrexate alone
older adults with Ph-negative ALL. Induction therapy or with other drugs such as IT cytarabine and an IT
is the first phase of treatment for ALL. It is also called steroid (dexamethasone or prednisone). When all
remission induction. The goal is to kill all of the three drugs are given, it is called triple IT therapy.
leukemia cells in your bone marrow and put ALL into Methotrexate, cytarabine, and 6-MP may also be
complete remission. given as IV injections for CNS treatment. Rarely, CNS
disease may be found when ALL is first diagnosed.
Induction therapy consists of high doses of In this case, your doctor may consider giving cranial
chemotherapy drugs. It is very intensive and lasts irradiation as well.
about four weeks (one month). You may need to stay
in the hospital for some or all of the time during this
treatment. Induction therapy options
CNS preventive treatment is given to all patients Often, age 65 is the cut-off for intensive treatment.
during the induction phase. For CNS treatment, drugs But, age alone is not a good gauge of a persons
are often injected into the spinal fluid during a lumbar overall health or fitness for intensive treatment. When
puncture. When drugs are given this way, it is called choosing an induction regimen, your doctors will
IT therapy or IT chemotherapy. look at your age, general health, organ function, and
other current health conditions. This will help your If tests show a complete remission, then your
doctor to know if you are able to receive very strong doctor may test for MRD. MRD is when a very small
treatments. amount of leukemia cells remains in your body
after a course of treatment. With MRD, the amount
If you are younger than age 65, or you dont have of leukemia cells left is too small to be seen with a
other serious health problems, there are two main microscope.
options to choose from. Treatment within a clinical
trial is preferred if one is open and is the right fit PCR and flow cytometry are very sensitive tests that
for you. The other option is to receive multiagent doctors use to check for MRD. These tests can detect
chemotherapy based on a regimen designed for a single leukemia cell among more than 10,000
adults. Induction regimens for adults tend to use a normal cells. They can be done on a sample of blood
combination of vincristine, a steroid (prednisone or or bone marrow. But, bone marrow is preferred.
dexamethasone), cyclophosphamide, and doxorubicin Testing for MRD can help your doctor decide if more
or daunorubicin. intensive treatments are needed for consolidation.
If you are age 65 or older, or you have other If tests show less than a complete remission, this
serious health problems, there are three main means treatment wasnt able to kill enough leukemia
options to choose from. Treatment within a clinical cells in your body. ALL that is not in complete
trial is preferred if one is open and is the right fit remission after induction is called refractory ALL. In
for you. The second option is to have multiagent this case, treatment with other drugs or regimens will
chemotherapy based on a regimen for adults as be tried. See Next steps at the end of this section.
described above. The third option is treatment
with corticosteroids such as prednisone or
dexamethasone. These drugs may be easier to take
than chemotherapy. Some patients may not be able
to tolerate the side effects of intensive (high-dose)
regimens. If needed, some chemotherapy drugs may
Next steps:
be given in lower doses to lessen the side effects.
If induction therapy resulted in a
complete remission, see Chart 5.2.2
Response
on page 56 for the next options. If
At the end of induction, your doctor will assess how induction therapy resulted in less than
well treatment worked. A treatment response is an
outcome or improvement caused by treatment. To
a complete remission, see Chart 5.6.1
check the response, your doctor will test a sample on page 68 for the next options.
of blood and bone marrow with a microscope. A
complete remission is when no leukemia cells are
seen in the blood or bone marrow and all signs and
symptoms of ALL are gone. (See page 39 for more
details about treatment responses.)
Chart 5.2.2 shows the treatment options for older need and can tolerate more intensive treatment for
adults with Ph-negative ALL in a complete remission consolidation.
after induction therapy. Consolidation therapy is the
second phase of treatment for ALL. The goal of this If you are younger than age 65, or you dont have
phase is to kill any leukemia cells that may still be other serious health problems, there are two main
in your body. It is followed by maintenance therapy. options to choose from. One option is to stay on the
These phases are jointly referred to as postremission multiagent chemotherapy regimen for consolidation
therapy since they are given after ALL is in remission. and maintenance. This may be an especially good
choice if no leukemia cells were found by MRD
testing.
Consolidation therapy options
Consolidation therapy may include combinations of
Your doctor will look at many factors to help plan drugs similar to those used for induction. In regimens
consolidation therapy. This includes the ALL cell designed for adults, it tends to include drugs such as
subtype, chromosome changes, results of MRD methotrexate, cytarabine, and 6-MP. Chemotherapy
testing, and other factors described in Part 3. Your drugs are given in higher (intensified) doses during
general health, current symptoms, and side effects consolidation. CNS preventive treatment is also
will also be noted. This can help to decide if you usually given throughout this phase of treatment.
Consolidation therapy may last several months. After consolidation with multiagent
How long it lasts and the total number of cycles chemotherapy, you will receive maintenance
varies based on the regimen used. The full treatment therapy. Maintenance therapy is the third phase of
regimen should be followed all the way through ALL treatment. Maintenance therapy is given to keep
consolidation and to the end of maintenance. up (maintain) the good results of prior treatments.
The goal is to prevent a relapse after induction and
The other option is to consider an allogeneic SCT. consolidation therapy. A relapse is when leukemia
This is a very intensive treatment performed in cells come back after a complete remission.
specialized centers, and may not be a good choice
for everyone. It can cause very severe side effects Most maintenance regimens are based on a
that may be too much for some patients to take. Your backbone of daily 6-MP and weekly methotrexate.
doctor will look at a number of factors to assess if Often, vincristine and a steroid (prednisone or
an allogeneic SCT is a good choice for you. This dexamethasone) are also given. Maintenance therapy
includes your age, general health, and if you can drugs are often given in lower doses and cause fewer
tolerate intensive treatments. (See page 42 to read side effects. CNS preventive treatment can also be
more about allogeneic SCT.) given throughout the maintenance phase.
Your doctor may consider this option if tests found In general, maintenance therapy is given for about
MRD after induction. This may also be a good choice two to three years. But, the total length varies based
if the leukemia cells have certain poor risk features. on the treatment regimen used. Adult regimens tend
A poor risk feature is something that increases the to give maintenance therapy for a shorter amount of
chance that ALL might come back after treatment. time than pediatric-inspired regimens.
Examples of poor risk features include having less
than the normal number of chromosomes or having
five or more abnormal chromosome changes.
Multiagent chemotherapy
regimen + TKI
Less than complete remission Treatment for refractory ALL
Chart 5.3.1 shows the induction therapy options TKIs are a type of targeted therapy. TKIs block the
for AYAs with Ph-positive ALL. Induction therapy is cancer-causing action of the BCR-ABL fusion gene.
the first phase of treatment for ALL. It is also called This gene is found on the Philadelphia chromosome.
remission induction. The goal is to kill all of the The use of TKIs has greatly improved treatment
leukemia cells in your bone marrow and put ALL into outcomes for Ph-positive ALL. Importantly, adding
complete remission. a TKI to the multiagent chemotherapy regimen
increases the chance of a complete remission. (See
Induction therapy consists of high doses of page 40 to read more about TKIs.)
chemotherapy drugs. It is very intensive and lasts
about four weeks (one month). You may need to stay Induction regimens for AYAs generally include a
in the hospital for some or all of the time during this combination of vincristine, pegaspargase, a steroid
treatment. (prednisone or dexamethasone), and an anthracycline
(doxorubicin or daunorubicin). Some regimens may
also include cyclophosphamide and etoposide.
Induction therapy options
CNS preventive treatment is given to all patients
In general, there are two main options to choose from during the induction phase. For CNS treatment, drugs
for induction therapy. Treatment within a clinical trial is are often injected into the spinal fluid during a lumbar
preferred if one is open and is the right fit for you. The puncture. When drugs are given this way, it is called
other option is to have a multiagent chemotherapy IT therapy or IT chemotherapy.
regimen combined with a TKI. Imatinib and dasatinib
are the main TKIs used for induction. CNS treatment may include IT methotrexate alone
or with other drugs such as IT cytarabine and an IT
Chart 5.3.2 shows the treatment options for AYAs Consolidation therapy options
with Ph-positive ALL in complete remission after
induction therapy. Consolidation therapy is the second There are two main options for consolidation
phase of treatment for ALL. The goal of this phase is therapy. The first option is to have an allogeneic
to kill any leukemia cells that may still be in your body. SCT. This option is recommended if a well-matched
It is followed by maintenance therapy. These phases donor has been found. Consolidation with an
are jointly referred to as postremission therapy since allogeneic SCT may help keep ALL from coming
they are given after ALL is in remission. back after a complete remission. But, it is a very
intensive treatment and may not be a good choice
Your doctor will look at many factors to help plan for everyone. (See page 42 to read more about
consolidation therapy. This includes the ALL cell allogeneic SCT.)
subtype, chromosome changes, results of MRD
testing, and other prognostic factors. Your general Your doctor will look at a number of factors to decide
health, current symptoms, and side effects will also if an allogeneic SCT is a good choice for you. This
be noted. This can help to decide if you need and can includes your age, prognostic factors, and how well
tolerate more intensive treatment for consolidation. prior treatments worked. For some AYA patients, an
allogeneic SCT may offer the best chance of a long-
lasting remission. For other patients, an allogeneic
SCT might not be better than chemotherapy and a
TKI.
The second option is to stay on multiagent (prednisone or dexamethasone) are also given. A TKI
chemotherapy combined with a TKI. This option is such as imatinib or dasatinib should be added to the
suggested if a well-matched donor for the SCT has maintenance regimen your doctor plans for you.
not been found. This may also be a good option if
your doctor thinks an allogeneic SCT is too intense After consolidation with an allogeneic SCT,
for you. maintenance therapy with a TKI is recommended.
The TKI may be given alone. Or, it may be given
Consolidation therapy may include combinations of along with other drugs if the side effects arent too
drugs similar to those used for induction. A TKI should severe.
be added to the consolidation therapy regimen for all
patients with Ph-positive ALL. Imatinib and dasatinib Methotrexate and 6-MP can affect the liver and lower
are the main TKIs used for this phase. Staying on (suppress) the bone marrows ability to make new
treatment with a TKI can help keep ALL from coming blood cells. These side effects can be severe and
back after a complete remission. hard to tolerate. If needed, lower doses of these
drugs may be given to lessen the side effects.
Chemotherapy drugs are given in higher (intensified)
doses during consolidation. CNS preventive treatment Maintenance therapy drugs are often given in lower
is also usually given throughout this phase of doses and cause fewer side effects. CNS preventive
treatment. Consolidation therapy may last several treatment can also be given throughout this treatment
months. How long it lasts and the total number of phase. Maintenance therapy is given for about two
cycles varies based on the regimen used. The full to three years. But, the total length varies based on
treatment regimen should be followed all the way the regimen used. Pediatric-inspired regimens tend to
through consolidation and to the end of maintenance. give maintenance therapy for a longer time than adult
regimens.
Chart 5.4.1 Remission induction for older adults with Ph-positive ALL
Patients <65 years Clinical trial, or Complete remission, monitor for MRD
of age or patients
with no other serious
Multiagent chemotherapy
health problems Less than complete remission
regimen + TKI
Clinical trial,
Patients 65 years Complete remission, monitor for MRD
of age or patients
TKI + corticosteroids, or
with other serious
health problems Less than complete remission
TKI + chemotherapy
Chart 5.4.1 shows the induction therapy options for steroid (dexamethasone or prednisone). When all
older adults with Ph-positive ALL. Induction therapy three drugs are given, it is called triple IT therapy.
is the first phase of treatment for ALL. It is also called Methotrexate, cytarabine, and 6-MP may also be
remission induction. The goal is to kill all of the given as IV injections for CNS treatment. Rarely, CNS
leukemia cells in your bone marrow and put ALL into disease may be found when ALL is first diagnosed.
complete remission. In this case, your doctor may consider giving cranial
irradiation as well.
Induction therapy consists of high doses of
chemotherapy drugs. It is very intensive and lasts
about four weeks. You may need to stay in the Induction therapy options
hospital some or all of the time during this treatment.
Often, age 65 is the cut-off for intensive treatment.
CNS preventive treatment is given to all patients But, age alone is not a good gauge of a persons
during the induction phase. For CNS treatment, drugs overall health or fitness for intensive treatment. When
are often injected into the spinal fluid during a lumbar choosing an induction regimen, your doctors will
puncture. When drugs are given this way, it is called look at your age, general health, organ function, and
IT therapy or IT chemotherapy. other current health conditions. This will help your
doctor to know if you are able to receive very strong
CNS treatment may include IT methotrexate alone treatments.
or with other drugs such as IT cytarabine and an IT
If you are younger than age 65, or you dont seen in the blood or bone marrow and all signs and
have other serious health problems, there are symptoms of ALL are gone. (See page 39 for more
two main options to choose from. Treatment within a details about treatment responses.)
clinical trial is preferred if one is open and is the right
fit for you. The other option is to have a multiagent If tests show a complete remission, then your
chemotherapy regimen combined with a TKI. Imatinib doctor will test for MRD. MRD is when a very small
and dasatinib are the main TKIs used for induction. amount of leukemia cells remains in your body
after a course of treatment. With MRD, the amount
TKIs are a type of targeted therapy. TKIs block the of leukemia cells left is too small to be seen with a
cancer-causing action of the BCR-ABL fusion gene. microscope.
This gene is found on the Philadelphia chromosome.
The use of TKIs has greatly improved treatment PCR and flow cytometry are very sensitive tests that
outcomes for Ph-positive ALL. Importantly, adding doctors use to check for MRD. These tests can detect
a TKI to the multiagent chemotherapy regimen a single leukemia cell among more than 10,000 normal
increases the chance of a complete remission. (See cells. They can be done on a sample of blood or bone
page 40 to read more about TKIs.) marrow. But, bone marrow is preferred. Testing for
MRD can help your doctor decide if more intensive
If you are age 65 or older, or you have other treatments are needed for consolidation therapy.
serious health problems, there are three main
options to choose from. Treatment within a clinical trial If tests show less than a complete remission, this
is preferred if one is open and is the right fit for you. means treatment wasnt able to kill enough leukemia
The second option is to have treatment with a TKI cells in your body. ALL that is not in complete
(imatinib or dasatinib) and a steroid. Prednisone and remission after induction is called refractory ALL. In
dexamethasone are the main steroids that may be this case, treatment with other drugs or regimens will
used. The third option is to receive a TKI along with a be tried. See Next steps at the end of this section.
multiagent chemotherapy regimen.
Allogeneic SCT if a
Consider maintenance with a TKI
donor is available, or
Patients <65 years
of age or patients
Maintenance therapy with:
with no other serious
If allogeneic SCT donor is not TKI (imatinib or dasatinib),
health problems
available, continue multiagent Monthly vincristine/prednisone pulses,
chemotherapy regimen + TKI Weekly methotrexate, and
Daily 6-MP
Chart 5.4.2 shows the treatment options for older If you are younger than age 65, or you dont have
adults with Ph-positive ALL after induction therapy other serious health problems, there are two main
resulted in a complete remission. Consolidation options to choose from. The first option is to have an
also called intensificationis the second phase of allogeneic SCT. This option is recommended if a well-
treatment for ALL. This may also be referred to as matched donor has been found. Consolidation with
postremission therapy since it is given after ALL is in an allogeneic SCT may help keep ALL from coming
complete remission. The goal of consolidation is to kill back after a complete remission. But, it is a very
any leukemia cells that may still be in your body. intensive treatment that may not be a good choice
for everyone. (See page 42 to read more about an
allogeneic SCT.)
Consolidation therapy
Your doctor will look at a number of factors to decide
Your doctor will look at many factors to help plan if an allogeneic SCT is a good choice for you. This
consolidation therapy. This includes the ALL cell includes your age, general health, and ability to
subtype, chromosome changes, results of MRD tolerate intensive treatments. For some patients, an
testing, and other prognostic factors. Your general allogeneic SCT may offer the best chance of a long-
health, current symptoms, and side effects will also lasting remission.
be noted. This can help to decide if you need and can
tolerate more intensive treatment for consolidation. The second option is to stay on the multiagent
chemotherapy regimen and TKI. This option is
suggested if a well-matched donor for the SCT has Staying on treatment with a TKI is a key part of
not been found. This may also be a good option if your maintenance therapy. Most maintenance regimens
doctor thinks an allogeneic SCT is too intense for you. include weekly methotrexate and daily 6-MP.
Often, monthly pulses of vincristine and a steroid
Consolidation therapy may include combinations of (prednisone or dexamethasone) are also given. A TKI
drugs similar to those used for induction. A TKI should such as imatinib or dasatinib should be added to the
be added to the consolidation therapy regimen for all maintenance regimen your doctor plans for you.
patients with Ph-positive ALL. Imatinib and dasatinib
are the main TKIs used for this phase. Staying on After consolidation with an allogeneic SCT,
treatment with a TKI can help keep ALL from coming maintenance therapy with a TKI is often
back after a complete remission. recommended. The TKI may be given alone. Or, other
drugs may also be given if side effects arent too
Often, chemotherapy drugs are given in higher severe.
(intensified) doses during consolidation. CNS
preventive treatment can also be given throughout this Methotrexate and 6-MP can affect the liver and lower
phase of treatment. Consolidation therapy may last the bone marrows ability to make new blood cells.
several months. How long it lasts and the total number These side effects can be severe and hard to tolerate.
of cycles varies based on the regimen used. The full If needed, lower doses of these drugs may be given
treatment regimen should be followed all the way to lessen the side effects.
through consolidation and to the end of maintenance.
Maintenance therapy drugs are often given in lower
If you are age 65 or older, or you have other doses and cause fewer side effects. CNS preventive
serious health problems, there are two main treatment can also be given throughout this treatment
options to choose from. A key part of both options phase. Maintenance therapy is given for about two
is to continue treatment with a TKI. Imatinib and to three years. But, the total length varies based
dasatinib are the main TKIs that may be used. The on the regimen used. Adult regimens tend to give
first option is to keep taking the TKI with or without maintenance therapy for a shorter amount of time
steroids such as prednisone or dexamethasone. The than pediatric-inspired regimens.
second option is to keep taking the TKI with or without
chemotherapy.
Chart 5.5 shows the tests that are recommended Follow-up tests
after completing the entire treatment regimen,
including induction, consolidation, and maintenance. The suggested schedule of follow-up tests is shown
Follow-up tests are given after treatment to check in Chart 5.5. Many of the tests used to diagnose ALL
how well treatment worked. and plan treatment are repeated during follow-up.
It is important for treatment to kill all of the leukemia During the first year of follow-up, a physical exam
cells and keep them away. Doctors use follow-up should be done once a month. The physical exam
tests to look for signs of cancer return (relapse) after gives your doctor an idea about your general health.
treatment. These tests also check how well your For males, it should include a testicular exam.
organs and body systems are working. This is needed
since ALL and its treatment can cause much damage. A CBC with differential should also be done once a
month during the first year of follow-up. This test will
show if there is normal number of each type of blood
cell.
Clinical trial,
Allogeneic SCT
CNS preventive treatment. The options for treating of vincristine. This allows doctors to give higher doses
relapsed and refractory ALL are described next. of the drug without increasing side effects.
Treatment within a clinical trial is preferred if one is Another option for patients with B-cell ALL is to have
open and is the right fit for you. A clinical trial is a a regimen that includes clofarabine. Clofarabine
type of research that studies how safe and helpful a is approved for patients aged 21 or younger. But,
treatment is. If you arent able to join a clinical trial, adults may also benefit from regimens with this
there are a few other choices. chemotherapy drug.
A second option is to have a different induction An allogeneic SCT is also an option to consider if a
regimen than you had before. ALL that relapses matched donor has been found. In this case, your
more than three years after diagnosis is called a late doctor will assess if you are healthy enough to have
relapse. For AYAs with a late relapse, treatment with an allogenic SCT. Some patients may not be able to
the same induction regimen used before is an option tolerate this intensive treatment. This is especially
to consider. true for older adults who may have other health
problems.
Another option is to have chemotherapy for relapsed
or refractory ALL. There are many drugs and drug If ALL relapses after an initial allogeneic SCT, a
combinations to choose from. These are listed in the second allogeneic SCT is an option. Or your doctor
bottom of Chart 5.6.1. Blinatumomab is the preferred may consider a donor lymphocyte infusion. For this
option for B-cell ALL. Blinatumomab is a type of treatment, you will be given white blood cells called
targeted therapy called a monoclonal antibody. It uses lymphocytes from the same donor used for the SCT.
the immune system to help kill leukemia cells. (See
page 41 for details.)
Clinical trial,
TKI alone,
Consider BCR-ABL
TKI chemotherapy,
gene mutation testing
TKI corticosteroids, or
Allogeneic SCT
and side effects. This helps your doctor to know if you An allogeneic SCT is also an option if you are healthy
are healthy enough to receive strong treatments. enough and a well-matched donor has been found.
Some patients may not be able to tolerate this
intensive treatment. This is especially true for older
Treatment options adults who may have other health problems.
There are several treatment options to choose If ALL relapses after the first allogeneic SCT, a
from. But, any treatment given should include second allogeneic SCT is an option. Or your doctor
CNS preventive treatment. The options for treating may consider a donor lymphocyte infusion. For this
relapsed and refractory ALL are described next. treatment, you are given white blood cells called
lymphocytes from the same donor used for the SCT.
Treatment within a clinical trial is preferred if one is
open and is the right fit for you. A clinical trial is a
type of research that studies how safe and helpful a
treatment is. If you arent able to join a clinical trial,
there are a few other choices.
My notes
4. What is the ALL cell subtype and cytogenetic subtype? What does this mean for me and my
treatment options?
9. Would you give me a copy of the pathology report and other test results?
10. 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?
5. Do your suggested options include clinical trials? Please explain why. What kinds of treatments
would the clinical trial involve? Is it specifically for people my age?
8. 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?
9. 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?
10. What can be done to prevent or relieve the side effects of treatment?
11. Are there supportive services that I can get involved in? Support groups?
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? Does this differ if I have
treatment on a clinical trial?
3. How many patients like me have you treated? How many of them were my age?
4. How many treatments or procedures like the one youre suggesting have you done?
7. Are you involved in any clinical trials for the treatment of ALL? For people my age?
8. Does your hospital have a program specifically for people my age with cancer?
2nd opinion
The time around a cancer diagnosis can be very
stressful. People with cancer often want to start
treatment as soon as possible. They want to make
the cancer go away before it spreads farther. While
cancer cant be ignored, there is time to think about your options. Choosing your cancer treatment is a
and choose which option is best for you. very important decision. It can affect your length and
quality of life.
You may wish to have another doctor review your test
results and suggest a treatment plan. This is called Support groups
getting a 2nd opinion. You may completely trust your Besides talking to health experts, it may help to talk
doctor, but a 2nd opinion on which option is best can to patients who have walked in your shoes. Support
help. groups often consist of people at different stages of
treatment. Some may be in the process of deciding
Copies of all of the test results need to be sent to while others may be finished with treatment. At
the doctor giving the 2nd opinion. Some people feel support groups, you can ask questions and hear
uneasy asking for copies from their doctors. However, about the experiences of other people with ALL.
a 2nd opinion is a normal part of cancer care.
Compare benefits and downsides
When doctors have cancer, most will talk with more Every option has benefits and downsides. Consider
than one doctor before choosing their treatment. these when deciding which option is best for you.
What's more, some health plans require a 2nd opinion. Talking to others can help identify benefits and
If your health plan doesnt cover the cost of a 2nd downsides you havent thought of. Scoring each
opinion, you have the choice of paying for it yourself. factor from 0 to 10 can also help since some factors
may be more important to you than others.
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
www.cancer.gov/types/aya
Stupid Cancer
www.stupidcancer.org
Dictionary
Acronyms
Dictionary
acute lymphoblastic leukemia (ALL) blood cell count
A fast-growing cancer that causes too many immature white The number of blood cells in a sample of blood.
blood cells called lymphoblasts to be made.
blood chemistry profile
adolescents and young adults (AYAs) A test that measures the amount of chemicals in the blood
Patients who are 15 to 39 years of age. to look for signs of disease and check how well organs are
working.
allogeneic stem cell transplant (SCT)
A treatment in which the patient receives immature blood- blood stem cell
forming cells (blood stem cells) from another person to An immature cell from which all other types of blood cells are
replace damaged or diseased cells in the bone marrow. made.
anesthesia bloodstream
Loss of feeling with or without loss of wakefulness caused by Blood that flows throughout the body in small tubes called
drugs. blood vessels.
anthracycline B-lymphocyte
A cancer drug that damages and disrupts the making of DNA One of two main types of white blood cells called
in cells. lymphocytes that help protect the body from infection and
disease.
B-cell
One of two main types of white blood cells called bone marrow
lymphocytes that help protect the body from infection and The soft, sponge-like tissue in the center of most bones
disease. Also called B-lymphocyte. where blood cells are made.
prognosis spleen
The likely or expected course, pattern, and outcome of a An organ to the left of the stomach that helps protect the
disease based on tests. body from disease.
Acronyms
6-MP MRI
6-mercaptopurine magnetic resonance imaging
ALL PCR
acute lymphoblastic leukemia polymerase chain reaction
AYA PET
adolescent and young adult positron emission tomography
CBC Ph-negative
complete blood count Philadelphia chromosome negative
CNS Ph-positive
central nervous system Philadelphia chromosome positive
CT SCT
computed tomography stem cell transplant
DNA TKI
deoxyribonucleic acid tyrosine kinase inhibitor
EBRT TLS
external beam radiation therapy tumor lysis syndrome
FDA VSLI
U.S. Food and Drug Administration vincristine sulfate liposome injection
FISH
fluorescence in situ hybridization
NCCN Abbreviations and Acronyms
GVHD
graft-versus-host disease NCCN
National Comprehensive Cancer Network
GVL
graft-versus-leukemia NCCN Patient Guidelines
HLA NCCN Guidelines for Patients
human leukocyte antigen
NCCN Guidelines
IT NCCN Clinical Practice Guidelines in Oncology
intrathecal
IV
intravenous
MRD
minimal residual disease
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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Lloyd E. Damon, MD
UCSF Helen Diller Family
Comprehensive Cancer Center
My notes
Index
adolescent and young adult (AYA) 28, 36, 46, 4853, targeted therapy 40, 41, 46, 58, 63, 69
5861, 69, 75 tyrosine kinase inhibitor (TKI) 40, 41, 58, 6065, 70, 71
BCR-ABL gene 20, 21, 40, 58, 63, 70
bone marrow 4, 69, 12, 15, 16, 1821, 24, 36, 37, 39, 42,
43, 45, 46, 50, 51, 54, 55, 58, 59, 6163, 6567
bone marrow aspiration 18, 24, 66, 67
bone marrow biopsy 18, 24
central nervous system (CNS) 3537, 44, 46, 5054,
5659, 61, 62, 65, 67, 69, 71
chemotherapy 3438, 40, 42, 43, 45, 46, 50, 5258,
6065, 6871
chromosome 8, 1921, 24, 27, 29, 30, 40, 48, 49, 52, 53,
5658, 60, 63, 64, 68, 70
clinical trial 33, 46, 49, 50, 54, 55, 58, 62, 63, 6871, 75
consolidation 37, 43, 46, 5153, 5557, 5961, 6366
follow-up 52, 53, 56, 57, 61, 6567
imaging test 23, 67
induction 37, 39, 46, 5066, 6871
intrathecal (IT) chemotherapy 35, 36, 50, 54, 58, 62
lumbar puncture 15, 22, 36, 50, 54, 58, 62, 66, 67
maintenance 36, 37, 46, 52, 53, 56, 57, 60, 61, 6466
multidisciplinary team 49, 75
older adult 28, 36, 48, 49, 5457, 6265, 69, 71
Philadelphia chromosome 20, 21, 27, 29, 40, 48, 49, 58,
63, 68, 70
protocol 36, 50
refractory 39, 48, 50, 51, 55, 58, 59, 63, 6870
regimen 34, 36, 40, 42, 46, 5071, 75
relapse 39, 48, 53, 57, 61, 6571
remission 37, 39, 48, 5068, 70
response 39, 40, 50, 51, 54, 55, 58, 59, 62, 63, 68, 70
side effect 16, 28, 33, 3638, 4046, 52, 53, 5557, 6065,
68, 69, 71
stem cell transplant (SCT) 36, 4244, 52, 53, 56, 57, 60,
61, 64, 65, 6871
subtype 27, 29, 30, 40, 49, 52, 56, 60, 64
Acute Lymphoblastic
Leukemia
Version 1.2016
NCCN Foundation gratefully acknowledges our industry supporter Pfizer, Inc. for its 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-0919-0616