Understanding Acute Lymphoblastic Leukemia

Available online at NCCN.org/patients
Acute
Lymphoblastic
Leukemia
NCCN Guidelines for Patients® Version 2.2014
Please
com
plete
our
online
survey at
NCCN.org/patients/survey

1NCCN Guidelines for Patients®
Acute Lymphoblastic Leukemia, Version 2.2014
NCCN Guidelines for Patients®
Version 2.2014
Acute Lymphoblastic Leukemia
Learning that you have cancer can be overwhelming. The goal of this book
is to help you get the best care. It explains which tests and treatments are
recommended by experts in acute lymphoblastic leukemia.
The National Comprehensive Cancer Network®
(NCCN®
) is a not-for-profit
alliance of 26 of the world’s leading cancer centers. Experts from NCCN®
have
written treatment guidelines for leukemia doctors. These treatment guidelines
suggest what the best practice is for cancer care. The information in this
patient book is based on the guidelines written for doctors.
This book focuses on the treatment of acute lymphoblastic leukemia. NCCN
also offers patient books on breast, ovarian, and pancreatic cancer, as well as
many other cancer types. Visit NCCN.org/patients for the full library of patient
books as well as other patient and caregiver resources.

1 About acute lymphoblastic leukemia Genetic counseling | Treatment
Credits
NCCN staff involved in making the guidelines for patients and doctors include:
NCCN Patient Guidelines
Dorothy A. Shead, MS
Director, Patient and Clinical
Information Operations
Laura J. Hanisch, PsyD
Medical Writer/
Patient Information Specialist
Lacey Marlow
Associate Medical Writer
NCCN Guidelines
Kristina M. Gregory, RN, MSN, OCN
Vice President/
Clinical Information Operations
Courtney Smith, PhD
Oncology Scientist/
Medical Writer
NCCN Marketing
Susan Kidney
Graphic Design Specialist
NCCN Drugs & Biologics Programs
Rachael Clarke
Medical Copyeditor
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 Patient Guidelines®
. 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
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.
Supported by the NCCN Foundation®
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.
© 2014 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.
National Comprehensive Cancer Network (NCCN)
275 Commerce Drive • Suite 300
Fort Washington, PA 19034
215.690.0300

Contents
Acute Lymphoblastic Leukemia
4 How to use this book
5 Part 1
About acute lymphoblastic
leukemia
Explains how and where this type of
blood cancer starts.
11 Part 2
Overview of tests
Describes the tests used to confirm
acute lymphoblastic leukemia and plan
treatment.
21 Part 3
Treatment planning
Explains the main factors doctors use to
plan treatment that’s right for you.
27 Part 4
Overview of cancer
treatments
Describes the types of treatments for acute
lymphoblastic leukemia.
37 Part 5
Side effects and
supportive care
Describes the health problems caused by
cancer and its treatment along with ways
to manage them.
43 Part 6
Treatment guide
Presents the recommended course of
action from diagnosis to after cancer
treatment.
71 Part 7
Making treatment decisions
Offers tips to help you talk with your
doctors and get a treatment plan that
meets all your needs.
83 Glossary:
84 Dictionary
90 Acronyms
93 NCCN Panel Members
94 NCCN Member Institutions
96 Index

How to use this book
Who should read this book?
Leukemia is a type of cancer that starts in
blood-forming cells in the bone marrow. Acute
lymphoblastic leukemia is a fast-growing type
of leukemia that causes too many immature
blood cells called lymphoblasts to be made.
People diagnosed with this type of leukemia and
those who support them—caregivers, family,
and friends—may find this book helpful. The
information in this book may help you talk with
your treatment team, understand what doctors
say, and prepare for treatment.
Does the whole book
apply to me?
This book includes information for many
situations. Thus, not everyone will get every test
and treatment listed. Your treatment team can
point out what applies to you and give you more
information. As you read through this book, you
may find it helpful to make a list of questions to
ask your doctors.
This book includes the recommendations that
NCCN experts agree are most useful. However,
each patient is unique and these specific
recommendations may not be right for you. Your
doctors may suggest other tests or treatments
based on your health and other factors. This
book does not replace the knowledge and
suggestions of your doctors.
Making sense of medical
terms
In this book, many medical words are included
that describe cancer, tests, and treatments.
These are words that you will likely hear from
your treatment team. Some of this information
may be new to you, and it may be a lot to learn.
Keep reading and review the information. Be
sure to ask your treatment team to explain a
word or phrase that you don’t understand.
Words and acronyms that you may not know are
defined in the text or underlined when first used
on a page. All underlined words are defined
in the Glossary. Acronyms are also listed and
defined in the Glossary. Acronyms are words
formed from the first letters of other words. One
example is CBC for complete blood count.

3
Ductal carcinoma in situ
5
1
About acute
lymphoblastic leukemia

Learning that you have cancer can
be overwhelming and confusing. Part
1 explains some basics about acute
lymphoblastic leukemia that may help
you better understand this disease.
These basics may also help you start
planning for treatment.
What are blood cells?
Blood is made of many types of cells, called blood
cells. The three main types of blood cells are
platelets, red blood cells, and white blood cells.
Each type of blood cell has a certain job in the body.
Platelets help control bleeding. Red blood cells carry
oxygen throughout the body. White blood cells are
part of the immune system and help fight infections
in the body. The immune system is the body’s natural
defense against infection and disease.
Blood cells are made from immature blood-forming
cells in the bone marrow—the soft, sponge-like tissue
in the center of most bones. See Figure 1.1. These
blood-forming cells are called blood stem cells.
Blood stem cells go through a series of changes as
they grow and develop to make new blood cells.
See Figure 1.2. Blast cells are new, immature blood
cells that grow into mature blood cells over time. A
blood stem cell may become a myeloid stem cell
or a lymphoid stem cell. Myeloid stem cells make
red blood cells, platelets, and a type of white blood
1 About acute
lymphoblastic
leukemia
6 What are blood cells?
8 What is acute lymphoblastic
leukemia?
9 Symptoms of acute lymphoblastic
leukemia
10 Websites | Review

1 About acute lymphoblastic leukemia What are blood cells?
cells called granulocytes. Lymphoid stem cells
make lymphoblasts, which become a type of white
blood cells called lymphocytes. The two main types
of lymphocytes are B-lymphocytes (B-cells) and
T-lymphocytes (T-cells).
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.
Figure 1.2
Blood stem cells make
all types of blood cells
A blood stem cell
can become a
myeloid stem cell
or a lymphoid stem
cell. Blast cells, such
as myeloblasts and
lymphoblasts, are
immature blood cells
that grow into mature
blood cells over time.
Illustration Copyright © 2014 Nucleus Medical Media, All rights reserved. www.nucleusinc.com
Blood stem cell
PlateletsRed blood
cells
B-cell T-cell
Plasma cell
Granulocytes

1 About acute lymphoblastic leukemia What is acute lymphoblastic leukemia?
What is acute lymphoblastic
leukemia?
Leukemia is a cancer that starts in blood-forming
cells in the bone marrow. There is more than one
type of leukemia. Each type of leukemia is named
based on how fast it grows and the type of blood cell
in which it begins. This book focuses on ALL (acute
lymphoblastic leukemia). “Acute” means the leukemia
grows and progresses very fast. “Lymphoblastic”
means it starts in immature white blood cells called
lymphoblasts.
Normally, the amount and type of new blood cells
made is very controlled and balanced. Normal blood
cells grow and divide to make new red blood cells,
white blood cells, and platelets as the body needs
them. When normal blood cells grow old or get
damaged, they die. New blood cells are then made to
replace the old ones. In a person with ALL, too many
lymphoblasts are made.
Every cell contains coded instructions called genes
that tell it what to do in the body. Genes also control
how often a cell divides to make new cells and
how long it lives. Genes are made of a chain of
chemicals called DNA (deoxyribonucleic acid). DNA
is organized into long strands called chromosomes.
See Figure 1.3. An abnormal change in a gene or
chromosome is called a genetic mutation.
ALL begins when a lymphoblast develops a genetic
mutation that causes it to become abnormal and grow
without control. These abnormal lymphoblasts are
called leukemia cells. Leukemia cells make new cells
that aren’t needed and don’t die when they should.
See Figure 1.4.
Leukemia cells don’t develop into mature
lymphocytes the way they should. They don’t help
fight infections in the body. They continue to divide
and copy themselves to make more and more
leukemia cells. The leukemia cells quickly fill up the
bone marrow and crowd out healthy white blood cells,
red blood cells, and platelets that the body needs.
The leukemia cells also spill out of the bone marrow
into the bloodstream. The leukemia cells may spread
to other parts of the body and collect in the spleen,
lymph nodes, liver, testicles, and the area around the
brain and spinal cord.
Figure 1.3
Chromosomes and genes in cells
Genes are sets of coded instructions in
cells for making new cells and controlling
how cells behave. Genes are made of DNA,
which is carried in long strands called
chromosomes. Every cell has 23 pairs of
chromosomes. Each pair is different from
the others and is labeled by a number.
Gene
Chromosomes
Human
cell

1 About acute lymphoblastic leukemia Symptoms of acute lymphoblastic leukemia
Symptoms of acute
lymphoblastic leukemia
A symptom is a health problem a person experiences
that may indicate a disease. ALL can cause a number
of different symptoms. But, some people with ALL
may have few or no symptoms. Symptoms may
result from a shortage of healthy blood cells or from
leukemia cells collecting in certain parts of the body.
Some common symptoms that may be caused by ALL
include:
• Severe tiredness (fatigue),
• Weakness,
• Dizziness,
• Shortness of breath,
• Frequent infections,
• Fever,
• Bruising or bleeding easily,
• Pain in arms, legs, or joints,
• Unusual sweating at night,
• Unexplained weight loss, and
• Feeling of fullness in the belly area beneath
the ribs.
However, these symptoms may be caused by other
health conditions.
Figure 1.4
Normal cell growth versus
leukemia cell growth
Normal cells grow and divide to make
new cells as the body needs them.
Normal cells die when they are old or
damaged. New cells are then made to
replace the old. Leukemia cells don’t
die when they should. Instead, they
continue to grow and divide to make
more and more copies of themselves.

1 About acute lymphoblastic leukemia Websites | Review
Websites
American Cancer Society
www.cancer.org/cancer/leukemia-
acutelymphocyticallinadults/detailedguide/leukemia-acute-
lymphocytic-what-is-all
National Cancer Institute
www.cancer.gov/cancertopics/pdq/treatment/adultALL/
Patient
Leukemia and Lymphoma Society
www.lls.org/diseaseinformation/leukemia/
acutelymphoblasticleukemia/signssymptoms/
Be the Match
www.bethematch.org/For-Patients-and-Families/Learning-
about-your-disease/Acute-Lymphoblastic-Leukemia/
www.bethematch.org/For-Patients-and-Families/Learning-
about-your-disease/Acute-lymphoblastic-leukemia/
Symptoms-of-ALL/
Review
• A blood stem cell is a cell from which all other
types of blood cells are made.
• Blood cells are made in the soft tissue in the
center of most bones called bone marrow.
• Leukemia is a cancer that starts in blood-
forming cells in the bone marrow.
• ALL is a fast-growing type of leukemia in
which too many immature white blood cells
called lymphoblasts are made.
• White blood cells fight disease and infections
in the body.


11
2
Overview of tests

Treatment planning starts with testing.
This section describes the tests that
are used to confirm (diagnose) acute
lymphoblastic leukemia and plan
treatment. This information can help
you use the Treatment guide in Part
6. It may also help you know what to
expect during testing. Not every person
with acute lymphoblastic leukemia will
receive every test listed.
General health tests
Medical history
Before and after cancer treatment, your doctor will
assess your medical history. Your medical history
includes any health events in your life and any
medications you’ve taken. Your doctor will ask
about any symptoms and health conditions that you
have had. This information may affect which cancer
treatment is best for you. It may help to make a list
of old and new medications while at home to bring to
your doctor’s 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.
Your doctor may listen to your lungs, heart, and
intestines. Your doctor may also feel different parts of
your body to see if organs are of normal size, are soft
or hard, or cause pain when touched. For example,
your doctor may feel your belly area (abdomen) to
check for signs of an enlarged liver or spleen. In
males, the testicles will also be examined.
Checking for signs of infection is a key part of the
physical exam. This is often referred to as an infection
2 Overview of tests
12 General health tests
13 Blood tests
14 Bone marrow tests
18 Spinal fluid tests
19 Imaging tests

2 Overview of tests Blood tests
evaluation. Enlarged lymph nodes are an example
of a common sign of infection. Your doctor may feel
certain areas such as your armpits and behind your
jaw to check for enlarged lymph nodes.
Blood tests
Doctors test blood to look for signs of ALL in the
bloodstream (circulating blood). Blood tests are done
along with other initial tests to help confirm ALL.
They are also used to assess if organs are working
well. Blood tests may be repeated to check how well
treatment is working and to check for side effects. For
a blood test, your doctor will insert a needle into a
vein to remove a sample of blood. The blood sample
will then be sent to a lab where a pathologist will
examine it with a microscope. The blood tests used
for ALL are listed in Chart 2.1 and described below.
CBC with differential
A CBC (complete blood count) is a test that
measures the number of white blood cells, red blood
cells, and platelets in a sample of blood. The CBC
should include a differential. The differential measures
the different types of white blood cells in the sample.
A high number of white blood cells and a low number
of red blood cells and platelets may be signs of ALL.
This is because ALL causes too many immature
white blood cells to be made. These white blood cells
may overcrowd the bone marrow so that too few
normal blood cells are made. A CBC with differential
is given along with other initial tests when ALL is first
suspected. This test is also repeated during and after
treatment to check treatment results.
Blood chemistry tests
A blood chemistry test measures the levels of certain
chemicals in a sample of blood. Different organs and
tissues in the body naturally release chemicals into
the blood. Other organs are remove some chemicals
from the blood. Abnormal levels of certain chemicals
in the blood may be a sign that an organ isn’t working
well.
Doctors use blood chemistry tests to assess if certain
organs and body systems are working well. These
tests may be given along with other initial tests when
ALL is first confirmed (diagnosed). They also may be
given during and after ALL treatment. Blood chemistry
tests can help detect organ damage caused by the
leukemia cells or ALL treatments. The different types
of blood chemistry tests that doctors use for ALL are
described below.
Blood chemistry profile
A blood chemistry profile measures a set of several
different chemicals in a sample of blood. This test
is given along with other initial tests for ALL. It gives
information about the general health of your body and
organs.
Liver function tests
The liver is an organ that removes waste from
the blood and helps to digest food. Liver function
Chart 2.1 Blood tests
Test name
CBC (complete blood count) with differential
Blood chemistry profile
Liver function tests
TLS (tumor lysis syndrome) panel
Coagulation tests
Type and screen
HLA (human leukocyte antigen) typing

2 Overview of tests Bone marrow tests
tests measure certain substances that are made
or processed by the liver. Doctors use these tests
to assess if your liver is working well and to check
for damage that may be caused by certain cancer
treatments.
Tumor lysis syndrome panel
TLS (tumor lysis syndrome) is a condition that
occurs when many cancer cells die very quickly due
to treatment. As cancer cells die, they release their
contents into the blood. This can cause very high
levels of certain chemicals in the blood. A TLS panel
measures the levels of these chemicals in the blood.
Uric acid is one of the chemicals released by dying
cancer cells. Very high levels of uric acid and other
chemicals in the blood can be very dangerous. It can
cause serious damage to organs such as the kidneys,
liver, and heart.
Coagulation tests
Coagulation tests are used to assess if blood is able
to clot (coagulate) the way it should. When a person
is cut or injured, platelets and proteins called clotting
factors clump together to form a clot to stop bleeding.
Abnormal levels of platelets or clotting factors can
cause bleeding problems.
Type and screen
Blood is classified into groups based on certain
substances found on the surface of the blood cells.
These groups are called blood types. Type and
screen is test that finds a person’s blood type. Most
patients with ALL will need a transfusion of blood from
another person, called a donor. The donor’s blood
type must be a good match that works well with the
patient’s blood type.
HLA typing
HLAs (human leukocyte antigens) are special
proteins found on the surface of most cells in the
body. These proteins help the body to tell its own
cells apart from foreign cells. The unique set of HLA
proteins on a person’s cells is called the HLA type.
HLA types differ among people just like blood types
differ among people. HLA typing is a blood test that
finds a person’s HLA type. This test must be done
before treatment that transfers blood stem cells from
another person to the patient (See Part 4 on page
33). The patient’s HLA type and the donor’s HLA type
must be a near-perfect match for this treatment to
work. This is because the HLA type affects how the
body responds to foreign substances.
Bone marrow tests
Bone marrow is the soft, sponge-like tissue in the
center of most bones where blood cells are made.
Bone marrow tests are used to confirm (diagnose)
ALL and to check how well treatment is working.
There are many types of bone marrow tests that may
be used for different reasons. The bone marrow tests
used for ALL are listed in Chart 2.2 and described in
the text on the next pages.
Chart 2.2 Bone marrow tests
Test name
Bone marrow biopsy
Bone marrow aspiration
Cell assessment, also called morphologic
examination
Flow cytometry
Cytogenetic testing, also called karyotyping
FISH (fluorescence in situ hybridization)
PCR (polymerase chain reaction)

Bone marrow biopsy and aspiration
To confirm if you have ALL, a sample of bone marrow
must be removed from your body to test for leukemia
cells. The removal of tissue from your body for testing
is called a biopsy. A biopsy is generally a safe test
and can typically be done in about 30 minutes. After
the samples are collected, they are sent to a lab for
testing.
A bone marrow biopsy removes a small piece of solid
bone along with a small amount of soft bone marrow
inside the bone. A bone marrow aspiration removes
a small amount of liquid bone marrow from inside the
bone. Often, both tests are done at the same time on
the back of the hip bone.
These bone marrow tests are done as outpatient
tests—this means you don’t have to spend the night
in the hospital. First, you may be given a sedative
injected with a needle into your vein. Your doctor will
then clean the area of skin where the biopsy will be
performed. Next, you will receive local anesthesia
to numb the area of skin and bone beneath. After
the area is numbed, a hollow needle will be inserted
into your skin and then pushed into the bone to
remove the liquid bone marrow with a syringe. Then,
a wider needle will be inserted into the bone and
rotated to remove the solid bone and marrow sample.
See Figure 2.1. You may feel some pain while the
samples are being removed and your skin may be
bruised afterward.
At the lab
Cell assessment
A pathologist will view the bone marrow sample with a
microscope to assess the physical appearance of the
cells. This lab test is simply called cell assessment.
Doctors may also refer to this test as a morphologic
examination.
Staining the samples with special dyes helps to show
the differences between parts of a single cell and
differences between many cells. The pathologist will
assess the number, size, shape, appearance, type,
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.

and other features of the cells in the bone marrow
sample. This helps to determine if the cells look more
like normal, mature cells or more like abnormal,
immature cells. Cell assessment is an important
test that doctors use to find out the percentage of
immature cells called lymphoblasts in the bone
marrow.
A diagnosis of ALL generally requires that at least 20
percent of cells in the bone marrow are lymphoblasts.
This means that at least 20 out of every 100 cells
in the bone marrow are lymphoblasts. In a healthy
person without ALL, no more than 5 out of every 100
cells in the bone marrow are immature (blast) cells.
Flow cytometry
Flow cytometry looks at certain substances on the
surface of cells to identify the type of cells present.
It can show if cells are normal or abnormal and can
tell the difference between types of leukemia cells.
Doctors use this test to confirm (diagnose) ALL and to
get more details about the leukemia cells. This test is
also repeated to check how well treatment is working.
Flow cytometry is used to find the specific type of
lymphocyte that ALL started in based on the type
and pattern of proteins on the surface of the cells.
This process is called immunophenotyping. Results
of immunophenotyping are important for treatment
planning. (See Part 3 on page 22 for details on
treatment planning.) A sample of bone marrow is
often used for immunophenotyping. But, a blood
sample can also be used.
Doctors also use flow cytometry to measure the
amount of leukemia cells present in a sample of bone
marrow (preferred) or blood. It is a very sensitive
test that can detect leukemia cells that can’t be seen
with a microscope. It can find a single leukemia cell
among 10,000 normal cells. This helps doctors check
if treatment is working well.
Flow cytometry can also measure the amount of DNA
in the leukemia cells. The amount of DNA—called the
DNA index—reflects the number of chromosomes in
the leukemia cells. The DNA index can be measured
in a sample of blood or bone marrow.
Cytogenetic testing
Cytogenetic testing, also called karyotyping, uses
a microscope to examine the chromosomes inside
cells. Chromosomes are long strands of DNA that
contain genes. Genes are sets of coded instructions
for making and controlling cells. In ALL, the leukemia
cells often have abnormal chromosome changes that
can be seen with a microscope.
Doctors use cytogenetic testing to detect abnormal
changes in the chromosomes of leukemia cells.
A “map” of the chromosomes, called a karyotype,
is examined with a microscope by a pathologist.
The pathologist assesses the size, shape, number,
arrangement, and structure of the chromosomes to
look for abnormal changes. This test can also be
used to count the number of leukemia cells.
Many different types of chromosome changes may
occur in ALL. The leukemia cells may have an
abnormal number of chromosomes—too many or too

few. The leukemia cells may also have more than one
type of chromosome change.
Sometimes pieces of chromosomes break off and
switch with each other. This is called a translocation.
The Philadelphia chromosome is an important
example of a translocation that occurs in some people
with ALL. The Philadelphia chromosome is caused by
a translocation between parts of chromosomes 9 and
22. See Figure 2.2. This translocation also forms the
abnormal BCR-ABL fusion gene on the Philadelphia
chromosome. A fusion gene is a new gene that is
formed when parts of two separate genes are joined
(fused) together.
Certain abnormal chromosome changes in the
leukemia cells can affect treatment options and
outlook. Thus, this is an important test that is used to
help plan treatment for ALL.
This test is given along with other initial tests when
ALL is first diagnosed. Cytogenetic testing is often
done on a bone marrow sample at first. But, it can
also be done on a blood sample.
FISH
FISH (fluorescence in situ hybridization) is a very
sensitive lab test that can detect certain abnormal
changes in a cell’s genes or chromosomes. It can
detect most abnormal changes that can be seen with
a microscope. It can also detect some changes that
are too small to be seen with basic cytogenetic testing
(karyotyping).
Doctors use FISH to detect certain abnormal gene and
chromosome changes in leukemia cells. This test uses
special color dyes, called probes, that attach only to
certain genes or parts of certain chromosomes.
For example, the Philadelphia chromosome, which
contains the BCR-ABL fusion gene, is a common
abnormal change found in adults with ALL. To detect
this, FISH uses color probes that attach to the BCR
gene and the ABL gene in chromosomes. The
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 an important chromosome
change that affects which
treatments are best for you.
Chromosome 9
ABL gene
Chromosome 22
BCR
gene
Normal chromosomes Chromosomes break Changed chromosomes
BCR-ABL
gene
Philadelphia
chromosome
Chromosome 9
Chromosome 22
BCR
gene
Chromosome 9
ABL gene

1 Overview of tests Spinal fluid tests
BCR-ABL fusion gene, located on the Philadelphia
chromosome, is shown by the overlapping colors of the
two probes.
Like cytogenetic testing, FISH is used to help plan
treatment for ALL. This test can be performed on a
sample of blood or bone marrow.
PCR
PCR (polymerase chain reaction) is a very sensitive
test that detects abnormal gene and chromosome
changes in cells. It can find genetic mutations that
are too small to be seen with a microscope. Doctors
use this test to detect certain gene and chromosome
changes that are commonly found in ALL. An example
of this is the BCR-ABL fusion gene located on the
Philadelphia chromosome. PCR can detect abnormal
gene changes and measure the number of cells that
have them.
PCR is very helpful for checking how well treatment
is working. When the leukemia cells have certain
genetic changes, PCR can detect and measure
the amount of leukemia cells left. This test is very
sensitive and can detect a single leukemia cell among
more than 10,000 normal cells. PCR can be done on
a sample of bone marrow or blood. Bone marrow is
often preferred, especially to check treatment results.
Spinal fluid tests
A lumbar puncture is a procedure that removes a
sample of the fluid that surrounds the brain and spinal
cord. This fluid is called cerebrospinal fluid or spinal
fluid for short. ALL may spread to the area around the
brain and spinal cord, which form the CNS (central
nervous system).
To know if ALL has spread to this area, doctors must
remove a sample of spinal fluid from your body to test
for leukemia cells. A lumbar puncture, also called a
spinal tap, may be done when ALL is first diagnosed
or at a later time that fits with the treatment plan. A
lumbar puncture may also be used to give liquids
such as drug treatments.
For this procedure, you may be asked to lie on the
exam table on your side with your knees tucked up
near your chest. Or, you may be asked to sit on the
edge of the exam table and lean slightly down and
forward over your knees. See Figure 2.3. First you
will be given local anesthesia to numb the lower part
of your back over your spine. Next, a thin needle will
be inserted between the bones of the spine and into
the area near the spinal cord to collect a fluid sample.
You may feel some pressure during the procedure.
The fluid sample will then be sent to a lab for testing.
Figure 2.3
Lumbar puncture
Doctors perform a lumbar puncture to
remove a sample of spinal fluid to test
for leukemia cells. A lumbar puncture
may also be used to give liquids such
as drug treatments.
Illustration Copyright © 2014 Nucleus Medical Media,
All rights reserved. www.nucleusinc.com

2 Overview of tests Imaging tests
Imaging tests
Imaging tests take pictures of the inside of your body.
Imaging tests are not often used for ALL. However,
they may be useful to look for infections or to check for
signs that ALL has spread to the brain and spinal cord.
Imaging tests are often easy to undergo. Before the
test, you may be asked to stop eating or drinking for
several hours. You also should remove any metal
objects that are on your body. For some imaging
tests, a contrast dye may be injected into your vein to
make the pictures clearer. The types of imaging tests
that may be used for ALL are listed in Chart 2.3 and
described in the text below.
CT scan
A CT (computed tomography) scan takes many
pictures of a body part from different angles using
x-rays. See Figure 2.4. A computer combines all
the pictures to make one clear picture. A CT scan of
your head may be recommended if you have certain
symptoms that suggest ALL might have spread to
your brain and spinal cord. A CT scan of your chest
may be recommended for certain patients to see if
leukemia cells have collected in this area.
MRI scan
An MRI (magnetic resonance imaging) scan 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 may be recommended if you
have certain symptoms that suggest ALL might have
spread to your brain and spinal cord.
Echocardiogram
An echocardiogram is an imaging test that uses
sound waves to make pictures of the heart. This
test is used to check how well your heart is working.
It lets your doctor see how your heart is beating
and pumping blood. Certain drugs that are used to
treat ALL can damage heart tissue. Therefore, your
doctor may want to assess your heart function before
starting ALL treatment. This is especially important if
you’ve had any heart issues in the past. This test may
be repeated during and after ALL treatment to check
for any heart damage that may have occurred.
Figure 2.4 CT scan machine
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.
Chart 2.3 Imaging tests
Test name
CT (computed tomography) scan
MRI (magnetic resonance imaging) scan
Echocardiogram

2 Overview of tests Websites | Review
Websites
www.cancer.org/cancer/leukemia-acutelymphocyticallinadults/
detailedguide/leukemia-acute-lymphocytic-diagnosis
Patient/page1#Keypoint5
Leukemia & Lymphoma Society
acutelymphoblasticleukemia/diagnosis/
Be the Match
www.bethematch.org/For-Patients-and-Families/Finding-a-
donor/HLA-matching/
Review
• Cancer tests are used to plan treatment and
check how well treatment is working.
• To confirm if you have ALL, a sample of bone
marrow must be removed from your body for
testing.
• The removal of tissue from your body for testing
is called a biopsy.
• Blood tests are used to look for signs of disease
and check how well your organs are working.
• Flow cytometry is a sensitive test that identifies
cells by the set on proteins on the cell surface.
This is called immunophenotyping.
• Cytogenetic testing, PCR, and FISH help
doctors detect abnormal chromosome changes
in leukemia cells.


3
Treatment planning

Once ALL is confirmed (diagnosed),
doctors begin the process of planning
treatment. The treatments that doctors
recommend depend on a number of
important factors. Part 3 explains how
doctors plan treatment for ALL and
describes the main factors that affect
treatment options.
Subtypes of ALL
ALL is divided (classified) into smaller groups based
on certain features of the leukemia cells. These
smaller groups are called subtypes. The ALL subtype
is an important factor that doctors use to plan
treatment.
Cell subtypes
Doctors classify ALL into two broad subtypes
based on the type of lymphocyte the leukemia
cells come from. These are called cell subtypes.
Each type of lymphocyte can be identified by the
unique set of proteins on the surface of the cells.
The unique set and pattern of proteins is called the
immunophenotype.
There are many ALL cell subtypes based on
immunophenotype. Some are more common or more
important for treatment planning than others. The two
main cell subtypes based on immunophenotype are
described next.
3 Treatment planning
22 Subtypes of ALL
24 Age issues in ALL
25 What is a prognostic factor?

3 Treatment planning Subtypes of ALL
• B-cell ALL – This subtype of ALL starts
in developing B-lymphoblasts—immature
cells that normally become mature B-cells
(B-lymphocytes). This is the most common
ALL subtype overall. Among adults with ALL,
about 75 out of 100 have B-cell ALL. Among
children with ALL, about 88 out of 100 have
this subtype.
• T-cell ALL – This subtype of ALL starts
in developing T-lymphoblasts—immature
cells that normally become mature T-cells
(T-lymphocytes). This subtype is less common
overall, but occurs more often in adults than in
children. Among adults with ALL, about 25 out
of 100 have T-cell ALL. Among children with
ALL, about 12 out of 100 have this subtype.
Cytogenetic subtypes
Doctors also classify ALL into subtypes based on the
type of abnormal changes found in the chromosomes
of the leukemia cells. Cytogenetics is the study of
chromosomes. Thus, ALL subtypes that are based
on chromosome changes are called cytogenetic
subtypes.
Many different types of chromosome changes may
occur in ALL. The Philadelphia chromosome is an
abnormal chromosome found in the leukemia cells
of some people with ALL. It is formed when pieces
of chromosomes 9 and 22 break off and switch with
each other.
ALL can be classified into many different cytogenetic
subtypes based on chromosome changes. However,
some are more common or more important for
treatment planning than others. The two main
cytogenetic subtypes of ALL that doctors use for
treatment planning are based on the presence or
absence of the Philadelphia chromosome. These
subtypes are described next.
• Ph-positive ALL – In this subtype of ALL,
the leukemia cells contain the abnormal
Philadelphia chromosome. This is the most
common cytogenetic subtype in adults with
ALL. It is rare in children. The chance of
having this cytogenetic subtype increases
with age. Among adults with ALL, about 25
out of 100 have Ph-positive ALL. Among
children with ALL, about 3 out of 100 have this
subtype.
• Ph-negative ALL – In this subtype of ALL, the
leukemia cells do not contain the abnormal
Philadelphia chromosome. This cytogenetic
subtype is more common in children than in
adults. Among adults with ALL, about 75 out
of 100 have Ph-negative ALL. Among children
with ALL, more than 95 out of 100 have this
subtype.

3 Treatment planning Age issues in ALL
Age issues in ALL
A person’s age at the time ALL is diagnosed is one
of the most important factors that doctors use to
plan treatment. As a result, recommendations in the
Treatment guide are divided into two age groups:
• AYAs (adolescent and young adults) –
patients who are 15 to 39 years of age, and
• Older adults – patients who are 40 years of
age or older.
AYAs and older adults differ in many ways. These
differences carry over into personal, social, emotional,
and medical needs. There are also important
differences between AYAs and older adults with ALL
that doctors must consider when making treatment
decisions. In particular, AYAs have much better
outcomes when given more intensive ALL treatments
like those designed for children.
Very intense treatments can cause serious side
effects that get harder to tolerate with age. Because
AYAs are able to tolerate the intensive treatments,
they benefit greatly and have much better treatment
results. The side effects of intensive treatments tend
to be more severe and harder to recover from for
older patients.
Generally, doctors use the age of 65 as the cut-off
for intensive treatments since older patients may not
be able to tolerate them. However, age alone is not
a good gauge for deciding if a person can tolerate
these treatments. A person older than 65 who is in
good health and doesn’t have other serious health
problems may still benefit from more intensive
treatments. Likewise, a person younger than 65
who isn’t in very good health and has other serious
health problems may not be able to tolerate intensive
treatments.
Therefore, doctors must also consider your overall
health in addition to your age. Assessing your overall
health, fitness, and other current health problems is
especially important. This includes assessing how
well organs such as your heart, lungs, liver, and
kidneys are working.
AYAs have a unique set of needs and
challenges that differ greatly from
those of young children and older
adults.
Discussing all of these important aspects is
beyond the scope of this book. More details and
information focused on AYAs with cancer can
be found in the NCCN Guidelines for Patients®
:
Caring for Adolescents and Young Adults. These
guidelines are available for free at
www.nccn.org/patients.

3 Treatment planning What is a prognostic factor?
What is a prognostic factor?
Several important factors affect treatment options
and the likely outcome (prognosis) of ALL. Something
that affects and helps predict prognosis is called a
prognostic factor.
Doctors use certain prognostic factors to help predict
how ALL will likely progress and respond to treatment.
This helps doctors plan how intensive treatment
needs to be for each patient to kill all the leukemia
cells and keep them from coming back. These factors
can also help doctors decide which type of treatment
will likely work best.
Prognostic factors that are linked with a lower chance
(risk) that ALL will come back after treatment are
called “good risk” features. Factors linked with a
higher risk that ALL will come back are called “poor
risk” features. Doctors give more intensive treatments
for ALL that has poor risk features. The presence of
poor risk features does not mean ALL can’t be cured.
A number of different factors can affect prognosis in
ALL. However, some are more important for treatment
planning than others. The main factors doctors use
to guide treatment planning are your age and the
cytogenetic subtype. Prognostic factors for ALL are
described below.
Age. The leukemia cells in older patients tend to be
more resistant to treatment. Stronger treatments may
be needed to kill all the leukemia cells and keep them
from coming back.
Philadelphia chromosome. Leukemia cells that
have the Philadelphia chromosome can be harder to
treat. But, new treatments have improved outcomes
in the past few years.
Chromosome changes. Certain changes in
chromosomes can make leukemia cells harder to
treat. This includes having fewer than the normal
number of chromosomes and having five or more
chromosome changes.
White blood cell count. The number of white
blood cells in the blood at the time ALL is confirmed
(diagnosed) can also affect prognosis. Having a very
high white blood cell count at diagnosis is considered
a poor risk feature in children with ALL. This factor
has a much smaller effect on treatment planning for
adults with ALL.

3 Treatment planning Websites | Review
 Websites
lymphocytic-classified
Patient#Keypoint6
acutelymphoblasticleukemia/allsubtypes/
acutelymphoblasticleukemia/beforetreatment/
Review
• Once ALL is confirmed (diagnosed), doctors
plan treatment based on certain test results.
• A number of important factors guide treatment
decisions and the likely outcome.
• Age is one of the most important factors that
affect treatment options.
• A prognostic factor is something that
affects and helps predict the likely outcome
(prognosis).
• Doctors classify ALL into smaller groups
called subtypes based on certain features of
the leukemia cells.

27
4
Overview of cancer treatments

4 Overview of cancer
treatments
28 Order of treatments
30 Chemotherapy
32 Targeted therapy
33 Stem cell transplant
34 Radiation therapy
35 Clinical trials
The treatment of ALL is very complex
and requires a multidisciplinary team of
experts. There are many different types
of treatments for ALL. Which treatment
you will receive depends on a number
of factors such as your age, general
health, the ALL cell subtype, and the
cytogenetic subtype. The main types
of treatments for ALL are described on
the next pages. This information may
help you use the Treatment guide in
Part 6. It may also help you know what
to expect during treatment. Not every
person with ALL will receive every
treatment listed.
Order of treatments
The treatment of ALL is a long-term process that lasts
about two to three years. ALL treatment is divided
into three main steps, called phases. The length of
each phase may vary depending on the intensity of
the treatments and other factors. The phases of ALL
treatment are described below.
Induction
The first phase of ALL treatment is called induction.
This phase may also be called by other names such
as remission induction, or induction therapy. The
goal of induction therapy is to kill as many leukemia
cells in the bone marrow as possible. It is meant to
cause (induce) a remission. A remission is when no
leukemia cells can be seen in blood or bone marrow
examined with a microscope and blood counts are
back to normal. The induction phase generally lasts
about four weeks (one month). You will likely need to
stay in the hospital for some or most of this time.

4 Overview of cancer treatments Order of treatments
CNS prevention and treatment
CNS (central nervous system) prevention and
treatment is started during induction and given
throughout all phases of ALL treatment. This part of
treatment may also be called by other names such as
CNS prophylaxis. CNS-directed therapy is given to
keep ALL from spreading to the area around the brain
and spinal cord. When leukemia cells are found in this
area, it is called CNS disease.
Consolidation
The second phase of ALL treatment is called
consolidation. This phase may also be called by
other names such as intensification or postremission
consolidation. Consolidation therapy is given once
ALL is in remission. The goal of consolidation therapy
is to kill any leukemia cells that may still be in your
body. During the consolidation phase, treatments
are intensified and given in higher doses than during
induction. The consolidation phase often lasts for a
few months.
Maintenance
The third phase of ALL treatment is called
maintenance. The goal of maintenance therapy
is to prevent ALL from coming back. Maintenance
generally consists of lower doses of drugs given
over an extended period of time. The lower
doses tend to have less severe side effects. The
maintenance phase lasts about two to three years.
Consolidation and maintenance are often jointly
called postremission therapy. Postremission therapy
refers to any treatments given after ALL is in complete
remission.
Treatment response
A treatment response is an outcome or
improvement related to treatment. Doctors first
assess for a treatment response at the end of
induction therapy. To check how well treatment
worked, your doctor will examine a sample of
blood and bone marrow with a microscope.
The goal of ALL treatment is to result
in a complete remission.
After reaching a complete remission, a small
amount of leukemia cells may still be in your body
even if they aren’t 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.
Further treatment after a complete remission—
called postremission therapy—is needed to
make sure every last leukemia cell is destroyed.
Postremission therapy is also needed to keep the
leukemia cells from coming back after a complete
remission. A relapse is when ALL comes back after
a complete remission. Sometimes the leukemia
cells don’t respond to induction therapy. ALL that is
not in complete remission after induction is called
refractory ALL.
A complete remission is when:
ü No leukemia cells are seen in the
bone marrow,
ü No more than 5 out of 100 cells in the
bone marrow are blast cells,
ü No blast cells are in the bloodstream,
ü All blood cell counts are back to normal,
and
ü All signs and symptoms of ALL are
gone.

Chemotherapy
The main treatment for ALL involves the long-term
use of chemotherapy. Chemotherapy is the use
of drugs to kill cancer. Many people refer to this
treatment as “chemo.” Chemotherapy drugs travel in
the bloodstream to kill fast-growing cells throughout
the body. Cancer cells grow fast, so chemotherapy
works well to kill cancer cells and stop new ones
from being made. Chemotherapy can also affect
normal cells.
Different types of chemotherapy drugs attack
leukemia cells in different ways. Therefore, more than
one drug is often used. When only one drug is used,
it’s called a single agent. A combination regimen is
the use of two or more chemotherapy drugs. This
may also be referred to as multiagent chemotherapy.
Chemotherapy is given in cycles. A cycle includes
days of treatment followed by days of rest. Giving
chemotherapy in cycles gives the body a chance to
recover before the next treatment. The cycles vary
in length depending on which drugs are used. The
number of cycles given also varies depending on the
regimen used.
A regimen is a treatment plan that specifies the
drug(s), dose, and schedule for a course of treatment.
A chemotherapy regimen consists of a set number of
cycles given over a set amount of time. You may be
given one drug at a time or combinations of different
drugs at the same time. Treatment for ALL often uses
4- or 5-drug combination regimens. Some of the most
common chemotherapy drugs used for ALL are listed
in Chart 4.1.
Corticosteroids, also simply called steroids, are often
given along with chemotherapy drugs to treat ALL.
Corticosteroids are a type of drug used to relieve
swelling and inflammation. But, some corticosteroids
also have anti-cancer effects. Corticosteroids often
used in ALL regimens include prednisone and
dexamethasone.
4 Overview of cancer treatments Chemotherapy
Chart 4.1 Common chemotherapy drugs for ALL
Generic name
Brand name
(sold as)
6-MP (6-mercaptopurine) Purinethol
Asparaginase erwinia
chrysanthemi
Erwinaze
Clofarabine Clolar, Clofarex
Cyclophosphamide Cytoxan
Cytarabine Cytosar-U
Daunorubicin, or daunomycin Cerubidine
Dexamethasone --
Doxorubicin Adriamycin
Etoposide VP-16, VePesid
Idarubicin Idamycin
Ifosfamide Ifex
Methotrexate Folex, Mexate
Nelarabine Arranon
Pegaspargase Oncaspar
Prednisone --
Vincristine Oncovin
VSL (vincristine sulfate
liposome)
Marqibo

4 Overview of cancer treatments Chemotherapy
How chemotherapy drugs are given
Chemotherapy drugs may be given as a pill that
you swallow or as a liquid that is injected into your
body with a needle. It may be injected into a vein,
muscle, or under your skin. When given this way,
the drugs travel in your bloodstream to kill leukemia
cells in all parts of your body. This is called systemic
chemotherapy. An IV (intravenous) infusion is a slow
injection into a vein. An intramuscular injection is
when drugs are given into a muscle. A subcutaneous
injection is when drugs are given under the skin.
Often, doctors give IV chemotherapy through a thin,
soft tube called a central venous line or catheter. One
end of the central line will be inserted into a large
vein in your chest or arm. The other end of the tube
will stay outside of your body. This way, doctors can
give IV chemotherapy treatments frequently without
“sticking” you with a needle every time. Doctors can
also use the central line to give other medicines and
take blood samples. A central line can be left in place
under your skin for weeks or months.
Leukemia cells can also spread to the brain and
spinal cord, called CNS disease. Chemotherapy
that is injected into a vein usually cannot reach
this area. Instead, chemotherapy drugs must be
injected directly into the spinal fluid. This is called IT
(intrathecal) chemotherapy. IT chemotherapy is often
given during a lumbar puncture. IT chemotherapy is
used to treat and prevent CNS disease and relapse.
Chemotherapy regimens for AYAs
and older adults
A protocol is a detailed outline or plan of a medical
treatment, study, or procedure. It describes which
treatments a patient will get and when each treatment
should be given. A treatment protocol covers all phases
of ALL treatment. It states which drugs and regimens
will be used during each phase. A protocol often
includes many chemotherapy regimens that are given
at different times over the course of ALL treatment.
Treatments designed for children with ALL are called
pediatric protocols. The chemotherapy regimens
used for children are often called pediatric regimens.
Likewise, treatments designed for older adults with
ALL are called adult protocols and adult regimens.
Many of the same drugs are used for children and
older adults with ALL. But, the doses and schedules
are different. Importantly, studies show that AYAs—
patients aged 15 to 39—have much better outcomes
when treated more like children. Experts recommend
that treatment for AYAs should be based on pediatric
protocols. This is referred to as a pediatric-inspired
protocol. The main differences between pediatric and
adult treatments are described below.
Pediatric regimens are more intense and complex
than those given to older adults. They use very high
(intensified) doses of certain chemotherapy drugs
that can be hard for older adults to tolerate. Pediatric
regimens tend to use more pegaspargase, vincristine,
and corticosteroids such as dexamethasone and
prednisone. Overall, the doses of these drugs are
much higher than what is given to adults. Some
patients may develop an allergy to pegaspargase. If
this happens, asparaginase erwinia chrysanthemi may
be given instead.
In contrast, adult regimens tend to use more
cyclophosphamide and anthracyclines such as
doxorubicin and daunomycin. These drugs lower
(suppress) the bone marrow’s ability to make
new blood cells. Thus, they are often called
myelosuppressive drugs. Adult regimens also use
allogeneic SCT (stem cell transplant) more often.
(See page 33 for details on this type of treatment.)
Increased (intensified) doses of drugs are given
at certain points during treatment for children and
adults. But, pediatric protocols give intensified doses
more frequently throughout the course of treatment.
In contrast, adult regimens tend to be less intense.

The types and doses of drugs used in adult regimens
are meant to be tolerable for people across a wide
age range. AYAs treated with these regimens may be
under-dosed.
In pediatric protocols, treatment is given for a longer
period of time overall. CNS preventive treatment
is started earlier and given longer. Children often
receive maintenance therapy for about three years.
Adult regimens tend to give maintenance for about
two years.
Targeted therapy
Targeted therapy is treatment with drugs that target
a specific or unique feature of cancer cells. Because
these drugs specifically target cancer cells, they may
be less likely to harm normal cells throughout your
body. The two main types of targeted therapy drugs
used for ALL are described next.
Tyrosine kinase inhibitors
TKI (tyrosine kinase inhibitor) therapy is a type of
targeted therapy. TKIs are used for a subtype of ALL
in which the leukemia cells have the Philadelphia
chromosome. This subtype is called Ph-positive ALL.
The Philadelphia chromosome contains the abnormal
BCR-ABL fusion gene.
The BCR-ABL gene makes an abnormal protein—
called the BCR-ABL protein—that helps leukemia
cells grow. It is a type of protein called a tyrosine
kinase. TKIs block (inhibit) the BCR-ABL protein from
sending the signals that cause too many leukemia
cells to form. The TKI therapy drugs used to treat
ALL are listed in Chart 4.2. These drugs are made
in the form of a pill that is swallowed. TKIs are not
used alone to treat ALL. Instead, a TKI is added to a
4 Overview of cancer treatments Targeted therapy
Chart 4.2 TKI therapy for ALL
Generic name Brand name (sold as)
Bosutinib Bosulif
Dasatinib Sprycel
Imatinib Gleevec
Nilotinib Tasigna
Ponatinib Iclusig

4 Overview of cancer treatments Stem cell transplant
combination chemotherapy regimen. The outcome for
patients with Ph-positive ALL has improved greatly
with TKIs added to the treatment regimen.
TKI drug resistance
A treatment response is an outcome or improvement
related to treatment. Drug resistance is when ALL
doesn’t respond to a drug. Primary resistance is when
ALL doesn’t respond at all to a drug taken for the first
time. This type of resistance is rare in ALL. Secondary
resistance is when ALL responds to a drug at first
and then stops responding after a period of time.
Secondary resistance occurs more often in patients
with ALL and there are a number of possible causes.
Most often, secondary resistance is caused by
changes (mutations) in the part of the BCR-ABL gene
that makes the BCR-ABL protein. These mutations
change the shape of the BCR-ABL protein so that
certain TKIs can’t bind to it effectively. This can cause
the TKI to stop working. But, each TKI drug works
in a slightly different way. One TKI drug may be
able to overcome a mutation that another TKI can’t.
Therefore, switching to a different TKI may result in
a treatment response after ALL stops responding or
becomes resistant to a prior TKI.
Monoclonal antibodies
Monoclonal antibodies are another type of targeted
therapy used for ALL. A monoclonal antibody is a
type of immune system protein that is made in a lab.
Monoclonal antibodies are designed to attach to a
certain target or substance found on the surface of
cancer cells. Most monoclonal antibodies can attach
(bind) to only one substance.
Rituximab is a monoclonal antibody that may be used
to treat certain patients with B-cell ALL. Rituximab
targets a protein called CD20 antigen. This protein
is found on the surface of normal and abnormal
B-cells. About half of adults with B-cell ALL have
leukemia cells that express the CD20 antigen. When
rituximab binds to the CD20 antigen, it sends a signal
to the cell to die. Rituximab also marks the cells for
destruction by the immune system. This triggers an
immune response and brings in other immune cells
to attack and kill the “marked” cells. Rituximab is
not used alone to treat ALL. Instead, it is added to a
combination chemotherapy regimen. It is given as a
liquid that is injected into a vein.
Blinatumomab is a special kind of monoclonal
antibody that can bind to two proteins at the same
time. It binds to a protein called CD19 that is found
on immature B-cells and some leukemia cells. It also
binds to a protein called CD3 that is found on T-cells.
T-cells are part of the body’s immune system. By
binding to these two proteins, blinatumomab links the
T-cells to the leukemia cells. This helps the immune
system to find and attack the leukemia cells.
Approved in December 2014, blinatumomab is the
newest treatment for ALL. It may be used for certain
patients with B-cell ALL after other treatments didn’t
work well. It is given as a liquid that is slowly injected
into a vein.
Stem cell transplant
High-dose chemotherapy followed by an SCT may
be a treatment option for some patients with ALL. For
this treatment, high-dose chemotherapy is given first
to destroy normal cells and leukemia cells in your
bone marrow. An SCT is a medical procedure that
replaces the destroyed cells in your bone marrow with
new, healthy blood stem cells.
For the treatment of ALL, the blood stem cells are
collected from another person, called a donor. This
is called an allogeneic SCT. Before the transplant,
special testing must be done to make sure the donor
is a good match for you. HLA typing is a test that is

4 Overview of cancer treatments Radiation therapy
used to find a person’s tissue type, called an HLA
type. (See page 14 for more details on HLA typing.)
An allogeneic SCT creates a new immune system for
your body. This transplant also causes the GVL (graft-
versus-leukemia) effect. The GVL effect is when the
transplanted stem cells (the graft) see the leukemia
cells in your body as foreign and attack them.
High-dose chemotherapy is given before the
transplant to destroy any remaining leukemia cells in
your bone marrow. The high-dose chemotherapy also
destroys normal blood cells in your bone marrow. This
greatly weakens your immune system so that your
body doesn’t attack the transplanted stem cells. Once
the high-dose chemotherapy is complete, the donated
stem cells are put into your body with a transfusion. A
transfusion is when you receive whole blood or parts
of blood put directly into your bloodstream through a
vein. This process can take 1 to 5 hours to complete.
The transplanted stem cells then travel to your bone
marrow and grow to make new healthy blood cells.
This is called engraftment and it usually occurs about
2 to 4 weeks after the transplant. Until then you will
have little or no immune defense, and so you are at
high risk for infection and bleeding. Therefore, you will
likely need to stay in a hospital in a very clean (sterile)
unit for about 2 weeks. It may take a few weeks or
months for blood cells to fully recover so that your
immune system is back to normal.
Considering allogeneic SCT
An allogeneic SCT is a complex treatment and can
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.
Your doctor will consider many important factors
when deciding if an allogeneic SCT is a good choice
for you. These factors include your age and general
health, certain prognostic factors, how well other
treatments worked, and whether a well-matched
donor is available.
An allogeneic SCT is not used as the first or
main treatment for ALL. It may be used as part of
consolidation therapy for certain patients with Ph-
positive ALL or other poor risk features. Doctors may
also consider an allogeneic SCT if prior treatments
fail to kill all of the leukemia cells or keep them away.
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).
Radiation therapy is not usually part of the main
treatment for ALL. But, it may be used to treat
leukemia cells that have spread to the area around
the brain and spinal cord—called CNS disease. To
treat CNS disease, radiation therapy is aimed at the
brain. Doctors may refer to this as cranial irradiation.
Radiation therapy may also be used to treat leukemia
cells that have spread to the testicles.
During treatment, you will lie down on a treatment
table and stay very still. You will be alone while a
technician operates the EBRT machine from a nearby
room. The technician will be able to see, hear, and
speak with you at all times. As treatment is given, you
may hear noises. A session can take between 15 and
30 minutes. Radiation therapy is often given 5 days a
week for several weeks.

4 Overview of cancer treatments Clinical trials
Clinical trials
New tests and treatments aren’t offered to patients as
soon as they’re 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. Clinical trials study how safe and helpful
tests and treatments are. When found to be safe
and helpful, they may become tomorrow’s standard
of care. Because of clinical trials, the tests and
treatments in this book are now widely used to help
patients.
Clinical trials are an important treatment option
for people with ALL. Doctors are still studying
what treatments work best for ALL. NCCN experts
recommend that all patients with ALL receive
treatment on a clinical trial if possible. Receiving
treatment on a clinical trial has been shown to
improve outcomes.
Clinical trials are done in a series of steps, called
phases. This is to fully study how safe and helpful a
test or treatment is for patients. The four phases of
clinical trials are described next using the example of
a new drug treatment:
Phase I trials aim to find the best dose and way to
give a new drug with the fewest side effects. If a drug
is found to be safe, it will be studied in a phase II trial.
Phase II trials assess if a drug works for a specific
type of cancer. They are done in larger groups of
patients with the same type of cancer.
Phase III trials compare a new drug to the standard
treatment. These are randomized, meaning patients
are put in a treatment group by chance.
Phase IV trials test new drugs approved by the
FDA (U.S. Food and Drug Administration) to learn
about short-term side effects, long-term side effects,
and safety. They involve many patients with different
types of cancer.
Joining a clinical trial has benefits. First, you’ll have
access to the most current cancer care. Second, you
will receive the best management of care. Third, the
results of your treatment—both good and bad—will be
carefully tracked. Fourth, you may help other patients
with cancer.
Ask your treatment team if there is an open clinical
trial that you can join. To join a clinical trial, you
must meet the conditions of the study. Patients in
a clinical trial often have a similar cancer type and
general health. This helps ensure that any response
is because of the treatment and not because of
differences between patients. You also must review
and sign a paper called an informed consent form to
join a clinical trial. This form describes the study in
detail, including the risks and benefits.

Websites
lymphocytic-treating-general-info
Patient/page4
www.cancer.gov/cancertopics/factsheet/Therapy/bone-
marrow-transplant
acutelymphoblasticleukemia/treatment/
The Bone Marrow Foundation
www.bonemarrow.org/
Review
• Treatment for ALL is given in steps,
called phases: induction, consolidation or
intensification, and maintenance.
• CNS-directed therapy is given during all
phases of treatment.
• The main treatment of ALL involves long-term
use of chemotherapy.
• Chemotherapy is treatment with drugs that kill
fast-growing cells, including leukemia cells and
normal cells.
• Targeted therapy drugs specifically target
cancer cells.
• A stem cell transplant replaces damaged or
diseased bone marrow with healthy blood
stem cells.
• A clinical trial studies a test or treatment to see
how safe it is and how well it works.
• Treatment for AYA patients should be based on
regimens designed for children.

4 Overview of cancer treatments Websites | Review

37
5
Side effects and supportive care

Supportive care is treatment given to
relieve the health problems caused
by cancer and side effects of cancer
treatment. A side effect is an unhealthy
or unpleasant physical or emotional
condition caused by treatment. Part 5
describes common side effects of ALL
treatments along with recommended
supportive care. Managing symptoms
and side effects with supportive care
is important for your quality of life and
treatment outcome.
Side effects of cancer
treatments
Side effects are new or worse physical or emotional
conditions caused by treatment. Each treatment for
ALL can cause side effects, but how your body will
respond can’t be fully known. You may have different
side effects than someone else.
Controlling side effects is important for your quality
of life. There are many ways to limit these problems.
However, listing all the ways is beyond the scope
of this book. In general, changes in behavior, diet,
or medications may help. Don’t wait to tell your
treatment team about side effects. If you don’t tell
your treatment team, they may not know how you are
feeling. Common side effects of ALL treatments are
listed below.
Chemotherapy. Side effects of chemotherapy
depend on the drug, the dose, how it is given, the
length of treatment, and the person. In general, side
effects are caused by the death of fast-growing cells.
These cells are found in the mouth, intestines, hair
5 Side effects and
supportive care
38 Side effects of cancer treatments
40 Nausea and vomiting
40 Low blood cell counts
41 Infection risks
41 Tumor lysis syndrome

follicles, and bone marrow. Certain chemotherapy
drugs can also cause damage to organs such as the
heart, liver, kidneys, brain, and testicles. Some of the
most common side effects of chemotherapy drugs
may include:
• Nausea and vomiting,
• Numbness in the hands and feet,
• Hair loss,
• Mouth sores,
• Low blood cell counts,
• Fatigue,
• Increased risk of infections,
• Bruising or bleeding easily,
• Problems with blood clotting,
• Not feeling hungry,
• Diarrhea,
• Allergic reactions, and
• Abnormal levels of chemicals in the blood.
Targeted therapy. Like chemotherapy, the side
effects of targeted therapy depend on many factors
including the drug and the dose given. Some of the
side effects listed are caused by only one targeted
drug. Others are caused by many targeted drugs
but differ in how likely they are to occur. Some of the
most common side effects of targeted drugs used for
ALL include:
• Nausea and vomiting,
• Diarrhea,
• Constipation,
• Muscle cramps,
• Fatigue,
• Skin rash,
• Fever,
• Headache, and
• Swelling due to fluid buildup.
Radiation therapy. Side effects of radiation
therapy depend on the dose and the area of your
body being treated. Most of the side effects go away
soon after treatment ends. Some of the most common
side effects of radiation therapy include:
• Skin changes,
• Hair loss,
• Fatigue,
• Upset stomach, and
• Diarrhea.
Allogeneic SCT. Side effects can occur at each
step of treatment with an allogeneic SCT. You will
likely feel tired and weak shortly after the SCT while
waiting for the new blood stem cells to grow in the
bone marrow. During this time you are at increased
risk for infection. Allogeneic SCTs also have a very
high risk of GVHD (graft-versus-host disease). GVHD
is when the donated cells (the graft) see the cells
in your body (the host) as foreign and attack them.
The parts of the body most commonly damaged by
GVHD include the skin, liver, and intestines. GVHD is
a serious side effect that can cause the transplant to
fail by stopping the donated stem cells from growing
in your bone marrow. GVHD can develop within a few
weeks after the transplant or much later. Your doctor
will likely give you medications that lessen (suppress)
the immune system to try to prevent this side effect.

5 Side effects and supportive care Side effects of cancer treatments

5 Side effects and supportive care Nausea and vomiting | Low blood cell counts
Nausea and vomiting
Many chemotherapy drugs can cause nausea and
vomiting. However, medication can be given to lessen
or prevent this side effect. Drugs that prevent nausea
and vomiting are called antiemetics. Antiemetics
should be given before starting chemotherapy
treatment.
Low blood cell counts
ALL and its treatment can cause low blood cell
counts. Very low blood cell counts can cause a
number of health problems. But, there are many ways
to manage this side effect.
A low number of red blood cells can cause fatigue
and shortness of breath. If your red blood cell count
is low, you may be given a transfusion of red blood
cells. A low number of platelets can cause you to
bleed or bruise easily. A transfusion of platelets may
be given if your platelet count is very low.
Having a low number of white blood cells is also very
common during treatment for ALL. But, transfusions
are not used to treat low white blood cell counts.
Instead, you may be given a type of drug called a
growth factor. Growth factors help the bone marrow
to make new healthy white blood cells. This helps to
increase the white blood cell count quickly. Examples
of growth factors include filgrastim and pegfilgrastim.
Growth factors are recommended during parts of ALL
treatment that lower (suppress) the bone marrow’s
ability to make new blood cells.

5 Side effects and supportive care Infection risks | Tumor lysis syndrome
Infection risks
ALL and its treatment can cause very low white
blood cell counts. White blood cells are part of the
immune system and help fight off infection and
disease. Having a very low white blood cell count
puts you at risk for infections. Medications may be
given to prevent or treat different types of infections.
Antibiotics can prevent or treat infections caused
by bacteria. An antifungal is medication for infection
caused by fungus. An antiviral is medication for
infection caused by a virus. Your doctor may also
recommend that you get vaccines for pneumonia and
the flu.
Tumor lysis syndrome
TLS (tumor lysis syndrome) is a condition that occurs
when many cancer cells die very quickly due to
treatment. Chemotherapy destroys a large number
of leukemia cells very quickly. As the cells die, they
breakdown and release their contents into the blood.
This changes the normal balance of chemicals in
the blood. It can cause very high levels of certain
chemicals. Uric acid is one of the chemicals released
by dying cancer cells. Very high levels of uric acid
and other chemicals can be very bad for the body.
It can cause serious damage to organs such as the
kidneys, liver, and lungs. Drugs such as allopurinol
and rasburicase may be given to prevent or lessen
the effects of TLS.

5 Side effects and supportive care Websites | Review
Websites
lymphocytic-treating-chemotherapy
lymphocytic-treating-radiation-therapy
acutelymphoblasticleukemia/treatment/sideeffects/
Cancer.Net
www.cancer.net/cancer-types/leukemia-acute-lymphocytic-
all/coping-side-effects
Be The Match
www.bethematch.org/For-Patients-and-Families/Life-after-
transplant/Graft-versus-host-disease--GVHD-/
Review
• Side effects are new or worse physical or
emotional conditions caused by treatment.
• Supportive care is treatment given to relieve
the symptoms of cancer and side effects of
cancer treatment.
• Supportive care is an important part of ALL
treatment.
• Transfusions may be given for low blood cell
counts.
• Medication can be given to prevent many side
effects.


43
6
Treatment guide

6 Treatment guide
46 6.1 Initial testing for ALL
Presents the first set of tests that are recommended to
confirm (diagnose) ALL and plan treatment.
48 6.2 AYAs with Ph-negative ALL
Presents the treatments that are recommended for
AYAs when the leukemia cells do not contain the
Philadelphia chromosome.
52 6.3 Older adults with Ph-negative ALL
older adults when the leukemia cells do not contain the
56 6.4 AYAs with Ph-positive ALL
AYAs when the leukemia cells contain the abnormal
60 6.5 Older adults with Ph-positive ALL
older adults when the leukemia cells contain the
abnormal Philadelphia chromosome.
64 6.6 Follow-up after treatment for ALL
Presents the tests and schedule of follow-up that is
recommended after completing treatment for ALL.
66 6.7 Relapsed and refractory
Ph-negative ALL
patients with Ph-negative ALL that didn’t respond to
treatment or came back after a complete remission.
68 6.8 Relapsed and refractory
Ph-positive ALL
patients with Ph-positive ALL that didn’t respond to
treatment or came back after a complete remission.

NCCN experts recommend that
all patients receive treatment in
a specialized cancer center with
expertise and experience in ALL.
It’s important to be cared for by a multidisciplinary
team of experts with experience in treating patients
your age. Access to clinical trials is also a chief
priority. Specialized cancer centers, such as large
academic centers, have the experts, experience, and
research to provide the best care for patients with
ALL.
Part 6 is a guide through the treatment options for
patients with ALL. It shows which tests and treatments
are recommended under which conditions. This
information is taken from the treatment guidelines
written by NCCN experts for ALL doctors.
The treatment recommendations in this guide are
grouped based on patient age and presence of the
Philadelphia chromosome. The AYA (adolescent and
young adult) group includes patients who are 15 to 39
years of age. The older adult group includes patients
who are 40 years of age or older. The main factors
that affect treatment planning and recommendations
are described in Part 3 on page 22.
Much effort has been made to make this guide easy
to read. Charts list the treatment options and map the
steps through the treatment process. The text along
with each chart explains the information shown in the
chart. Some words that you may not know are defined
on the page or in the Dictionary on page 84. More
information about the tests and treatments in this
guide can be found in Parts 2 through 5.
6 Treatment guide Acute lymphoblastic leukemia

6.1 Initial testing for ALL
Chart 6.1 shows the initial tests that are
recommended when your doctor thinks you may have
ALL. These tests are used to confirm (diagnose) ALL,
assess for symptoms and prognostic factors, and plan
treatment. For full details on each test, see Part 2 on
page 12.
Initial tests
To confirm if you have ALL, a sample of bone marrow
must be removed from your body to test for leukemia
cells. A bone marrow biopsy removes a small piece
of solid bone along with a small amount of soft bone
marrow inside the bone. A bone marrow aspiration
removes a small amount of liquid bone marrow
from inside the bone. The samples will be sent to
a lab where a pathologist will examine them with a
microscope.
The pathologist will perform a number of lab tests
on the bone marrow samples. Cell assessment and
flow cytometry are used to find out how many cells in
the bone marrow are lymphoblasts. ALL is confirmed
when at least 20 out of every 100 cells in the bone
marrow are lymphoblasts.
Flow cytometry looks at the set of proteins on
the surface of cells to identify the type of cells
present. This process is called immunophenotyping.
Doctors use this test to find out the type of
lymphocyte ALL started in. Based on the results of
immunophenotyping, ALL is classified into two main
cell subtypes: B-cell ALL and T-cell ALL.
Cytogenetic testing, also called karyotyping, is used
to find abnormal changes in the chromosomes of the
leukemia cells. Importantly, doctors use this test to
assess for the abnormal Philadelphia chromosome.
6 Treatment guide Initial testing for ALL
Initial tests Next tests
Bone marrow biopsy and bone
marrow aspiration for:
• Cell assessment,
• Flow cytometry,
• Cytogenetic testing,
• FISH, and
• PCR
Chart 6.1 Tests for diagnosis and treatment planning
• Medical history and physical exam,
• Testicular exam (for males),
• Infection evaluation,
• CBC with differential,
• Blood chemistry profile,
• Liver function tests,
• TLS panel,
• Coagulation tests,
• HLA typing,
• Lumbar puncture ,
• Possible CT or MRI of the head,
• Possible CT of the chest, and
• Possible echocardiogram

Based on the results of this test, ALL is classified
into two main cytogenetic subtypes: Ph-negative
ALL and Ph-positive ALL. Ph-negative ALL means
the leukemia cells do not have the Philadelphia
chromosome. Ph-positive ALL means the leukemia
cells contain the Philadelphia chromosome. FISH and
PCR also detect abnormal gene and chromosome
changes in the leukemia cells. These tests are very
sensitive and can detect abnormal changes that can’t
be seen with a microscope.
Next tests
The medical history and physical exam give your
doctor an idea about your general health. During the
physical exam, your doctor may feel your belly area
to check for signs of an enlarged liver or spleen. In
males the testicles will also be examined. Checking
for signs of infection is also a key part of the physical
exam. Your doctor may feel certain areas of your
body for enlarged lymph nodes, which is a common
sign of infection.
A CBC with differential will show if blood cell counts
are abnormal. A high number of white blood cells and
a low number of red blood cells and platelets may
be signs of ALL. A blood chemistry profile measures
chemicals in the blood to assess if organs are
working well. Liver function tests check if your liver
is working well. A TLS panel checks for high levels of
uric acid and other chemicals that may damage your
kidneys. Coagulation tests show if your blood is able
to clot well to control bleeding. HLA typing finds your
tissue type, called an HLA type. This test is used to
find a donor for an allogeneic SCT.
A lumbar puncture removes a sample of spinal fluid
to check if leukemia cells have spread to the brain
and spinal cord—called CNS disease. A lumbar
puncture can also be used to inject drugs directly into
the spinal fluid to prevent or treat CNS disease. Your
doctor may want to do a CT or MRI scan of your head
if you have certain symptoms that may be caused by
CNS disease. For T-cell ALL, your doctor will likely
also do a CT scan of your chest.
An echocardiogram is an imaging test that shows
how well your heart is working. Some chemotherapy
drugs can cause serious damage to your heart. Thus,
your doctor may want to check the health of your
heart before starting ALL treatment. This is especially
important if you’ve had any heart problems in the
past.
Your doctors will use the results of all these tests to
create the best treatment plan for you.
Next steps: 
For Ph-negative ALL: If you are 15 to
39 years old, see Part 6.2 for treatment
recommendations. If you are 40
years of age or older, see Part 6.3 for
treatment recommendations.
For Ph-positive ALL: If you are 15 to
39 years old, see Part 6.4 for treatment
recommendations. If you are 40
years of age or older, see Part 6.5 for
treatment recommendations.
6 Treatment guide Initial testing for ALL

6.2 AYAs with Ph-negative ALL
Chart 6.2.1 shows the recommended induction
therapy for AYAs with Ph-negative ALL. Induction
therapy is the first phase of treatment for ALL. The
goal of induction therapy is to kill all of the leukemia
cells in your bone marrow and put ALL into remission.
Thus, this phase is also referred to as remission
induction. Induction therapy consists of high doses of
chemotherapy drugs. It is very intensive, so you may
need to stay in the hospital for some or all of the time
while receiving treatment. Induction therapy usually
lasts about four weeks (one month).
Induction therapy
In general, there are two main options for induction
therapy. Receiving treatment on a clinical trial is
preferred if one is open and is the right fit for you. The
other option is to receive multiagent chemotherapy
based on a regimen designed for children with
ALL. This is called a pediatric-inspired regimen or a
pediatric-inspired protocol.
Pediatric-inspired induction regimens generally
include a combination of vincristine, pegaspargase,
a corticosteroid (prednisone or dexamethasone), and
doxorubicin or daunorubicin. Some regimens may
also include cyclophosphamide.
Pediatric-inspired regimens often start CNS
preventive treatment very early at the start of the
induction phase. For CNS-directed therapy, drugs
are often injected directly into the spinal fluid. This is
called IT therapy or IT chemotherapy. CNS-directed
therapy may include IT therapy with methotrexate
given alone or along with cytarabine and/or a
corticosteroid (dexamethasone or prednisone). When
all three IT therapy drugs are given, it is called triple
IT therapy. Methotrexate, cytarabine, and/or 6-MP
may also be given as IV injections. Rarely, CNS
disease may be found when ALL is first diagnosed.
In this case, your doctor may consider giving cranial
irradiation as well.
Induction therapy Response
• Clinical trial, or
• Pediatric-inspired multiagent
chemotherapy regimen
Chart 6.2.1 Remission induction
Complete remission
Consider monitoring for MRD with
flow cytometry and/or PCR
Treatment for refractory ALL
Less than complete
remission
6 Treatment guide AYAs with Ph-negative ALL

Response
At the end of induction therapy, your doctor will give
some tests to check how well treatment worked. A
treatment response is an outcome or improvement
related to treatment. To check the response, your
doctor will examine a sample of blood and bone
marrow with a microscope. The goal of induction
therapy is to result in a complete remission. 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 29 for more
details about treatment responses.)
If induction therapy resulted in a complete
remission, then your doctor may want to test for
MRD. MRD is when a very small (minimal) amount
of leukemia cells is still in your body after a course
of treatment. With MRD, the amount of leukemia
cells left is too small to be seen with a microscope.
PCR and flow cytometry are very sensitive tests
that doctors use to check for MRD. These tests find
leukemia cells in different ways. Flow cytometry finds
leukemia cells by the unique set of proteins on the
cell surface—called the immunophenotype. PCR
finds leukemia cells that have certain abnormal gene
changes. These tests can be done on a sample of
blood or bone marrow, but bone marrow is preferred.
Testing for MRD can help your doctor decide if more
intensive treatments are needed for consolidation
therapy.
If induction therapy resulted in less than a
complete remission, then a different treatment
regimen is recommended. ALL that is not in complete
remission after induction therapy is called refractory
ALL. This means that induction therapy wasn’t able to
kill enough leukemia cells in your body.
Next steps: 
If induction therapy resulted in a
complete remission, see Chart 6.2.2
for treatment recommendations. If
induction therapy resulted in less than
a complete remission, see Part 6.7 for
recommendations.

Chart 6.2.2 shows the treatments that are
recommended for AYAs with Ph-negative ALL after
induction therapy resulted in a complete remission.
Consolidation—also called intensification—is the
second phase of treatment for ALL. This may also
be referred to as postremission therapy since it is
given after ALL is in complete remission. The goal of
consolidation therapy is to kill any leukemia cells that
may still be in your body.
Consolidation therapy
Your doctor will consider many factors to help plan
consolidation therapy. This includes the ALL cell
subtype, the cytogenetic subtype, results of MRD
testing, and other prognostic factors. (See Treatment
planning in Part 3 for details.) Your doctor will also
take note of your general health, current symptoms,
and side effects. These factors can help your doctor
decide if you need and can tolerate more intensive
treatment for consolidation. There are two main
choices for consolidation therapy.
One option is to stay on multiagent chemotherapy
as outlined in the pediatric-inspired treatment
regimen. This may be an especially good choice
if sensitive tests used for MRD monitoring didn’t
find any leukemia cells. Consolidation therapy in
pediatric-inspired regimens often includes high-dose
methotrexate, cytarabine, 6-MP, and pegaspargase.
Consolidation therapy may include combinations of
drugs similar to those given during induction. Often,
chemotherapy drugs are given in higher (intensified)
doses during consolidation. CNS prophylaxis is also
usually given throughout the consolidation phase.
Consolidation therapy may last several months. The
total time and number of cycles varies depending on
the specific regimen used. The full treatment regimen
should be followed all the way through consolidation
and to the end of maintenance.
The other option is to consider an allogeneic SCT if
a well-matched donor has been found. An allogeneic
SCT is a very intensive treatment and may not be
a good choice for everyone. (See page 33 to read
more about treatment with an allogeneic SCT.) Your
doctor may consider this option if sensitive tests
found MRD after induction therapy. Your doctor
may also think this is a good choice for you if the
leukemia cells have certain poor risk features. A poor
risk feature is something that increases the chance
Consolidation therapy Maintenance therapy
Continue multiagent
chemotherapy regimen, or
Consider allogeneic SCT
if a donor is available
Chart 6.2.2 Postremission consolidation and maintenance
Maintenance for 2 to 3 years with:
• Weekly methotrexate,
• Daily 6-MP, and
• Monthly vincristine/prednisone pulses
Follow-up testing

(risk) that ALL might return (relapse) after treatment.
Examples of poor risk features include having fewer
than the normal number of chromosomes or having
five or more abnormal chromosome changes. After
completing consolidation with an allogeneic SCT, you
will begin follow-up testing. See Next steps at the end
of this section.
Maintenance therapy
The third phase of ALL treatment is called
maintenance. This phase is started after you finish
consolidation therapy. Maintenance therapy is
given to keep up (maintain) the good results of prior
treatments. The goal is to prevent a relapse after
completing induction and consolidation therapy. A
relapse is when leukemia cells come back after a
complete remission.
Most maintenance regimens are based on a
backbone of daily 6-MP and weekly methotrexate.
Often, vincristine and corticosteroids (prednisone
or dexamethasone) are also given as part of the
maintenance regimen. Maintenance therapy drugs
are often given in lower doses and cause fewer
side effects. CNS prophylaxis is also usually given
throughout the maintenance phase.
In general, maintenance therapy is given for
about two to three years. But, the total length of
maintenance varies depending on the treatment
regimen used. Pediatric-inspired regimens tend to
give maintenance therapy for a longer period than
adult regimens.
Next steps: 
After the allogeneic SCT or after
completing consolidation and
maintenance therapy, see Part 6.6 for
follow-up recommendations.

6 Treatment guide Older adults with Ph-negative ALL
6.3 Older adults with Ph-negative ALL
Chart 6.3.1 shows the recommended induction
therapy for older adults with Ph-negative ALL.
Induction therapy is the first phase of treatment for
ALL. The goal of induction therapy is to kill all of the
leukemia cells in your bone marrow and put ALL
into remission. Thus, this phase is also referred to
as remission induction. Induction therapy consists
of high doses of chemotherapy drugs. It is very
intensive. You may need to stay in the hospital some
or all of the time while receiving treatment. Induction
therapy usually lasts about four weeks (one month).
The leukemia cells can spread to the fluid around the
brain and spinal cord, called CNS disease. Treatment
to prevent CNS disease is given to all patients
during the induction phase. This is called CNS
preventive treatment or CNS prophylaxis. For CNS-
directed therapy, drugs are often injected directly
into the spinal fluid. This is called IT therapy or IT
chemotherapy. CNS-directed therapy may include IT
therapy with methotrexate given alone or along with
cytarabine and/or a corticosteroid (dexamethasone
or prednisone). When all three IT therapy drugs are
given, it is called triple IT therapy. Methotrexate,
cytarabine, and/or 6-MP may also be given as IV
injections. Rarely, CNS disease may be found when
ALL is first diagnosed. In this case, your doctor may
consider giving cranial irradiation as well.
Induction therapy
Often, age 65 is the cut-off for intensive treatment.
But, age alone is not a good gauge of a person’s
overall health or fitness for intensive treatment. When
choosing an induction regimen, your doctors will look
Induction therapy Response
Chart 6.3.1 Remission induction
Patients <65 years of
age or with no other
serious health problems
Patients >65 years
of age or with other
serious health problems
Clinical trial, or
Multiagent chemotherapy
Clinical trial,
Multiagent chemotherapy, or
Corticosteroids
Complete remission, consider
monitoring for MRD
Less than complete remission
Complete remission
Less than complete remission

Understanding Acute Lymphoblastic Leukemia

Understanding Acute Lymphoblastic Leukemia

Recommended

Recommended

More Related Content

Viewers also liked

Viewers also liked (17)

Similar to Understanding Acute Lymphoblastic Leukemia

Similar to Understanding Acute Lymphoblastic Leukemia (20)

More from Philippa Göranson

More from Philippa Göranson (7)

Understanding Acute Lymphoblastic Leukemia