The importance of physical therapy in children with leukaemia [610657]

The importance of physical therapy in children with leukaemia

International Childhood Cancer Day was celebrated worldwide on February 15, 2020,
which has been celebrated every year since 2011 when it was established in Luxembourg to raise
awareness and awareness of the importance of this problem and the challenges, they face children
and adolescents and their families. As well as the need for all children anywhere in the world to
have access to accurate and timely diagnosis and treatment (Brand, Wolfe, Samsel 2017:13 )1.
The diagnosis of childhood cancer always has a g reat impact on the family, which turns to
care for the little one. Physiotherapy is a key and essential element within the multidisciplinary
team involved in recovery, as well as in the prevention of sequelae caused by the development and
evolution of the disease itself or secondary to the cancer treatment it receives. Prolonged sedentary
lifestyle during hospital stays also affects the onset of stages of weakness and muscle fatigue2.
The most common conditions among children with the disease are mobility deficits, loss
of strength, neurological disorders, breathing difficulties or even psychomotor retardation, in
younger children. In this sense, the Physiotherapy treatment is always or iented towards exercises
of coordination, balance, proprioception, control of orthostatism, re-education of gait and activities
of a playful nature and social skills, which raises their self -esteem and strength to normalize the
situation, always with the i nvaluable help of parents and relatives (Bužgová, Kozáková,
2019:250)3.
Acute lymphoblastic leukaemia is one of the most common oncological processes in the
paediatric population worldwide. Fortunately, the survival rate among patients with this type of
disease is increasing thanks to advances in medicine in cancer treatments. But these same
treatments can often cause side effects that affect the quality of life, aerobic capacity, movement
functionality, flexibility, and strength, hindering your activitie s of daily living (Terwilliger, Hay,
2017)4.
The practice of physiotherapy with these patients consists mainly of the pattern of physical
exercise in search of an improvement in the qualities mentioned above, patients, mainly in the
musculoskeletal syste m and quality of life. It seems that the practice of physical exercise is not
related to the improvement of the quality of life or improvement of the range of movement in these

1 https://internationalchildhoodcancerday.org/
2 Brand S, Wolfe J, Samsel C. The Impact of Cancer and its Treatment on the Growth and Development of the
Pediatric Patient. Curr Pediatr Rev. 2017;13(1):24 -33. doi: 10.2174/1573396313666161116094916. PMID:
2784 8890; PMCID: PMC5503788.
3 Bužgová R, Kozáková R. Informing patients with progressive neurological disease of their health status, and their
adaptation to the disease. BMC Neurol. 2019 Oct 25;19(1):250. doi: 10.1186/s12883 -019-1488 -y. PMID: 31653233;
PMCID : PMC6815047.
4 Terwilliger T, Abdul -Hay M. Acute lymphoblastic leukaemia: a comprehensive review and 2017 update. Blood
Cancer J. 2017 Jun 30;7(6 ): e577. doi: 10.1038/bcj.2017.53. PMID: 28665419; PMCID: PMC5520400.

patients. On the other hand, there are indications that it improves aerobic cap acity, movement
functionality, and the strength of certain muscles. More studies with better clarification in the
design of the exercise program and with groups of patients who are in the same phase of cancer
treatment are needed to reach more relevant con clusions (McPhail, Waite, 2014 )5.
I have decided to carry out this thesis to learn how to work with these types of patients
since they are knowledge that is not covered in depth during the degree.
Since I had to do a thesis related to paediatrics , I considered the option of developing it
concerning the world of oncology. Due to the complexity and breadth of this area, I finally opted
for leukaemia , but for the same reason I had to limit much more and finally, I decided to choose
the most common on cological process in patients within this age range: acute lymphoblastic
leukaemia . Another aspect that motivated me with this choice has been that from physiotherapy,
research in this type of disease is scarce and for this reason, physiotherapists must de lve deeper
into them, always respecting the guidelines of the different medical specialists take charge of
managing the disease; mainly haematologists , oncologists and paediatricians .
The main goal throughout the papers is to know the scientific evidence o n the
physiotherapy approach with patients with ALL, in search of trying to minimize or reduce to the
maximum the secondary effects that can trigger the oncological treatments they receive, mainly
on the musculoskeletal system and quality of life.
In this thesis, a systematic review is carried out to find out the efficacy of the
physiotherapeutic approach in patients with ALL in children.
The keywords used in digital researches were: „acute lymphoblastic leukaemia ”,
„paediatric ”, „children ”, „physiotherap y”, „physical therapy ”, „physical exercise ” and „physical
medicine ”.
The Boolean connectors „AND ” and „OR” were used together in the databases that allowed
it and had an enormous impact in finding the necessary information.
The PICO strategy was used to carry out the searches (Population, intervention, comparison
and results) meaning: patients with ALL in chi ldren (the terms „acute lymphoblastic leukaemia ”,
„children ” and „paediatric ” were used; intervention refers to physiotherapy treatment or related
to it (the terms used: „physiotherapy ”, „physical therapy ” and „physical exercise ”).
Since the databases do not offer the possibility of applying the same filters , they are applied
manually and lead the search for the same direction, in case it is not possible

5 McPhail SM, Waite MC. Physical activit y and health -related quality of life among physiotherapists: a cross –
sectional survey in an Australian hospital and health service. J Occup Med Toxicol. 2014 Jan 9;9(1):1. doi:
10.1186/1745 -6673 -9-1. PMID: 24405934; PMCID: PMC3896696.

Some of the inclusion criteria consist in articles related to ALL, to some type of
physiotherapeutic t reatment, articles that are randomized clinical trials (RCTs), that study patients
with ALL and subjects between 0 and 18 years old, articles in the English language.
For all the reasons above, the digital searches of articles on the subject to be treated were
carried out in the following databases: “PubMed ”: acute lymphoblastic leukaemia AND (children
OR paediatric ) AND (physiotherapy OR physical exercise OR physical therapy) resulting in 200
plus articles. Then the filters “Randomized Controlled Trial ” (“Article types ”), “Full text ” (“Text
availability ”), “English ” (“Languages ”) were applied, resulting in 15 ECAs in English.); on
“PEDro ”, the following searches were performed: acute lymphoblastic leukaemia AND physical
exercise resulted in 6 resul ts, of which two are excluded as they are systematic reviews, giving a
final result of 4 articles, acute lymphoblastic leukaemia AND physical therapy with two results
and acute lymphoblastic leukaemia AND physical medicine with one single result that is ex cluded
as it is a systematic review; on „Trip Database ”, acute lymphoblastic leukaemia AND (children
OR paediatric ) AND (physiotherapy OR physical exercise OR physical therapy) resulted in 321
articles ; on “American Cancer Society ”, by typing “ leukaemia ” and “children ”, 6 downloadable
PDF format files could be downloaded; on “OECD library ”, by typing the same key words, 3
readable results were offered; on “Global Cancer Observatory ”, while clicking on the fourth
section called “Childhood Cancer ”, two articles can be easily found.

1. General

Leukaemia is defined as hematopoietic cell neoplasms that initially proliferate in the bone
marrow and subsequently spread to the blood and even to other tissues. These cells mature and
can accumulate in the bone marrow, preventing normal haematopoiesis . In this way, most of the
lymphoid or myeloid elements in the blood can become immature.
In a very general way, it can be said that leukaemia ’s divided into two large groups:
myeloid and lymphoid. Although we can also talk about plasma cell leukaemia or erythroleukemia .
Lymphoid and myeloid leukaemia , in turn, can be acute or chronic. Thus, on the one hand,
we have acute lymphatic leukaemia , also called acute lymphoblastic leukaemia and acute myeloid
leukaemia . On the other hand, we find chronic lymphoid leukaemia and chronic myeloid
leukaemia (Greim, Kaden, Larson, Palermo, Rice, Ross, Snyder, 2014: 7 -31)6. Within all
leukaemia , acute lymphoblastic leukaemia (ALL), is the most typical cancer in the European child
population, with around 40 cases per million children/year. It is also calculated that the ratio
between boys and girls is 2: 1 respectively and that the age range in w hich there is the greatest
chance of suffering from it is between 2 and 5 years (National Research Council, 2003)7.
Most of these types of patients will suffer side effects as a result of the cancer treatment
they receive to combat their disease. Neuromus cular and musculoskeletal functions will be
compromised. Therefore, in these patients, we can find a decrease in fine and gross motor skills,
poor physical activity, paraesthesia , pain, muscle cramps, muscle weakness and reduction of the
dorsiflexion angle due to a reduction in the extensibility of the twin and soleus, among others.
problems. To all these effects, it is necessary to add the high probability that these patients have
of suffering osteopenia and therefore developing osteoporosis in the future.
The practice of physiotherapy with this type of patient will consist of applying an exercise
program to try to minimize all the effects described above, in search of an improvement in the
quality of life, strength, flexibility, aerobic capacity and theref ore be able to achieve better
movement functionality so that they can better cope with the activities of daily life.
For this, the physiotherapist must know what type of exercises to guide and how to guide
them, without ignoring the assessment methods that will allow him to know if his treatments are
having effects and if they do know if they are positive or negative. To practice physiotherapy with

6 Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D, Snyder R. The bone marrow niche, stem cells,
and leukaemia: impact of drugs, chemicals, and the environment. Ann N Y Acad Sci. 2014 Mar;1310(1):7 -31. doi:
10.1111/nyas.12362. Epub 2014 Feb 4. PMID: 24495159; PMCID: P MC4002179.
7 National Research Council. Institute of Medicine, National Cancer Policy Board, Childhood Cancer Survivorship:
Improving Care and Quality of Life, National Academies Press, USA, 2003, p. 21.

these patients, it is necessary to know some tests that help us objectively assess certain qualities in
them (Zaino, Marchese, Westcott, 2004)8.
– Time up and downstairs – to carry out this test, the child must be able to go up and down
14 steps. The participant can go up and down the steps using the technique he wants, as long as he
goes up and down in front. The physical therapist gives an order and the participant begins to
climb. On the step, Participants must run in a straight line when they reach one end they must pivot
and reach the other end, and so on. The test may end for two reasons, either bec ause the participant
stops due to fatigue, or because he no longer reaches the other extreme before the recording sounds
twice in succession. Depending on the stage in which the participant stops and their age, the
maximum Vo2 is calculated, using differen t standard equations.
– Time 9-minute walk -test – to carry out this test, you need 2 cones separated from each
other by 30 meters. Participants are asked to walk as quickly as possible between the two cones,
for a time of 9 minutes. There are a few variati ons that allow patients to run. Once the time has
finished, the meters that each participant has walked are recorded. A higher result indicates better
cardiorespiratory conditions on the part of the participant.
– Movement Assessment Battery for Children – in this test, the child must perform a series
of actions that involve both fine and gross motor skills. These actions are divided into three main
groups: manual dexterity, aim and catch and balance tasks. There are three age ranges in which
the norms are different, children between 3 and 6 years old, between 7 and 10 years old and
between 11 and 16 years old. These age ranges will be differentiated when obtaining the score for
each task. Using tables that associate the score with age, percentiles are achie ved. As usual, the
higher the score, the better the motor skills the participant has.
– Bayley Scales of Infant Development – this scale is used to assess the mental and
psychomotor development of children between one year and three years and 6 months.
The questions on the scale are divided into two large blocks: 178 mental development
questions and 111 psychomotor development questions. Not all the participants pass all the
questions, the total number of them may vary due to their age. We are more interest ed in the part
that is in charge of psychomotor development. Once again, a higher score indicates a greater
development, in this case, both for the mental aspect and for the psychomotor aspect.
– Sit and reach – to carry out this test, the participants sit seated on the floor, with knees and
legs together, with the soles of the feet touching the box.
A meter will be placed in the box, in such a way that position 0 of the meters corresponds
to the height of the feet.

8 Zaino CA, Marchese VG, Westcott SL. Timed up and downstairs test preliminary reliability and validity of a new
measure of functional mobility. Pediatr Phys Ther. 2004.

2. Leukaemia in children

Genetic syndromes are diseases or disorders caused by a change (mutation) in one or more
genes. The following genetic syndromes may expand the threat of generating childhood
leukaemia9.
Down syndrome is associated with intellectual disability, a characteri stic facial appearance
and poor muscle tone. Children with Down syndrome can be born with a variety of birth defects.
Their risk of having multiple medical conditions, including certain types of cancer such as
leukaemia is higher.
Bloom syndrome is the res ult of numerous abnormal chromosomes. Children with Bloom
syndrome are usually shorter than average, have a high voice, and have a characteristic facial
appearance. A large number of abnormal chromosomes creates a high risk of developing different
types of childhood cancer, including leukaemia , osteosarcoma and Wilms tumour .
Fanconi ’s anaemia affects the bone marrow so that it does not make enough healthy cells
like red blood cells, white blood cells or platelets. Children with Fanconi ’s anaemia are more li kely
to have leukaemia .
Ataxia -telangiectasia (AT) affects the nervous system, the immune system and other
systems of the body. Children with AT often have a weakened immune system and their risk of
cancer is higher, especially for lymphoma and leukaemia .
Neurofibromatosis type 1, also called von Recklinghausen disease, affects the development
and growth of nerve cells (neurons) and causes tumours to form on nerves. Children with type 1
neurofibromatosis are more likely to have certain cancers, including br ain cancer, leukaemia ,
neuroblastoma and rhabdomyosarcoma.
Wiskott -Aldrich syndrome influences blood cells and cells related to the immune system.
Children with this syndrome have a low platelet count, which can lead to a tendency to bruise and
bleed. Thei r risk of infection is higher because certain immune cells, such as T and B cells, do not
work as they should. Children with Wiskott -Aldrich syndrome are more likely to have certain
types of cancer, such as leukaemia and lymphoma.
Klinefelter syndrome affects human sexual development and produces small testicles,
enlarged breasts and a lack of easy or body hair. This syndrome has been linked to the increased
risk of childhood leukaemia .
Li-Fraumeni syndrome greatly increases the ris k of developing several types of cancer,
including breast cancer, osteosarcoma, soft tissue sarcoma, brain cancer and leukaemia .

9 https://www.cancer.ca/en/cancer -information/cancer -type/leukemia -childhood/risks/?reg ion=on

Schwachman -Diamond syndrome affects many parts of the body, including the bone
marrow, pancreas, and skeleton. Children with th is syndrome often see a drop in the level of all
types of blood cells. This causes more infections, fatigue, weakness as well as a tendency to bruise
or bleed. Their risk of developing childhood leukaemia is also higher.
A child with a sibling who has leukaemia is slightly more likely to have leukaemia than
children in the general population. In identical twins, the risk is much higher. The risk is higher at
birth and decreases until the child is 7 years old.
A risk factor is something like a behaviour , sub stance, or condition that increases the risk
of developing cancer. Most cancers are caused by many risk factors. However, childhood
leukaemia can occur in a child who does not have any of the risk factors described below.
Childhood leukaemia is more common among white and Hispanic children. About 75% of
all childhood leukaemia is acute lymphoblastic leukaemia (ALL), and most of these ALL occur in
children aged 1 to 4 years. More boys than girls are affected. About 20% of all childhood
leukaemia are acute my eloblastic leukaemia (AML). More girls than boys are affected (Belson,
Kingsley, Holmes, 2007:138 -45)10.
Most risk factors cannot be changed. This means that you cannot change them. Until more
is known about these risk factors, there is no specific way to r educe the risk. Risk factors are
usually ranked from most important to least important. But in most cases, it is impossible to
classify them with absolute certainty. There is convincing evidence that exposure to radon and less
exposure to infections increa se the risk of childhood leukaemia . Researchers are unable to
definitively establish this link or that the studies have produced different results. More research is
needed to determine if the two previously mentioned are risk factors for childhood leukaemi a.

10 Belson M, Kingsley B, Holmes A. Risk factors for acute leukaemia in children: a review. Environ Health
Perspect. 2007 Jan;115(1):138 -45. doi: 10.1289/ehp.9023. Erratum in: Environ Health Perspect. 2010 Sep;118(9 ):
A380. PMID: 17366834; PMCID: PMC1 817663.

3. Types of leukaemia in children/adults

Different types of leukaemia are mainly based on:
– if the leukaemia is acute (fast -growing) or chronic (slower growing)
– if the leukaemia starts in myeloid cells or lymphoid cells
When doctors know the specific type of leukaemia a child has, they can make a better
prognosis and select the best treatment11.
Acute leukaemia . Most childhood leukaemia is acute. This leukaemia can progress rapidly
and generally must be treated immediately. The two main types of acute leukaemia are:
– acute lymphocytic leukaemia (lymphoblastic): About 3 out of 4 leukaemia in children are acute
lymphocytic leukaemia (ALL). This leukaemia originat es from very young forms of white blood
cells called lymphocytes.
– acute myeloid leukaemia (AML): This type of leukaemia , also called acute myelogenous
leukaemia , acute myelocytic leukaemia , or acute non -lymphocytic leukaemia , accounts for the
majority of remaining cases of leukaemia in children. Acute myeloid leukaemia (AML) starts from
the myeloid cells that normally make up white blood cells (which are not lymphocytes), red blood
cells, or platelets (Terwilliger, Abdul -Hay, 2017)12.
In rare cases, acute leukaemia may have characteristics of ALL and AML. These types of
leukaemia can be called mixed lineage leukaemia , undifferentiated acute leukaemia , or mixed
phenotypic acute leukaemia (MPAL). In children, they are generally treated like ALL and
generally respond to this treatment like ALL. Both ALL and AML have subtypes, which are
described in Child Leukaemia Subtypes.
Chronic leukaemia . They are rare in children. This leukaemia tends to grow more slowly
than acute leukaemia , although they are also more difficult to cure. Chronic leukaemia can be
divided into two main types:
Chronic myeloid leukaemia (CML): It is also known as chronic myelogenous leukaemia ,
and it is rare in children. Treatment is similar to that used in adul ts (see Treatment for Children
with Chronic Myeloid Leukaemia [CML]). For more information on CML, see Chronic Myeloid
Leukaemia .
Chronic Lymphocytic Leukaemia (CLL): This leukaemia occurs very rarely in children.
For more information, see Chronic Lymphocy tic Leukaemia (CLL).

11 https://www.cancer.org/cancer/chronic -myeloid -leukemia/about/what -is-cml.html
12 Terwilliger T, Abdul -Hay M. Acute lymphoblastic leukaemia: a comprehensive review and 2017 update. Blood
Cancer J. 2017 Jun 30;7(6 ): e577. doi: 10.1038/bcj.2017.53. P MID: 28665419; PMCID: PMC5520400.

Juvenile myelomonocytic leukaemia (JMML) is a rare type of leukaemia that is neither
chronic nor acute. It starts from myeloid cells but generally does not grow as fast as AML or as
slowly as CML. This leukaemia occurs more frequently in young children (the average age of 4
years). Symptoms may include pale skin, fever, coughing, bruising or bleeding that occurs easily,
difficulty breathing (due to too many white blood cells in the lungs), a rash, and an enlarged spleen,
liver, and lymp h node. For information on treating JMML, see Treatment for Children with
Juvenile Myelomonocytic Leukaemia (JMML) (Lee, Baek, Kim, Park, Hwang, Kook ,2019:63 –
73)13.
Bone marrow, blood, and normal lymphatic tissue. To understand leukaemia , it helps to
know about the bone marrow and the blood and lymphatic systems. The bone marrow is the soft
part of the interior of certain bones that is made up of blood -producing cells , fat cells, and
supporting tissues. A small number of blood -producing cells are stem cells.
Blood stem cells undergo a series of changes to make new blood cells. During this process,
the cells become lymphocytes (a type of white blood cell) or other blood -producing cells, which
are types of myeloid cells. Myeloid cells could result in blood cells, white blood cells ( more than
just lymphocytes), or platelets.
Red blood cells carry oxygen from the lungs to all other tissues in the body and return
carbon diox ide to the lungs to be removed.
Platelets are cell fragments produced by a type of bone marrow cell called a
megakaryocyte. Platelets are important in stopping bleeding by sealing small holes in the blood
vessels. White blood cells help the body fight infe ction. There are different types of white blood
cells14:
❖ Lymphocytes are mature cells that develop from lymphoblasts, a type of blood -producing
cell in the bone marrow. Lymphocytes are the main cells that make up the lymphatic tissue
that is an important pa rt of the immune system. Lymphatic tissue is found in the lymph
nodes, the thymus (a small organ behind the sternum), the spleen, the tonsils and adenoid
glands, and the bone marrow. It is also scattered throughout the digestive system and
respiratory syst em. There are two main types of lymphocytes: B cells and T cells (ALL,
the most common type of childhood leukaemia , can start in either B cells or T cells). For
more information, see Child Leukaemia Subtypes.
❖ Granulocytes are mature white blood cells that develop from myeloblasts, a type of blood –
producing cell in the bone marrow. Granulocytes have granules that appear as spots when

13 Lee HG, Baek HJ, Kim HS, Park SM, Hwang TJ, Kook H. Biphenotypic acute leukaemia or acute leukaemia of
ambiguous lineage in childhood: clinical characteristics and outcome. Blood Res. 2019 Mar;54(1):63 -73. doi:
10.5045/b r.2019.54.1.63. Epub 2019 Mar 21. PMID: 30956966; PMCID: PMC6439300.
14 https://www.cancer.org/cancer/chronic -lymphocytic -leukemia/about/normal -tissue.html

viewed under a microscope. These granules contain enzymes and other substances that can
destroy germs like bacteria.
The three types of granulocytes, (neutrophils, basophils, and eosinophils) are distinguished
by the size and colour of the granules when viewed under a microscope.
Monocytes develop from blood -producing monoblasts in the bone marrow and are related
to gran ulocytes. After circulating in the bloodstream for about a day, monocytes enter body tissues
to turn out to be macrophages, which can break some germs through surrounding and digesting
them . Leukaemia originates from the bone marrow.
Leukaemia cells can accumulate there and outnumber normal cells. Most of the time,
leukemic cells enter the bloodstream fairly quickly. Some types of leukaemia can also spread to
other parts of the body, such as the lymph nodes, spleen, liver, central nervous system (the brain
and spinal cord), testicles, or other organs. Some other types of childhood cancer, such as
neuroblastoma or rhabdomyosarcoma, start in other organs and can spread to the bone marrow,
but these cance rs are not leukaemia .

4. Diagnosis

Most of the signs and symptoms of childhood leukaemia are most likely due to other
causes, such as infections. Still, it is important to tell your child ’s doctor about the symptoms
immediately so that the cause is found and treated, if necessary.
Exams and tests will be done to determine the cause of the sym ptoms. If leukaemia is
discovered, additional tests will be required to determine the type and subtype of leukaemia and
decide how it should be treated. It is important to diagnose childhood leukaemia as early as
possible and determine the type of leukaemi a so that treatment can be tailored to the child so that
he has the best difficulties in success. If your child has signs and symptoms that have leukaemia ,
the doctor conducts a comprehensive medical history to get information about the symptoms and
to fin d out how long they have had. The health practitioner may additionally ask about exposure
to possible chance factors . A family history of cancer, especially leukaemia , may also be
important15.
During the physical exam, the doctor looks for any enlarged lymp h nodes, areas of bleeding
or bruising, or possible signs of infection. Your eyes, mouth, and skin will be examined closely,
and an examination of the nervous system may be done. The abdomen (child) will be palpated to
try to detect signs of an enlarged sp leen or liver.
If the doctor thinks your child may have leukaemia , he will need to test blood and bone
marrow samples to confirm the suspicion. For some tests, your child ’s doctor may recommend a
paediatric oncologist, a doctor who specializes in treating cancers in children (including
leukaemia ). If leukaemia is found, we can also do other types of tests to help guide treatment
(Lang, Kansy, 2014)16.
Blood tests are the first tests done to detect leukaemia . Blood samples are usually taken
from a vein in the arm, although in infants and young children, they can be taken from other veins
(such as from the feet or scalp) or a finger puncture.
The tests done on these samples are usually blood counts and blood smears. A complete
blood count (total blood count, CBC) is done to determine the number of blood cells of each type
present in the blood. A blood smear involves spreading a small blood sample on a glass slide and
viewing it under a microscope. Abnormal numbers of blood cells and changes in the way these
cells look can make your doctor suspect leukaemia .

15 https://www.cancer.org/cancer/leukemia -in-children/detection -diagnosis -staging/how -diagnosed.html
16 Lang S, Kansy B. Cervical lymph node diseases in children. GMS Curr Top Otorhinolaryngol Head Neck Surg.
2014 Dec 1; 13: Doc 08. doi: 10.3205/cto000111. PMID: 25587368; PMCID: PMC4273169.

Most children with leukaemia will have too many white blood cells and not enough red
blood cells or enough platelets. Many of the white blood cells will be blasts, a type of young cell
normally found only in the bone marrow. Although these findings may cause a doctor to suspect
that a child has leukaemia , the presence of the disease generally cannot be diagnosed with certainty
without looking at a sample of bone marrow cells (PDQ Paediatric Treatment Editor ial Board,
2019)17.
A bone marrow aspirate and biopsy are tests that are usually done at the same time. Samples
are usually taken from the back of the pelvic bones (hip), although sometimes they can be taken
from the front of the pelvic bones or other bones . Before testing, the skin over the hip is cleaned
and numbed by injecting a local anaesthetic or applying an anaesthetic cream. In most cases, the
child also receives other medicines to make him sleepy or even asleep during tests. For a bone
marrow aspira te, a thin, hollow needle is inserted into the bone, and a syringe is used to aspirate a
small amount of liquid bone marrow.
A bone marrow biopsy is usually done immediately after the aspirate. A small piece of
bone and marrow is removed with a slightly la rger needle to pierce the bone. Once the biopsy is
done, the pressure is applied to the site to help stop any bleeding. Then, the bone marrow samples
are sent to a laboratory for further analysis.
Bone marrow tests are used to diagnose leukaemia , although they may also be repeated
later to see if the leukaemia is responding to treatment. This test is used to detect leukaemia cells
in the cerebrospinal fluid (CSF), which is the fluid that bathes the brain and spinal cord.
For this test, the doctor first applies an anaesthetic cream to an area on the lower back over
the spine. The doctor usually also gives the child medicine to make him sleep through the
procedure. A small, hollow needle is then inserted between the bones of the spine to extract some
fluid, which is sent to a laboratory for further analysis18.
In children who have been diagnosed with leukaemia , lumbar punctures can also be used
to administer chemotherapy drugs into the CSF to prevent or treat the spread of leukaemia to the
spinal cord and brain (called intrathecal chemotherapy). This type of biopsy is important in
diagnosing lymphomas, but it is rarely needed in children with leukaemia . To perform this
procedure, a surgeon cuts the skin to remove an entire lymp h node (called an excisional biopsy).
If the node is located near the surface of the skin, this is a simple operation. However, it is more
complex if the node is inside the chest or abdomen. More often, the child will need general
anaesthesia (the child is asleep). For additional testing, all blood, bone marrow, and other samples

17 PDQ Pediatric Treatment Editorial Board. Childhood Acute Myeloid Le ukemia/Other Myeloid Malignancies
Treatment (PDQ®): Patient Version. 2019 Oct 17. In: PDQ Cancer Information Summaries [Internet]. Bethesda
(MD): National Cancer Institute (US); 2002 -. Available from: https://www.ncbi.nlm.nih.gov/books/NBK65864/
18 https:// www.cancer.org/cancer/leukemia -in-children/detection -diagnosis -staging/how -diagnosed.html

are sent to a laboratory. All samples were taken (blood, bone marrow, lymph node tissue, or
cerebrospinal fluid) are examined under a microscope. Samples are exposed to chemical st ains
(dyes) that can cause changes in the colours of some types of leukaemia cells.
Doctors will look at the size, shape, and staining patterns of blood cells in samples to
classify them into specific types. An elemental factor is whether the cells look m ature (like normal
blood cells) or immature (lacking the characteristics of these normal cells) (PDQ Paediatric
Treatment Editorial Board, 2019)19.
The most immature cells are called blasts. The presence of too many blasts in the sample,
especially in the blood, is a typical sign of leukaemia . An important characteristic of a bone marrow
sample is its cellularity.
The normal bone marrow contains seve ral blood -producing cells and fat cells. A marrow
that has too many blood -producing cells is said to be hypercellular. If too few blood -forming cells
are found, the marrow is considered to be hypocellular. These tests are used to classify leukaemia
cells b ased on certain proteins present in or on the cells (immunophenotype). This type of test is
very helpful in determining the exact type and subtype of leukaemia . It is most often done on bone
marrow cells, but it can also be done on blood cells, lymph nodes , and other body fluids.
For flow cytometry or immunohistochemistry, cell samples are treated with antibodies that
are proteins that bind to other proteins on the cells.
In immunohistochemistry, cells are then examined under a microscope to see if the
antibodies bind to them (meaning they contain those proteins), while a special machine is used for
flow cytometry. Flow cytometry can also be used to calculate the amount of DNA in leukemic
cells. This is important to know, especially in ALL, since cells with more DNA than normal (a
DNA index of 1.16 or more) are often more sensitive to chemotherapy, and this leukaemia have a
better prognosis (outlook).
Flow cytometry can also be used to measure treatment response and the existence of
minimal residual disease (MRD) in some types of leukaemia (Bennett, Orazi, 2009:264 -8)20.

19 PDQ Pediatric Treatment Editorial Board. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Patient
Version. 2019 Jul 23. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute
(US); 2002 -. Available from: https://www.ncbi.nlm.nih.gov/books/NBK65947/
20 Bennett JM, Orazi A. Diagnostic criteria to distinguish hypocellular acute myeloid leukaemia from hypocellular
myelodysplastic syndromes and aplastic anaemia: recommendations for a standardized approach. Haematologica.
2009 Feb;94(2):264 -8. doi: 10.3324/haematol.13755. Epub 2009 Jan 14. PMID: 19144661; PMCID: PMC2635414.

5. Causes

For the majority of people with leukaemia , there is no way to determine the cause. In some
cases, however, specific risk factors can be specified: history of chemotherapy or radiotherapy.
exposure to high doses of radiation or benzene (a substance found in unleaded gasoline, tobacco
smoke and chemical plants) , family history , a genetic defect, such as a defect in chromosome 22
(sometimes called the Philadelphia chromosome) and genetic disorders like Down syndrome and
Fanconi disease.
All forms of cancer that spread throughout the body (malignant forms), including
leukaemia , are thought to be caused by genetic abnormalities (mutations). In leukaemia , the
abnormality causes damage to stem cells in the bone marrow.
These special cells help make all the other cells in the blood. There is then a disorderly
growth of cells, without any form of restriction.
Leukaemia can cause a lack of functional white blood cells, which disrupts the functioning
of the immune system or leads to an accumulation of supernumerary white blood cells.
In acute leukaemia , most of the supernumerary white blood cells are immature, while in
chronic leukaemia these cells are mature but do not function normally.
In both cases, however, the production of platelets (the cells that make blood clot) becomes
insufficient, which ca uses excessive bleeding. Even minor bumps or injuries can cause large
bruising or prolonged bleeding, and small red spots can appear under the skin. As the immune
system is in poor condition, infections are more common.
The lymph nodes and spleen may incr ease in size, causing pain in the left side of the
abdomen. If abnormal cells accumulate in the brain and spinal cord (for example, in cases of
AML), this results in vomiting and headache. Sometimes abnormal cells build up in the skin,
causing small bumps (chloromas) or rashes. The shortage of red blood cells makes the complexion
pale and leads to fatigue and shortness of breath (Poynter, Richardson, Roesler, Blair, Hirsch,
Nguyen, Cioc, Cerhan, Warlick , 2017:23 -33)21.

21 Poynter JN, Richardson M, Roesler M, Blair CK, Hirsch B, Nguyen P, Cioc A, Cerhan JR, Warlick E. Chemical
exposures and risk of acute myeloid leukaemia and myelodysplastic syndromes in a population -based study. Int J
Cancer. 2017 Jan 1;140(1):23 -33. doi: 10.1002/ijc.30420. Epub 2016 Sep 24. Erratum in: Int J Can cer. 2019 Aug
1;145(3 ): E15. PMID: 27603749; PMCID: PMC5245124.

6. Treatment

Since CLL does not cause a major change in the blood, it can remain stable for years and
requires no treatment. However, the doctor may decide to prescribe a low -energy treatment to keep
the number of blood cells at an adequate level. More rarely, more agg ressive treatment will be
needed to increase the number of white blood cells or to treat complications such as anaemia .
Doctors usually treat CML with a class of drugs called tyrosine kinase inhibitors. This type
of treatment is called targeted molecular t herapy and works by blocking the ability of abnormal
cells to over -stimulate the production of various types of blood cells. In many cases, this treatment
removes the signs of leukaemia and is said to be in remission (the stage at which normal levels of
blood cells are restored).
The remission may be short -lived, but when it goes on for a long time, there are no more
abnormal cells in the blood. White blood cell count and general health should be monitored, but
people can usually continue with their normal activities during treatment. More energetic
treatments are prescribed to induce a remission of acute leukaemia – a stage when the normal
number of blood cells is restored. To achieve this result, different combinations of chemotherapy
drugs are used. Duri ng the treatment of acute leukaemia , the levels of certain blood components
may drop, leading to anaemia (lack of red blood cells) or an increased risk of infection. When the
number of red blood cells or platelets becomes too low, a blood transfusion may b e necessary.
Antibiotics can also be administered to eliminate infections. Side effects of chemotherapy include
nausea, vomiting and hair loss.
Bone marrow transplantation is the only way to cure CML, but it is rarely used today
because of the success of t yrosine kinase inhibitors in acting on the Philadelphia chromosome and
inducing remission. Bone marrow transplantation is more common in the treatment of AML and
ALL when chemotherapy alone is unlikely to cure. This treatment can only be performed if there
is an exact match between the donor ’s bone marrow and that of the person receiving the transplant.
Otherwise, the body considers the transplanted cells as „foreign ” and rejects them (Haskin, Kogan,
2018:51 -56.)22.

22 Haskin G, Kogan M. Case Report of Unexpectedly Long Survival of Patient with Chronic Lymphocytic
Leukemia: Why Integrative Methods Matter. Integr Med (Encinitas). 2018 Feb;17(1):51 -56. PMID: 30962776;
PMCID: PMC6380985.

7. Adverse effects of treatment

The „iatrogenic ” effects depend on the protocols used (surgery, radiotherapy,
chemotherapy, combination, doses …) but also on the type of cancer and the age of the child.
Among the most severe, let us mention the second cancers, cardiovascular and cerebrovascular
diseases, hormonal disorders . The work carried out in recent years has made it possible to better
understand them to improve the monitoring of adults cured of paediatric cancer as well as the
benefit report/risks of current therapies.
Childhood cancer is relatively rare since it represents only 1% of all cancers screened 1. In
France, around 1,700 cases 2 are discovered each year in children under 15, with a peak around
the age of 2 years. The most common cancers affect the brain (brai n tumours ), blood ( leukaemia )
and the lymphatic system (lymphomas).
Leukaemia is the most common cancer in children: it represents more than 30% of cancers
diagnosed in young people under the age of 15 worldwide. Its causes are poorly understood but
are am ong the risk factors for hereditary factors such as Down syndrome (Down syndrome) and
family history of leukaemia, and non -hereditary factors such as exposure to ionizing radiation.
There are different types of leukaemia, but about three -quarters of childh ood cases are acute
lymphoblastic leukaemia (ALL). Acute myeloid leukaemia comes second.
The prognosis differs based on various factors, including age, initial white blood cell count,
gender, the initial reaction to induction therapy, and the type of leuka emia . After five years of
complete remission, children with acute leukaemia are considered cured because relapses are rare
beyond this period (PDQ Pediatric Treatment Editorial Board,2020 )23.
In 2012, 4.7 new cases of leukaemia per 100,000 children between the ages of 0 and 14
were registered, on average, in OECD countries. The differences between countries are significant:
the incidence rates in Germany and Finland are high, 7 per 100,000 children, while they are 3 per
100,000 in Iceland and Greece. South Africa, India and China also have low incidence rates, less
than 3 per 100,000 children.
The net five -year survival rate for acute lymphoblastic leukaemia in children in the summer
averaged 86.7% over the 2010 -14 period in OECD countries. Although the prognosis for ALL is
considered more favourable in girls than boys, the difference in net survival rates is not statistically
significant in the majority of countries, except for Estonia, where the survival rate of girls is
slightl y higher.

23 PDQ Pediatric Treatment Editorial Board. Late Effects of Treatment for Childhood Cancer (PDQ®): Health
Professional Version. 2020 Apr 2. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National
Cancer Institu te (US); 2002 -. Available from: https://www.ncbi.nlm.nih.gov/books/NBK65832/

Over the years, the net five -year survival rate for children The LAL obtained has increased
in OECD countries. This improvement is mainly due to advances in chemotherapy and the stem
cell transplant technique. However, not all countries have even benefited from these medical
advances. Survival rates are high in Finland (95.2%), Denmark (94.0%), but low in Mexico
(52.7%) and Chile (63.9%). They are also low in China (57.7%), Brazil (66.0%) and Colombia
(68.9%). These countries could increase the ch ances of survival for ALL children by improving
access to effective treatments, namely extending coverage and quality health care, by approved
professionals, in specialized centres . Some of these countries are making progress and have
improved the quality of care for children with cancer and the quality of their care. Chile has thus
integrated access to health care for these children into its guaranteed health insurance scheme and,
despite the persistent shortage of qualified professionals in specialized centres , the quality of care
provided by different providers has standardized (OECD, 2018 ).
A gradual improvement in the mortality rate childhood leukaemia can also be observed in
OECD countries, the latter being less than 1 per 100,000 children in most of t hese in 2012. It is
particularly low (less than 0.3) in Australia and Austria. However, it is high in Turkey (3 per
100,000 children) and Mexico.
Globally, because there are great disparities according to the type of cancer, almost three –
quarters of childr en recover, twice as much as in the 80s. They then resume their course of life,
grow up and enter the workforce. In France, there are approximately 25,000 adults cured of
paediatric cancer.
While hopefully out of the woods, studies of patients treated 20 or 30 years ago show that
some of them have long -term sequelae. Cancer treatments can indeed have undesirable
consequences – or iatrogenic effects – sometimes several decades after healing. C hildren, who have
not finished growing and gone through puberty, are particularly exposed to it, especially since their
life expectancy greatly exceeds that of recovered adults. To identify the treatment methods and the
agents responsible, scientists const itute large cohorts such as FCCSS which will bring together
18,000 subjects cured of paediatric cancer before the year 2000.
Florent de Vathaire, researcher and epidemiologist at Inserm and the Gustave Roussy
Institute, is more particularly interested in t he effects of radiotherapy: „Children are more sensitive
than carcinogens and in particular to radiation, than adults. showed the studies carried out
following the bombings of Hiroshima and Nagasaki. However, during radiotherapy, even targeted,
the tissues surrounding the tumour are irradiated by several centimetres because of the body re –

diffuses. Because of their weak corpulence, children are more affected ” (de Vathaire, El -Fayech,
Ayed, et al., 2012:1002‐1010 )24.
The late effects of radiotherapy depend o n the doses used, the area treated and the proximity
of organs sensitive to radiation. Until very recently, toxic doses not to be exceeded were calculated
based on short -term side effects, which occur within a few years of treatment. The most recent
work h as identified other risks so that they are also taken into account.
The late effects of chemotherapy are more difficult to demonstrate because the treatments
are newer, more numerous and often combined or with radiotherapy.
However, the toxicity of certain drugs is well established. Paediatrician -oncologist at the
Curie Institute , Dr Hélène Pacquement notes that it is not a question of questioning the use of these
drugs which bring a net benefit in terms of healing. On the other hand, „better knowing their risks
allows a ” therapeutic de -escalation „which, gradually, leads to reser ving them for situations in
which they are really necessary and using the smallest effective doses ”. A situation which is also
observed in radiotherapy25.
Because they also damage healthy cells, cancer treatments can induce new cancer years
after the first illness. These secondary cancers are to be distinguished from late recurrences which,
even if they are rare, can still occur more than ten years after treatment. Overall, studies show that
chemotherapy and radiotherapy increase the risk of having secondary cancer in the same
proportions and that their effects add up if they are combined. In the latter case, one out of five
former patients are affected at the age of 40, almost one in two at 50 years old.
All tissues can be affected, but certain organs, such as the thyroid and breast, are
particularly sensitive to radiotherapy. Florent de Vathaire specifies: „Radio -induced thyroid cancer
occurs between 10 and 50 years after the end of treatment, justifying the long -term follow -up of
the people concerned. Breas t cancer also increases at low doses. For 2 or 3 grays (Gy) 8, the risk
is comparable to that found with the BRCA1 and 2 mutations. For very high doses, it is multiplied
by 10 or more ”.
Certain drugs, commonly used in chemotherapy, are associated with an i ncreased risk of
secondary leukaemia (class of alkylating agents, anthracyclines, etoposide …). Taking the example
of anthracyclines in the treatment of nephroblastoma, the most frequent renal tumour in children,
Dr Pacquement notes that they are no long er justified in less aggressive cancers (Nielsen, White,
Hong, 2016:231 -8.)26.

24 de Vathaire F, El -Fayech C, Ben Ayed FF, et al. Radiation dose to the pancreas and risk of diabetes mellitus in
childhood cancer survivors: a retrospective cohort study. Lancet Oncol. 2012;13(10):1002‐1010.
doi:10.1016/S1470 -2045(12)70323 -6
25 Idem.
26 Nielsen SM, White MG, Hong S, Aschebrook -Kilfoy B, Kaplan EL, Angelos P, Kulkarni SA, Olopade OI,
Grogan RH. The Breast -Thyroid Cancer Link: A Systematic Review and Meta -analysis. Cancer Epidemiol

Radiotherapy and chemotherapy can also weaken the heart and cause cardiovascular
pathologies (infarction, arrhythmia, valvular heart disease …). As in the case of secondary cancers,
high doses and combined treatments greatly increase the incidence of the se diseases. All treatments
and all pathologies combined, 20% of adults cured of paediatric cancer would be affected before
the age of 55 years old.
Thus, in chemotherapy, anthracyclines are known for their cardiac toxicity, in the short and
longer -term. T hey increase the risks from the first administration with a dose -dependent effect. Dr
Pacquement remarks: „The involvement can go unnoticed for a long time and then reveal itself
through certain events, such as pregnancy in women due to the cardiovascular changes caused ”.
Alkylating agents, such as busulfan, and vinca alkaloids also increase cardiovascular risks.
Former patients are advised to carry out regular cardiological check -ups.
Radiation therapy, when it affects the pituitary gland, the thyroid and / or the ovaries (very
rarely the testicles), as well as certain chemotherapies, can delay puberty and cause slower growth,
lower fertility, or even sterility … Again, it all depends on the doses used, the therapeutic protocol
and the age at the time of treatment (Chang, Okwuosa, Scarabelli, Moudgil, Yeh, 2017:2552 –
2565 )27.
Effects on fertility can be prevented in pubescent boys by collecting sperm before
treatment. Before puberty, the conservation of a gonad or part of the gonad (testicle or ovary),
remov ed surgically, gives hope for later fertility, even if advances are still necessary for terms of
research. Other therapeutic agents have little or no long -term consequences. However, women
wishing to have children are often advised not to wait too long. Some medications advance the age
of menopause by several years.
Cerebrovascular pathologies, by affecting the blood vessels, can be at the origin of
cerebrovascular accidents (strokes). They are mainly caused by radiation therapy when it affects
the brain.
Florent de Vathaire ’s team (de Vathaire, El -Fayech, Ayed, et al., 2012:1002‐1010)28
showed that the risk was linked to the irradiation of a particular area located at the base of the
brain: the polygon of Willis .

Biomarkers Prev. 2016 Feb;25(2):231 -8. doi: 10.1158/1055 -9965.EPI -15-0833. PMID: 26908594; PMCID:
PMC4770576.
27 Chang HM, Okwuosa TM, Scarabelli T, Moudgil R, Yeh ETH. Cardiovascular Complications of Cancer Therapy:
Best Practices in Diagnosis, Prevention, and Management: Part 2. J Am Coll Cardiol. 2017 Nov 14;70(20):2552 –
2565. doi: 10.1016/j.jacc.2017.09.1095. PMI D: 29145955; PMCID: PMC5825188.
28 de Vathaire F, El -Fayech C, Ben Ayed FF, et al. Radiation dose to the pancreas and risk of diabetes mellitus in
childhood cancer survivors: a retrospective cohort study. Lancet Oncol. 2012;13(10):1002‐1010.
doi:10.1016/S14 70-2045(12)70323 -6

Irradiation of other parts of the br ain, on the other hand, does not increase cerebrovascular
pathologies, „explains the researcher. Most chemotherapy does not seem to have an impact on the
risk of stroke either.
Surgery poses more difficulties (physical or sensory sequelae, learning disabil ities, lack of
attention, fatigability, disinhibition …). However, these are extremely variable, very dependent on
the affected brain area and the age of the child.
In 2012, Florent de Vathaire ’s team were the first 10 to show that irradiation of the pancreas
increases the risk of diabetes. This discovery made it possible to develop new recommendations
so that radiotherapists spare the pancreas as much as possible when they treat a tumour located
nearby (kidney cancer in particular).
Surgery and radiation therapy to the chest can decrease breathing capacity, as can certain
drugs have used in chemotherapy.
Doctors also note orthopaedic sequelae after surgery for bone tumours (uneven leg length,
etc.), a risk of scoliosis after extensiv e thoracic surgery, hearing problems in subjects treated with
cisplatin, risk of cataracts and tooth anomalies in children who received busulfan at a very young
age, sometimes chronic pain not sufficiently taken into account …
Finally, Dr Pacquement dra ws attention to the psychological repercussions which can also
occur years after recovery: „The disease has direct repercussions on the medical level, family
relationships and, more generally, how society considers you (obstacles to borrowing for
example). It can be difficult to live with, in particular for very young treated patients who do not
keep any conscious memories of this stage of their life „ (de Vathaire, El -Fayech, Ayed, et al.,
2012:1002‐1010) 29.
As the effects of paediatric cancer treatments a re better and better known, the major
oncology centres are setting up specialized consultations for people who have recovered. Recently,
the Gustave Roussy Institute thus recontacted more than 500 former patients treated before 1985.
Former patients must go to these follow -up consultations due to the fact the ordinary
practitioners, even if they are higher and better informed, comprehend little long -term sequelae of
cancer treatments . They may not make the connection during certain symptoms, „notes Florent de
Vathaire. This meeting allows you to obtain a precise summary of the history of the disease and
the treatments received as a child.
In the absence of an invitation, she advises the recovered adults to request an interview
themselves from the centre that treated them.

29 de Vathaire F, El -Fayech C, Ben Ayed FF, et al. Radiation dose to the pancreas and risk of diabetes mellitus in
childhood cancer survivors: a retrospective cohort study. Lancet Oncol. 2012;13(10):1002‐1010.
doi:10.1016/S1470 -2045(12)70 323-6.

Doctors also insist on the rules of healthy living (being physically active, not smoking, not
drinking alcohol, limiting sun exposure, etc.). The latter is all the more important to respect since
it seems, even if the data are still lacking to be affirmative, that for secondary cancers, cardiac and
cerebrovascular pathologies, as well as for diabetes, there is a multiplicative effect between risks
related to treatments and those related to lifestyle. „The good news is that people who have
recovered from paediatric cancer are generally more attentive to their health than the average
population, ” Florent de Vathaire stated .
Children currently being treated will be followed for the long term, for life if necessary,
depending on the treat ment received. But Dr Pacquement wants to be reassuring: „All of these late
effects of the treatments concern patients treated more than twenty years ago. Current treatments
are often different, sometimes less intensive in certain pathologies with very hig h cure rates so that
they are likely to have fewer long -term effects (Rodriguez -Galindo, Friedrich, Alcasabas, Antillon,
Banavali, Castills, Israels, Jeha, Harif, Sullivan, Quah, Patte, Pui, Barr, Gross, 2015 3065 -73)30„.

30 Rodriguez -Galindo C, Friedrich P, Alcasabas P, Antillon F, Banavali S, Castillo L, Israels T, Jeha S, Harif M,
Sullivan MJ, Quah TC, Patte C, Pui CH, Barr R, Gross T. Toward the Cure of All Children with Cancer Through
Collaborative Efforts: Pedi atric Oncology as a Global Challenge. J Clin Oncol. 2015 Sep 20;33(27):3065 -73. doi:
10.1200/JCO.2014.60.6376. Epub 2015 Aug 24. PMID: 26304881; PMCID: PMC4979198.

Conclusions – life after leukaemia

During treatment for childhood leukaemia , the main concerns for most families are the
daily aspects that are aimed at ending all treatment and overcoming leukaemia . After completing
treatment, concerns tend to be directed to the long -term effects of leukaemia and its treatment, as
well as the re turn of leukaemia .
It is certainly normal to want to forget leukaemia and its treatment and return to a life that
does not revolve around cancer. However, it is important to understand that follow -up care is a
central part of this process that offers your child the best chance for recovery and long -term
survival. For several years after treatment ends, regular follow -up exams will be very important.
Doctors will monitor for possible signs of leukaemia and side effects in the short and long term of
treatment .
Medical check -ups typically include thorough physical exams and lab tests, and sometimes
imaging tests. The schedule for these reviews will depend on the type and subtype of leukaemia ,
the treatment given, and other factors. Reviews will usually be done every month for the first year,
and then less frequently for at least 5 years after therapy. After that period, most children visit their
doctors at least every year for a medical review.
For the most common types of childhood leukaemia (ALL and AML), if t he leukaemia
returns, it will be more often while the child is still receiving treatment or within about a year of
completing treatment. Recurrence of ALL or AML is unusual if there are no signs of the disease
within the next 2 years.
One benefit of follow -up medical visits is that it allows you to discuss questions and
concerns that may arise during and after your child ’s recovery. For example, almost all cancer
treatments have side effects. Some disappear shortly after treatment, but others can last a lon g
time, or may even appear up to years later. It is important that you immediately report any new
symptoms to your doctor so that their cause can be found and treated, if necessary.
Even if you want to forget your experience as much as possible after treat ment ends, during
this time you must keep important reports of your child ’s medical care. Collecting these details
shortly after treatment may be easier than trying to obtain them in the future. This can be very
helpful later if you (or your child) change doctors (Ness, Armenian, Kadan -Lottick, Gurney,
2011:185 -97)31.

31 Ness KK, Armenian SH, Kadan -Lottick N, Gurney JG. Adverse effects of treatment in childhoo d acute
lymphoblastic leukaemia: general overview and implications for long -term cardiac health. Expert Rev Hematol.
2011 Apr;4(2):185 -97. doi: 10.1586/ehm.11.8. PMID: 21495928; PMCID: PMC3125981.

Maintaining health insurance coverage is also very important. Studies and medical
consultations are expensive, and although no one wants to think about the return of cancer, this
could happen. Thanks to significant medical advances, most children who have received treatment
for leukaemia now live to adulthood. Therefore, their health as they become adults has become a
matter of care in recent years.
Just as treating leukaemia in children requires a very specialized approach, so does care
and follow -up after treatment. The earlier problems are recognized, the more likely they are to be
able to treat them effectively.
Childhood leukaemia survivors are at risk, to some degree, for several possible late effects
in their treatments. This risk depends on several factors, such as the type and subtype of leukaemia ,
the type and doses of the treatments they received, and the age of the child at the time of receiving
the treatment. It is important to talk to the team of health professionals caring for your child about
the possible effects that may occur so that you can watch for them and notify the doctor.
Children who have been treated with leuka emia are often at increased risk of developing
other cancers later. One of the most serious possible side effects of therapy for acute lymphocytic
leukaemia (ALL) is a small risk of later acute myeloid leukaemia (AML).
This occurs in a small percentage of patients after receiving certain chemotherapy drugs,
such as epipodophyllotoxins (etoposide, teniposide), alkylating agents (cyclophosphamide,
chlorambucil), or anthracyclines (daunomycin, doxorubicin). Of course, the risk of these second
cancers must be w eighed against the obvious benefit of treating a life -threatening disease like
leukaemia (Harrington, Smith, 2008:2667 -78.)32. Certain chemotherapy medicine or radiations
took to the chest can now and again cause heart or lung problems later in life . The ri sks of heart
disease and stroke are higher among children treated for ALL. Therefore, close monitoring is very
important.
Treatment that includes radiation therapy to the brain or some types of chemotherapy can
affect learning ability in some children. Due to this, professionals try to reduce treatments that
could cause damage to the brain (including radiation) as much as possible.
Some cancer treatments can affect a child ’s growth, and their height may be slightly smaller
as adults. This is particularly true after stem cell transplants. If necessary, the problem can be
addressed by treating survivors with growth hormone. Treatment can also affect the levels of other
hormones in the body, which can increase the risk of health problems, such as thyroid problems,
obesity, and diabetes.

32 Harrington SE, Smith TJ. The role of chemotherapy at the end of life: „when is enough, enough?”. JAMA. 2008
Jun 11;299(22):2667 -78. doi: 10.1001/jama.299.22.2667. PMID: 18544726; PMCID: PMC3099412.

Cancer treatment may also affect sexual development and the ability to have children in
the future. Talk to your child ’s team of cancer professionals about the infertility risks that can
come with treatment. Also a sk if there are options to preserve fertility, such as sperm banks. For
more information, see How to preserve fertility in children and teens with cancer.
The use of prednisone, dexamethasone, or other steroids can cause bone damage or
osteoporosis (brittl e bones). There may also be other possible complications from chemotherapy
or other treatments. Your child ’s doctor should carefully review any possible problems with you
before starting your child ’s treatment.
To help increase awareness of late effects an d improve follow -up care for childhood cancer
survivors throughout their lives, the Children ’s Oncology Group has developed long -term follow –
up guidelines for these survivors. These guides can help you know what to pay attention to, what
types of screening tests should be done, and how late effects can be treated.
It is very important to discuss possible long -term complications with the health
professionals caring for your child and to make sure that there is a plan in place to keep an eye on
these problems and treat them, if necessary. To learn more, ask your child ’s doctor about the
Children ’s Oncology Group Survivor Guidelines which were written by health professionals.
Patient versions of some of the guides are also available (such as Health Links) on th e website.
We encourage you to review these guidelines with your doctor (or more information about the
possible effects of long -term treatment, see Late effects of childhood cancer treatment).
Social and emotional problems can arise during and after treatm ent. Factors such as the
child ’s age at diagnosis and the extent of treatment may play a role in this matter.
Some children may have emotional or psychological problems that require attention during
and after treatment. Depending on age, they may also have some problems with their normal
performance and at school. Often support and encouragement can help deal with these problems.
Doctors and other members of the health care team can often recommend some special support
programs and services to help children after treatment. Many experts recommend that school -age
children attend school as much as possible. By doing this, they can maintain a sense of normal life
and keep their friends informed about what is going on.
Parents , friends and other family members c an also be affected, both emotionally and in
other ways. Some common family concerns during treatment include financial hardship,
transportation to the cancer centre and accommodation near the cancer centre , the need to be absent
from work, and the need fo r homeschooling. In cancer centres , social workers and other
professionals can assist family members with these issues.

Centres treating many leukaemia patients may offer programs for new patients and their
families to meet others who have finished treatme nt. This can give you an idea of what to expect
during and after treatment, it can be very important.
After treatment ends, various emotional concerns may arise. Some of these concerns can
last a long time and may include dealing with physical changes that may arise as part of treatment ,
concerns about the return of leukaemia or the emergence of new health problems , feelings of
resentment for having had leukaemia or going through treatment when others have not had to go
through this , concerns ab out being treated differently or being discriminated against (by friends,
classmates, co-workers , employers, etc.) , concerns about dating, getting married and having a
family in the future33.
No one chooses to have leukaemia , but for many survivors of child hood leukaemia , the
experience can be positive over time, allowing solid values to be established. Other survivors may
have a more difficult recovery period to adjust to life after cancer and get on with their lives. It is
normal to feel some anxiety or ot her emotional reactions after treatment, but feeling overly
worried, depressed, and upset can affect many aspects of a young person ’s growth. This can affect
the way you relate to others, school, work, and other aspects of life. With the support of family,
friends, other survivors, mental health professionals, among others, many people who have
survived leukaemia can get ahead despite the challenges they have faced.

33 https://www.cancer.org/cancer/leukemia -in-children/after -treatment/follow -up.html

Research
Quality of life in pediatric patients with acute lymphoblastic leukaemia

As mentioned before, acute lymphoblastic leukaemia is a malignant neoplasm
characterized by a cytogenetic alteration that causes abnormal monoclonal proliferation of
precursor cells of the lymphoid series and that infiltrates more than 25% of the bone marrow. It is
the most frequent malignancy in children and represents 25% of all types of cancer in children.
Leukaemia treatment consists of four periods: induction to remission, intensification,
consolidation and maintenance; and its global duration is approximately three years.
Survival in children with cancer has improved significantly in recent years. This has been
attributed to the organization of specialized centres with multidisciplinary teams and the
development of programs bas ed on numerous clinical trials; Especially in children with acute
lymphoblastic leukaemia, great progress has been made due to a better understanding of its
pathophysiology, the development of new chemotherapy agents and the improvement of
supportive care for patients. Currently, the survival rate for patients with acute lymphoblastic
leukaemia exceeds 80%.
In 1948, the World Health Organization (WHO) defined health as complete physical,
mental, and social well -being, and not just as the absence of disease. This concept has evolved to
that of quality of life, which includes a state of functional health, perception of good health,
satisfaction with life and ability to compete. Both the general perception of health and vitality,
pain and disability can be infl uenced by a person's personal experiences and expectations; that is
why the concept of quality of life requires a valid and reliable evaluation method, which involves
the evaluated person. Currently, some questionnaires include different versions for each age group
that ask about symptoms that occurred in the patient in the last month and in the last seven days to
assess the quality of life of the cancer patient.
PedsQL ©, in its version for cancer patients (PedsQL Cancer Module ©), is a
multidimensional mo del that contains scales that assess physical, emotional, social and school
functioning. There are numerous advantages of this model, such as its brevity (few reagents unlike
other models), it is practical (four minutes to answer it), flexible (designed to be applied in the
community, school, and clinical practice),
Appropriate for each age group (modules 2 -4, 5-7, 8-12 and 13 -18 years), multidimensional
(evaluates physical, emotional, social and school status), reliable (internal consistency of 0.88 in
the report of children and 0.90 in that of parents) and valid (distinguishes between healthy children
and those with acute and chronic diseases); Also, it distinguishes the severity of the disease within
a chronic condition.

PedsQL Cancer Module 3.0 © is the latest version of the applicable model for cancer
patients, including more variables to assess the quality of life in this type of patient. This model is
also multidimensional and evaluates eight scales: pain and discomfort, presence of nausea, anxiety
from procedures, anxiety from treatments, worries, cognitive problems, perception of physical
appearance and communication.
During treatment, most children experience adverse effects, not only physical but also
emotional; especially since it is a chronic tre atment. The most important is pain, lack of energy to
enjoy the activities of daily life and fear of the future. In addition to the effects on the child, parents
also experience feelings such as depression and anxiety, especially during the first months af ter
the disease is diagnosed, even more so when they accompany their child to the hospital, missing
work and trying to understand medical management. your child's home.
Because many of the components of quality of life cannot be directly observed, they are
evaluated through questionnaires that contain a series of questions and assign a final score that is
interpreted according to previously established values. In recent years, quality of life studies has
been conducted in pediatric cancer patients, but most of them focused on survivors and terminally
ill patients. Few studies have been conducted during the treatment phase of the disease. In these
last studies, it has been seen that the quality of life is lower in patients with active treatment than
in those survivors who have finished treatment.
Optimal treatment of the child with acute lymphoblastic leukaemia requires care in several
areas of supportive care, including transfusions, infectious complications, metabolic and
nutritional needs, and continuous an d comprehensive psychosocial support for the patient and
family. Supportive care refers to a treatment designed to prevent and control the adverse effects of
cancer and its treatment. These effects not only cause discomfort to the patient but can interfere
with the correct administration and planning of chemotherapy. To achieve an optimal therapeutic
goal and improve quality of life, these adverse effects must be managed appropriately.
Currently, there is a tendency to evaluate a person beyond his physical capacity and takes
into account his social context, level of self -esteem, mental health and social supports. Although
the terms “state of health”, “state
Functional "and" health -related to quality of life "have been used interchangeably, a
distinction must be made between these terms, since the first two refer only to the physical state
of the patient, while the term associated with quality of life is referred to the patient's perception
of the impact of their disease and treatment in various aspects of lif e: physical, emotional, social,
functional role, etc.
The measurement of quality of life in pediatric patients must be carried out using a
multidimensional model, and at the same time adapted to the age group such as the Peds -QL

Cancer Module ©. The PedsQL © and the PedsQL Cancer Module © have been used to as sess QoL
in children with different nosologically entities.
During a multicenter study, Varni et al (2001 :800‐812 )34 evaluated the reliability and
validity of the PedsQL Cancer Module © applying it to 339 children aged 2 -18 years with cancer
(50% with LAL), who were in treatment and remission of the disease, compared to a group of
healthy children; the questionnaire was able to identify the healthy children of the sick, and of
those who were in treatment versus those who had no treatment.
In another study, published in April 2008, three quality of life measurement scales
(Pediatric Quality of Life Inventory -PedsQL -, Child's Health Questionnaire -CHQ -, and Health
Utilities Index -HUI) were compared in children with cancer (62 % with LAL) during
chemotherapy tre atment. Weekly measurements were made during the first four weeks from the
third day of diagnosis, and it was found that PedsQL © was the one with the highest sensitivity to
detect changes in quality of life in patients.
The probability of survival of chil dren with acute lymphoblastic leukaemia has improved
significantly, currently obtaining more than 75% cure. Cancer treatment involves a combination
of chemotherapy, radiotherapy and surgery, with a high level of aggressiveness, which when
applied to a chil d, whose being is growing, invades its development, alters it and causes an impact
on a physical and psychological level, being able leaving sequelae that become evident even late,
thus affecting their quality of life.
As the number of children cured of ca ncer increases, the need to evaluate the impact that
the disease has had on their quality of life is generated, understanding by this the level of well –
being derived from the evaluation that the minor carries out from various domains of his life,
consideri ng the impact they have on your health.
To know the quality of life of the Honduran population, at the Hospital Nacional Dr Mario
Catarino Rivas the population studied gave a perspective on the quality of life of the patient with
acute lymphoblastic leukae mia and what to expect from the survival of the patient. This helped to
generate protocols in the hospital environment to improve the quality of life of the patient.
The specific goals were to know the sociodemographic data of patients diagnosed with
acute lymphoblastic leukaemia; to determine the quality of life scores in the physical, emotional,
intellectual and social skills aspects; to identify which is the dimension of quality of life most
affected; to determine the quality of life in the different pha ses of treatment
The main questions to be answered were:

34 Varna JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Paediatric Quality of Life Inventory
version 4.0 generic core scales in healthy and patient popula tions. Med Care . 2001;39(8). doi:10.1097/00005650 –
200108000 -00006.

1. What sociodemographic characteristics do the patients who come to the Hospital
Nacional Dr Mario Catarino Rivas with a diagnosis of acute lymphoblastic leukaemia have?
2. What is the quality of li fe like in patients with acute lymphoblastic leukaemia in terms
of physical, emotional, intellectual, and social skills?
3. What is the dimension of quality of life most affected?
4. What is the quality of life like in the different phases of chemotherapy treatment in
patients with ALL?
Let us remind ourselves, leukaemia represents 25 -30% of malignancies in children under
14 years of age, being the most frequent cancer in childhood. More than 95% of childhood
leukaemias are acute, and acute lymphoblastic l eukaemia (ALL) predominates among these
(Bernal MG, Serra IB, 2012:1 –7.).35 Although the aetiology is unknown, some genetic, viral, and
environmental predisposing factors have been described. The clinical manifestations are usually
the consequence of the oc cupation of the bone marrow by the leukemic cells (anaemia,
thrombocytopenia and neutropenia) (Lassaletta Atienza A., 2016:380 –9)36.
Childhood acute lymphoblastic leukaemia, also called acute lymphocytic leukaemia
(ALL), is a disease characterized by a diso rderly proliferation of immature lymphoid line cells
(blasts) arising from the stem cell in the bone marrow. The disordered growth of white blood cells
in the bone marrow blocks the normal development of red blood cells and platelets (idem, Lla L.
Leucemia , 2014:83 –116)37. The stem cell develops two different types of white blood cells:
lymphocytes and neutrophils. There are two types of lymphocytes: T lymphocytes and B
Lymphocyte.
The four main types of leukaemia are acute lymphocytic. (LLA), acute myelocyt ic (AML),
chronic lymphocytic (LLC), chronic myelocytic. (LMC).
Disordered blast proliferation in the bone marrow can extend the presence of blasts in the
blood, lymph nodes, spleen, liver, central nervous system, testes, or other organs. Acute
lymphoblast ic leukaemia is the most common malignancy in children, accounting for 25% of all
childhood cancers and approximately 75% of all childhood leukaemia cases (ibidem)38.
The incidence rate of childhood leukaemia in Spain, Europe is 4 cases / 100,000 in <14
years old (Lassaletta Atienza A., 2016:380 –9)39. Each year in western countries between 60 and
100 new cases of leukaemia appear for every million inhabitants. Leukaemia is the most common

35 Bernal MG, Serra IB. Leucemia en la infancia: Signos de alerta. An Pediatr Contin. 2012;10(1).
36 Lassaletta Atienza A. Leucemias. Leucemia linfobl??stica aguda. Pediatr Integr. 2016;20(6) .
37 Idem and Lla L. Leucemia linfoblástica aguda. 2014.
38 Ibidem.
39 Lassaletta Atienza A. Leucemias. Leucemia linfobl??stica aguda. Pediatr Integr. 2016;20(6).

cancer in children and adolescents, accounting for about a third of al l cancer cases in children
under the age of 15 and a quarter of cancer cases occurring before the age of 20.
It was estimated that in 2013, about 6,070 new cases of ALL would be diagnosed in the
United States. According to the most recent data, it is estim ated that 66,030 people live with ALL
or are in remission of the disease (Lla L., 2014:83 –116)40.
Acute lymphocytic leukaemia is more common in early childhood, reaching its highest
incidence between the ages of 2 to 3 years (> 80 per million per year), wi th rates decreasing to 20
per million among children aged 8 to 10 years. age. The incidence of ALL in patients 2 to 3 years
of age is approximately 4 times higher than among children younger than 2 years and almost 10
times higher than among those 19 years of age (idem and Popular S.,2014:1 –5)41. Acute
lymphocytic leukaemia is slightly more common in white boys than in black and Asian boys, and
in boys than in girls (Popular S. ,2014:1 –5)42.
Among the prognostic factors is age, patients younger than one year and older than 10 years
are considered high -risk patients, so in these age groups, the execution of more aggressive
treatment is considered to obtain more favourable results, pediatric patients in the age group
between 1 and 9 years have a better prognosi s.
Gender is also a prognostic factor of consideration; female patients have a better prognosis
than male patients, this is due in part to the appearance of testicular relapses that may present with
an increased risk of relapse, due to factors that are not fully understood, it has been described that
Afro -descendant or Hispanic pediatric patients diagnosed with ALL have a lower cure rate than
children of other races.
Patients who have a high total white blood cell count are classified as high -risk cases and
generally require more intensive treatment; since a count of 50,000 cells / mm3 is a cut -off point
between a better or worse prognosis due to the relationship between the high number of white
blood cells in the blood and other high -risk prognostic factors , such as chromosomal translocations
(H.L. Ocana -Servín A, Tlatoa -Ramírez HM. 2015:116 –22)43.
Certain genetic diseases cause children to be born with an abnormal or poor immune
system. In addition to the spread of serious infections due to low immune defen ces, these children
also have a greater tendency to contract leukaemia.
– Li-Fraumeni syndrome. It is a rare condition that increases a person's risk of developing
leukaemia, bone or soft tissue sarcomas, breast (breast) cancer, and brain tumours.

40 Lla L. Leucemia linfoblástica aguda. 2014.
41 Idem and Popular S. Protocolo de la atención par a leucemia linfoblástica. Guía clinica y esquema de tratamiento.
Igarss 2014. 20141 –5.
42 Popular S. Protocolo de la atención para leucemia linfoblástica. Guía clinica y esquema de tratamiento. Igarss
2014. 2014;(1).
43 H.L. Ocana -Servín A, Tlatoa -Ramírez HM. Medicina e Investigación. Med e Investig. 2015;3(2).

– Down syndrome. These children are at increased risk of getting leukaemia, 15 times more
likely than other children. The syndrome is also associated with a leukaemia -like illness within the
first month of life, which can resolve on its own without using che motherapy. There is a
cumulative risk of developing leukaemia of 2.1% by age 5.
The environmental risk factors are Radiation and exposure to chemical products. Serious
radiation injury is a major environmental risk factor for childhood leukaemia. Japanese atomic
bomb survivors had a 20 -fold increased risk of acquiring acute myelogenous leukaemia, usually
within 6 to 8 years after exposure. Prenatal X -ray exposure, exposing the fetus to intense radiation
within the first few months of development can also ca rry up to the 5 -fold increased risk of
acquiring acute lymphocytic leukaemia (H.L. Ocana -Servín A, Tlatoa -Ramírez HM. 2015:116 –
22)44.
On the other hand, patients who have been treated with radiotherapy and chemotherapy for
other types of cancer have a slig ht risk of contracting second cancer, generally acute myelogenous
leukaemia, later in life, e.g.: alkylating agents such as cyclophosphamide and
epipodophyllotoxins). These leukaemias generally originate within the first 5 to 8 years after
treatment and te nd to be difficult to treat. Patients who receive intensive treatment to suppress their
immune function (especially organ transplant patients) are at increased risk for cancer, especially
of the lymphoid system.
1. Weight> 4000 g. at birth
2. Maternal age> 35 years
3. Paternal age> 40 years
4. Maternal history of fetal loss
5. Exposure to ionizing radiation in utero and postnatal
6. Direct exposure to hydrocarbons and pesticides
7. Alcoholism during pregnancy
8. Smoking during pregnancy (Velásquez H, Rivera SV,2015:110 –5.)45
The clinical picture of leukaemia depends on the one hand on the medullary infiltration by
the leucoblasts or blasts, which prevents normal haematopoiesis, and on the other hand, on the
extramedullary extension of the disease.
It is usual for the presentation to follow an insidious, subacute course, although it is
sometimes diagnosed as a result of an urgent complication. The toxic picture with asthenia and
anorexia is relatively frequent, but not significant weight loss. Symptomatic anaem ia will generally
manifest as pallor, asthenia, and tachycardia, but in severe cases, it can cause tinnitus, headache,

44 H.L. Ocana -Servín A, Tlatoa -Ram írez HM. Medicina e Investigación. Med e Investig. 2015;3(2).
45 Velásquez H, Rivera SV., Early diagnosis of acute leukaemia in children and adolescents. 2015;54(2):110 –5.

vertigo, dyspnoea, and heart failure (Marwaha RK, Kulkarni KP, Bansal D, Trehan A, 2010:249 –
54.)46.
Fever is the most frequent reason for consultation in paediatrics and is present in around a
third of childhood leukaemia cases. A feverish condition of more than 2 weeks duration associated
with the presence of lymphadenopathy, hepatomegaly and / or splenomegaly, asthenia, anorexia
and bone pain should increase the suspicion of leukaemia in the paediatrician. The finding of fever
in leukaemia may be due to the tumour itself due to the release of pyrogenic substances from the
blasts, but it always forces us to rule out the concomitant presence of associated infections.
The presence of haemorrhages in the form of petechiae, bruising, epistaxis or another less
frequent bleeding usually translates a certain degree of thrombocytopenia or coagulation disorders,
the latter more frequent in certain ty pes of AML (idem)47.
Bone and / or joint pain is present in 27 -33% of pediatric leukaemia’s. It is generalized
pain, which can manifest as lameness, functional impotence, or rejection of ambulation. Habitually
it is associated with elevation of the acute p hase reactants (lactic dehydrogenase [LDH],
rate of globular sedimentation [ESR], C -reactive protein [PCR]) and fever, which is why it raises
the differential diagnosis with juvenile idiopathic arthritis and other connective diseases. The
association with leukopenia or thrombocytopenia, as well as the presence of osteoarticular pain
that awakens the patient at night, are more indicative of leukaemia.
It would lie in the infiltration of the bone marrow and the periosteum, periosteal insufflation
due to under lying cortical injury or the presence of bone heart attacks (ibidem)48.
Blasts can theoretically invade any tissue in the body, as has been observed in autopsy
studies. Extramedullary infiltration is somewhat more common in AML than in ALL (Vardiman
JW, Th iele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al., 2009. p. 937 –51.)49.
1. Hepatomegaly and/or splenomegaly is present at diagnosis in between one and two –
thirds of patients and can be massive.
2. A mediastinal mass may be present on chest radio graphy in 10% of ALL, especially in
T-type.

46 Marwaha RK, Kulkarni KP, Bansal D, Trehan A. Acute lymphoblastic leukaemia masque rading as juvenile
rheumatoid arthritis: Diagnostic pitfall and association with survival. Ann Hematol. 2010;89(3):249 –54.
47 Idem.
48 Ibidem.
49 Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World
Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia: Rationale and important
changes. Vol. 114, Blood. 2009. p. 937 –51.

3. Lymphadenopathies can be found in 10 -20% of childhood leukaemia’s, are firm in
consistency and are not usually associated with pain or other inflammatory signs (Vardiman JW,
Thiele J, Arber DA, Brunning RD, Bo rowitz MJ, Porwit A, et al., 2009. p. 937 –51.)50.
4. Testicular involvement.
5. Involvement of the central nervous system (CNS) is present in less than 5% of cases,
although Symptoms are rarely evident.
6. Renal involvement: it is a unilateral or bilateral nephromegaly detected by ultrasound at
the diagnosis of leukaemia. There is usually no associated with arterial hypertension.
Bone and / or joint pain is present in 27 -33% of pediatric leukaemia's. It is generalized
pain, which can manifest as lameness, fu nctional impotence, or rejection of ambulation.
Habitually, it is associated with elevation of the acute phase reactants (lactic dehydrogenase
[LDH], rate of globular sedimentation [ESR], C -reactive protein [PCR]) and fever, which is why
it raises the diff erential diagnosis with juvenile idiopathic arthritis and other connective diseases.
The association with leukopenia or thrombocytopenia, as well as the presence of osteoarticular
pain that awakens the patient at night, are more indicative of leukaemia. It would lie in the
infiltration of the bone marrow and the periosteum, periosteal insufflation due to underlying
cortical injury or the presence of bone infarcts.
Extramedullary leukaemia
Blasts can theoretically invade any tissue in the body, as has been observed in autopsy
studies. Extramedullary infiltration is somewhat more common in AML than in ALL (idem)51.
1. Hepatomegaly and/or splenomegaly is present at diagnosis in between one and two –
thirds of patients and can be massive.
2. A mediastinal mas s may be present on chest radiography in 10% of ALL, especially in
T-type.
3. Lymphadenopathies can be found in 10 -20% of childhood leukaemia’s, are firm in
consistency and are not usually associated with pain or other inflammatory signs (ibidem)52.
4. Test icular involvement.
5. Involvement of the central nervous system (CNS) is present in less than 5% of cases,
although Symptoms are rarely evident.
6. Renal involvement: it is a unilateral or bilateral nephromegaly detected by ultrasound at
the diagnosis of leukaemia. There is usually no associated with arterial hypertension.

50 Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World
Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia: Rationale and important
changes. Vol. 114, Blood. 2009. p. 937 –51.
51 Idem.
52 Ibidem.

7. Skin involvement: Occasionally, the presence of neutropenia conditions the appearance
of skin infections by opportunistic germs, such as the case of the gangrenous ecthyma due to
Pseu domonas spp.
8. Other locations: can be found
Tumour cells infiltrating the optic nerve and other ocular regions, in the gastrointestinal
system, in the heart, lung or ovaries, among others (Meadows AT., 2012:1921 –2)53.
Most of the symptoms of leukaemia are not unique. Some of these symptoms can also be
caused by other problems, such as infections. For these reasons, an accurate diagnosis is needed,
and the best way to do this is to take samples of your child's blood and bone marrow.
Now, let us recap the process in the laboratory.
Blood count: Blood count may be normal at the initial stage of presentation of leukaemia.
During evolution, cytopenia may appear isolated (anaemia, neutropenia or thrombocytopenia) or
combined (bi -cytopenia or pancyto penia). Anaemia is usually normocytic, normochromic with
low reticulocytes. Leukocytes can range from normal to severe leukopenia values to
hyperleukocytosis. The platelet count may be normal or severe thrombocytopenia (Velásquez H,
Rivera SV., 2015:110 –5.)54.
Myelogram
The definitive diagnosis and typing of leukaemia are made with the myelogram or bone
marrow aspirate. This sample should be analysed with:
1. Conventional microscopy: can show normal or increased cellularity, composed of a
population of 80 % or more blasts with decreased or absent megakaryocytes. <5% immature cells
can be found in a normal medulla (more than 25% are required to diagnose leukaemia).
2. Flow Cytometry: with the use of Cytometry it is possible to define if the analysed
leukemic cells are of lymphoid or myeloid lineage and also if they express surface antigens. In
Lymphoblastic leukaemia, in addition to CD 45 (common leukocyte) and CD34 (very immature
hematopoietic precursors), TdT, CD1O (common antigen), CD79a, CD19 (line B), CD 3 and CD7
(line T) are also expressed. In myeloid leukaemia CD117 (immature myeloid precursor cells),
CD33 (unspecific myeloid and monoid antigen), CD15 (Neutrophils), CD14 (Monocytes)
Velásquez H, Rivera SV., 2015:110 –5.)55.
3. Cytogenetic study: it consi sts of the analysis of chromosomes and their structural or
numerical alterations. Recognition of these translocations helps identify certain types of acute

53 Meadows AT. Book Review Principles and Practice of Paediatric Oncology Fourth edition. E dited by Philip A.
Pizzo and David G. Poplack. 1692 pp., illustrated. Philadelphia, Lippincott Williams &amp; Wilkins, 2001. $239. 0 –
7817 -2658 -1. N Engl J Med [Internet]. 2012;346(24):1921 –2. Available at:
http://www.nejm.org/doi/abs/10.1056/NEJM2002061334 62423
54 Velásquez H, Rivera SV., Early diagnosis of acute leukaemia in children and adolescents. 2015;54(2):110 –5.
55 Velásquez H, Rivera SV., Early diagnosis of acute leukaemia in children and adolescents. 2015;54(2):110 –5.

lymphocytic leukaemia and acute myelogenous leukaemia and is important in determining
prognosis. Som e types of leukaemia have an abnormal number of chromosomes. For instance ,
acute lymphocytic leukaemia cells with more than 50 chromosomes are more sensitive to
chemotherapy, and those with less than 46 are more resistant) (idem)56.
At this time, there are no special tests recommended for early detection of leukaemia. The
best strategy for early diagnosis is prompt attention to the signs and symptoms of this disease.
Careful follow -up of children with known genetic abnormalities that may increase their
risk of developing leukaemia, those who have been treated for other cancers with chemotherapy,
or combination chemotherapy and radiation therapy, and those who have had transplants is
important. organs and are taking medications that suppress the immune system (Keever MAV,
Gómez JA, Núñez AE, Rojas JB.,2012:175 –89)57.
Leukaemia is not classified as most types of cancer, leukaemia affects the marrow of most
of the bones in the body, and leukemic cells are circulating throughout the body through the
bloodstream. In many cases, some leukemic cells have begun to accumulate in organs, such as the
liver, spleen, lymph nodes, testes, and the central nervous system (Popular S.,2014:1 –5)58.
In general, two factors are observed that are related to prognosis and are consist ent for the
different authors: age at the time of disease presentation and sex. Thus, patients between the ages
of 1 and 9 and female are less likely to die. Socioeconomic conditions seem to have some effect
on mortality (Keever MAV, Gómez JA, Núñez AE, Ro jas JB.,2012:175 –89)59.
Children with acute lymphocytic leukaemia are classified into two risk groups as high risk
and standard risk.
Among the clinical and laboratory indicators at the time of diagnosis related to the results,
we have the following:
• Age. Children younger than one year and children older than 10 years are considered high –
risk patients, therefore more aggressive treatment is used to improve the results. Children
from 1 to 9 years old have a more favourable result.
• Gender. Girls are more likely to heal than boys; This is due in part to episodes of testicular
relapse, and children are also at increased risk for relapse into the bone marrow due to
factors that are not fully understood.

56 Idem.
57 Keever MAV, Gómez JA, Núñez AE, Rojas JB. Metaanálisis sobre los factores pronóstico relacionados con la
mortalidad en niños con leucemia linfoblástica aguda. Bol Med Hosp Infant Mex. 2012;69(3):175 –89.
58 Popular S. Protocolo de la atención para leucemia linfoblástica. Guía clinica y esquema de tratamiento. Igarss
2014. 2014;(1):1 –5.
59 Keever MAV, Gómez JA, Núñez AE, Rojas JB. Metaanálisis sobre los factores pronóstico relacionados con la
mortalidad en niños con leucemia linfoblástica aguda. Bol Med Hosp Infant Mex. 2012;69(3):175 –89

• Race. Black children and Hispanic children with acute ly mphocytic leukaemia have a lower
cure rate than children of other races, the reasons for which are unknown but cannot be
explained based on known prognostic factors.
• White blood cell level. Patients with high counts are classified as high risk and generall y
need more intensive treatment. A count of 50,000 cells per mm3 is generally used as the
operational threshold between a better or worse prognosis.
• Cell morphology. For the morphological study, the criteria of the Franco -American -British
morphology (FAB) are taken into account, which classifies ALL as L1, L2 and L3 based
on the morphological characteristics of the leukemic cell, between 70 and 85% of pediatric
patients have L1 ALL.
• Immunophenotype of leukemic cells. It is based on identifying the affected lymphocyte
line, that is, T or B lymphocytes. It is the most important criterion, together with the
characterization of chromosomal abnormalities in predicting response to treatment.
Children with acute pre -B or early B -cell leukaemia react better than th ose with mature T –
cell or B -cell leukaemia.
• Cytogenetics: Patients are more likely to heal if their leukaemia cells have a larger number
of chromosomes (hyper diploids), especially if there is an additional chromosome 4, 10,
17, and 18. Children whose leuk aemia cells have fewer chromosomes (hypodiploid) are
less likely to heal. Children with a translocation between chromosomes 12 and 21 are also
more likely to be cured. Children with a translocation between chromosomes 9 and 22, or
between chromosomes 1 and 19, have a lower cure rate. Children with a translocation
involving chromosomes 4 and 11 or all q23 translocations also have a lower cure rate.
• Chromosomal shifts. they can be detected in a substantial number of pediatric ALL cases,
and some of these shif ts as described below are of prognostic significance. TEL -AML1 (t
(12; 21) cryptic shift): The fusion of the TEL (ETV6) gene on chromosome 12, to the
AML1 (CBFA2) gene on chromosome 21 can be detected in 20 to 25% of cases of
precursor B ALL, but rarely ob served in T -cell ALL. Children with cryptic t shift resulting
in TEL -AML1 fusion are generally 2 to 9 years old (Bobadilla -morales L, 2016:28)60.
• The Philadelphia chromosome. t (9; 22) is present in approximately 4% of pediatric ALL
and confers an unfavoura ble prognosis, especially when it is related to either a high GB
count or a slow initial response when starting therapy.
Displacement related to the MLL gene (11q23) occurs in about 6% of children with cases
of pediatric ALL, and are generally linked to an increased risk of not responding to treatment. If

60 Bobadilla -morales L, Corona -rivera JR, Corona -rivera A. Impacto del gen de fusion ETV6/Runx1 en leucemia
linfoblastica. 2016.

the leukemic cells are found in the cerebrospinal fluid or if the testicles are enlarged due to the
accumulation of leukemic cells, the probability of cure is lower (Keever MAV, Gómez JA, Núñez
AE, Rojas J B.,2012:175 –89)61.
The speed with which leukemic cells are killed after treatment has started is also related to
treatment. Various ways of evaluating the way leukemic cells respond to treatment have been used,
including:
The Bone Marrow Response on the S eventh and Fourteenth Day: Patients with a rapid
reduction of leukemic cells in their bone marrow within 7 or 14 days after starting multidrug
chemotherapy have a more favourable prognosis than patients who Leukemic cells are disposed
of from the bone marr ow more slowly.
Peripheral Blood Response to Steroid Pre -phase: Patients with a reduced blast count of less
than 1000 / mm3 after a 7 -day induction preface with prednisone and a dose of intrathecal
methotrexate (good response to prednisone) have a prognosi s. more favourable than patients
whose peripheral blast count remains above 1000 / mm3 (poor response to prednisone).
Peripheral Blood Response to Multidrug Induction Therapy: Patients with the persistent
circulation of leukemic cells 7 to 10 days after mu ltidrug chemotherapy is started are at increased
risk of relapse compared to patients who discard peripheral blasts at one week. of started treatment.
The elimination rate of peripheral blasts has been determined to be of prognostic significance in
ALLs of both T and B lineage.
Minimal residual disease: Patients in clinical remission after induction therapy may have
minimal residual disease, e.g., leukemic cells that can only be detected by highly sensitive
techniques such as the polymerase reaction chain ( PCR) or specialized flow cytometry.
Risk-based treatment assignments are the main strategy
Therapeutic that is used in children with acute lymphoblastic leukaemia. This approach
allows children who have historically performed very well with modest therapy, thereby ridding
themselves of more intensive and toxic therapies, while allowing children who have historically
been less likely to survive long term., receiving more intensive therapies that can increase your
chances of healing.
As we saw in the Cell Cla ssification and Prognostic Variables section of this guide, several
clinical and laboratory qualities have been shown to have prognostic value. A subset of the known
prognostic factors e.g. age, white blood cell count at diagnosis, presence of specific cyt ogenetic

61 Keever MAV, Gómez JA, Núñez AE, Rojas JB. Metaanálisis sobre los factores pronóstico relacionados con la
mortalidad en niños con leucemia linfoblástica aguda. Bol Med Hosp Infant Mex. 2012;69(3):175 –89

abnormalities is used in the initial stratification of children with acute lymphoblastic leukaemia in
treatment groups who are at various degrees of risk of treatment failure (María Á, Gaviria, 2015)62.
Survival rates among children who are favoura bly at risk for age and GB exceed 80%,
while for children with "high risk" criteria, survival rates are approximately 70% or more. The
application of biological factors such as e.g., specific chromosomal shifts can identify patient
groups with an expected outcome survival rate that varies from less than 40% to more than 85%.
The treatment of children with acute lymphoblastic leukaemia is divided into stages:
induction to remission, post -remission or consolidation treatment, maintenance therapy or
continuati on. Given one of these stages of treatment, they are essential for a successful outcome.
In all patients, an intensification phase of therapy is carried out after induction of remission. The
intensity of both induction and post -induction therapy is determi ned by clinical and biological
prognostic factors that are used for risk -based treatment assignments.
The average duration of maintenance therapy in children with acute lymphoblastic
leukaemia varies from 2 to 3 years. Subgroups of patients with poor progn osis under current
standard therapy may require different treatment. For example, children with acute lymphoblastic
leukaemia represent a distinctive category of children whose risk of treatment failure is higher,
with those with MAL gene redeployment havi ng a poorer prognosis.
The three -drug induction regimen (vincristine, prednisone / dexamethasone, and
Asparaginase) in addition to intrathecal (IT) therapy, has resulted in complete remission rates of
over 95%. Dexamethasone is preferred over prednisone in younger patients with acute
lymphoblastic leukaemia, according to data obtained in a study by the Children's Cancer Group.
In general, patients will achieve a complete remission in the first 4 weeks to achieve
remission, they have a poor prognosis.
The ea rly institution of adequate CNS sanctuary therapy is critical to prevent CNS relapse.
The current goal of ALL therapy design is to achieve effective CNS sanctuary therapy by
minimizing neurotoxicity. All patients with ALL receive intrathecal chemotherapy w ith
methotrexate plus cytarabine and hydrocortisone.
Intrathecal therapy could also have a significant systemic effect that could result in a
decrease in the rate of medullary relapse. However, high -risk patients with a rapid early response
appear to have adequate CNS prophylaxis, only with intrathecal therapy. Children with acute
lymphoblastic leukaemia who have CNS disease at diagnosis (defined as greater than or equal to
5 white blood cells per mm3 in cerebrospinal fluid with lymphoblasts present) g enerally receive

62 María Á, Gaviria T. Quimiotera pia intensiva en niños con leucemia linfoblástica aguda. Análisis ínterin en un
centro de referencia en Colombia. 2015; available at
http://www.bdigital.unal.edu.co/50946/1/1037570604.2015.pdf

cranial radiation with or without concurrent spinal radiation, in addition to appropriate systemic
and intrathecal chemotherapy(Marwaha RK, Kulkarni KP, Bansal D, Trehan A., 2010: 249 –54)63.
The intensity of immediate post -induction chemot herapy varies considerably, but all
patients receive some form of "intensification" after remission is achieved and before continuing
maintenance therapy is started. Intensification could include the use of intermediate or high -dose
methotrexate, the use o f drugs similar to those used to achieve remission, the use of different
combinations of drugs of little -known resistance to the drug combination used in the therapy of
induction, the extended use of high doses of L -asparaginase, or combinations of the abo ve
mentioned (Catalina García B, López de Ayala López MC, García Jiménez A., 2014:462 –85)64.
In children with the average -risk disease, an attempt has been made to limit exposure to
drugs, such as anthracyclines and alkylating agents, which are linked to a n increased risk of
developing late toxic effects. For example, regimens with a limited number of courses of
intermediate or high -dose methotrexate have been used in children with standard acute
lymphoblastic leukaemia with good results. Another treatment approach to reduce the late effects
of therapy uses anthracyclines and alkylating agents but limits the cumulative dose to an amount
unrelated to substantial long -term toxicity. An example of this approach is the use of "late
enhancement," in which patient s receive an anthracycline -based reinduction regimen and a
cyclophosphamide -containing reconsolidation approximately 3 months after remission is achieved
(Ricardo Manuell -Lee G, Cortés -Gallo G, Medina Sansón A, Garduño Espinosa J, Enrique
Rendón -Macías M, Carolina Reyes -Zepeda N, 2012)65.
The backbone of maintenance therapy in most protocols includes oral daily mercaptopurine
and weekly oral methotrexate. If the patient has not had cranial irradiation, intrathecal
chemotherapy is generally administered for s anitary CNS therapy during Maintenance therapy.
It is important for treating physicians to recognize the fact that some patients may develop
severe hematopoietic toxicity when receiving conventional doses of mercaptopurine, due to an
inherited deficiency o f S-thiopurine methyltransferase, an enzyme that inactivates mercaptopurine.
These patients can only tolerate mercaptopurine if they are administered much lower doses than
conventionally administered. Maintenance chemotherapy generally continues until 2 or 3 years of
continuous complete remission. Extending the duration of maintenance therapy to 5 years does not

63 Marwaha RK, Kulkarni KP, Bansal D, Trehan A. Acute lymphobla stic leukaemia masquerading as juvenile
rheumatoid arthritis: Diagnostic pitfall and association with survival. Ann Hematol. 2010;89(3):249 –54
64 Catalina García B, López de Ayala López MC, García Jiménez A. Los riesgos de los adolescentes en Internet: Los
menores como actores y víctimas de los peligros de Internet. Rev Lat Comun Soc. 2014;69:462 –85.
65 Ricardo Manuell -Lee G, Cortés -Gallo G, Medina Sansón A, Garduño Espinosa J, Enrique Rendón -Macías M,
Carolina Reyes -Zepeda N, et al. Boletín Médico del [Inter net]. Vol. 69. 2012. available at
www.himfg.edu.mx%5Cnwww.nietoeditores.com.mx

improve results. The Role of Bone Marrow Transplantation for Chromosome Positive Acute
Lymphoblastic Leukaemia .
Philadelphia: Bone Marrow Transplan tation (BMT), in which a sibling with the same
histocompatibility antigen is used as a donor, appears to improve the odds of disease -free survival
in Philadelphia -positive acute lymphoblastic leukaemia.
The results of a bone marrow transplant using an unre lated and only partially matched
donor is inferior to chemotherapy. Treatment options under clinical evaluation one of the most
important therapeutic strategies, used in children with acute lymphoblastic leukaemia, is to assign
treatment, based on risk, an d protocols are designed for specific populations of patients with
different degrees of risk of treatment failure.
Children under two years of age with acute lymphoblastic leukaemia: These children, due
to their distinctive biological characteristics and their high risk of suffering from leukemic
relapses, are subjected to treatment under protocols strictly designed for this patient population
(Rafael J, Méndez L, Ceballos EC, Genaro O, Navarro L, Alfaro CC, et al.,2011:111 –5)66.
Childhood acute lymphoblas tic leukaemia – recurrent:
In patients with early bone marrow recurrence, allogeneic transplantation from a sibling
with identical HLA or a non -familial donor who has been properly paired performed during a
second remission has resulted in leukaemia -free s urvival, longer than a chemotherapeutic
approach. A retrospective case control study indicates that transplant conditioning regimens that
include total body irradiation (ICT) produce higher cure rates than preparative regimens for
chemotherapy alone (López -Hernández MA, Alvarado -Ibarra M, Jiménez -Alvarado RM, De
Diego -Flores JE, González -Avante CM. , 2008:485 –9)67.
Patients who go into remission continue to be examined regularly by the doctor. Once
remission has been induced and subsequent therapy has been c ompleted, it is necessary to continue
with a careful periodic evaluation of the patient's health, make blood cell counts and, if necessary,
marrow transplants. Over time, evaluations may become more spaced but should continue
indefinitely. While current th erapy for acute lymphocytic leukaemia can cure most children, the
therapy can have long -term consequences, including effects on growth, psychological
development, and others. Due to these possible side effects, it is important to continue the follow –
up for a long time and with long -term medical advice.

66 Rafael J, Méndez L, Ceballos EC, Genaro O, Navarro L, Alfaro CC, et al. Leucemia Linfoblástica Aguda.
Cancerología. 2011;111 –5.
67 López -Hernández MA, Alvarado -Ibarra M, Jiménez -Alvarado RM, De Diego -Flores JE, González -Avante CM.
Adolescentes con leucemia aguda linfoblástica de novo: Eficacia y seguridad de un protocolo pediátrico versus uno
de adultos. Gac Med Mex. 2008;144(6):485 –9.

1. The PED QL cancer module 3.0 instrument has not been previously applied in Honduras,
so there are no previous reference data to support us with the research line.
2. The study is limited in itself to an ag e range of 8 to 18, however, the data that should be
obtained in early anxieties from 0 to 8 are not valuable, since the information is only given by the
caregiver and is not You can make a comparison of the patient and the caregiver.
3. The investigation was carried out in a single period, without being able to determine new
events that could modify the quality of life of patients with ALL throughout their disease.