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in this lecture we will review leukemia
and children so leukemia is the
malignant transformation and
proliferation of Hamato poetic cells so
we have acute leukemia which is a clonal
expansion of immature precursors and we
have chronic leukemia which is mature
bone marrow components that are then
becoming clone so symptoms can occur
from a lack of normal bone marrow cell
production or from accumulation of
malignant cells in tissues that
otherwise shouldn't have them so let's
go through the epidemiology of leukemia
and children it is the most common
pediatric malignancy 30% of all newly
diagnosed children with cancer have
leukemia and Bowie is typically get it a
little bit more than girls so we break
down leukemia typically in kids into
four major types by far and away the
most common types are the first two
let's go through these first we have
acute lymphoblastic leukemia acute
lymphoblastic leukemia or al L is very
common in kids
it's a proliferation of B and T cell
lymphocyte precursors like you can see
here it typically happens in children
between the age of two and five and
again boys a little more commonly than
girls Caucasians are at greatest risk
for a ll comparing that to AML which is
acute myelogenous leukemia
AM L is a cloner clonal proliferation of
myeloid precursors so there are many
subtypes of AML based on the morphology
of the cells that are growing and the
saito genic translocations that have
occurred which caused these cells to
become clonal in nature there's a
generally bimodal incidence in terms of
when children get this disease there's
one peak in little tiny kids under 2
years of age and then
again in adolescence this for AML unlike
a ll the rate in boys and girls is about
the same and this is associated with
some toxic exposures also some genetic
predispositions for example children
with Down syndrome have a 50 fold
increase in their risk for AML remember
that Down syndrome and AML strong
association now we would switch gears to
chronic disease and this is chronic
myelogenous leukemia which is less
common in kids this is an uncontrolled
growth of myeloid cells and the
incidence increases through childhood
and adolescence often these patients
have a fusion protein the BCR Abel gene
this constituents tyrosine kinase the
mutation in this translocation between
chromosome 9 and chromosome 22 causes a
continuously on activation of tyrosine
kinase and lastly we'll talk very
briefly about the very mild form of
leukemia which is juvenile Milo
monocytic leukemia or JMML JMML is very
rare it's usually diagnosed before the
age of three and the etiology is
basically unknown it is associated
however with a few genetic conditions
like Down syndrome neurofibromatosis
li-fraumeni syndrome and Fanconi anemia
so let's back off now and talk about
what are the general symptoms of
leukemia if a child it has leukemia what
do they look like well first of all
they're often lethargic they have less
energy to get through their day
sometimes they have respiratory distress
if there's a mediastinal mass that might
be pressing on the trachea or something
but usually it's a nonspecific kind of
lethargy some fatigue they may have
increased bleeding if their platelet
counts are down and they may have
increased rates of infections children
may present with bone pain as their
chief complaint when they have leukemia
also you may find on exam that they have
fever power from an anemia tachycardia
from an anemia and bruising in petechiae
from low platelet counts they may have
lymph adenopathy hepatosplenomegaly or
in boys testicular enlargement from some
tissues growing with cancer cells in
them specifically the lymph and the
splenic system they may have facial
swelling and wheezing and tachypnea if
they happen to have a mediastinal mass
and they may have CNS involvement which
actually is not uncommon in áall so how
do we diagnose this problem well the
first mainstay of picking up anemia is
the CBC and frequently we will find
signs on the CBC that something isn't
right we usually will see what we say is
two cell lines down sometimes one cell
line down but often that could be
something else for example if a patient
has thrombocytopenia only this could be
immune thrombocytopenic purpura not
cancer we would treat that very
differently but typically they'll have
more than one cell line down which means
they may have some anemia some
thrombocytopenia some leukopenia some
leukocytosis at times with a very high
white count or neutropenia you also may
see a particular type of cell called a
blast when you say a blast on a CBC
differential you are should be highly
concerned that that patient might have
cancer and you should probably refer
that patient to a hematology oncologist
in CML we sometimes see very marked
hyper leukocytosis with white counts in
the fifty to a hundred range and we
often see normal my load precursors on
those CBC's also in patients where we
suspect they might have leukemia we
often will check a chemistry panel to
look for signs of tumor lysis syndromes
such as a high potassium or high
phosphate so we
we'll check that but that's not a great
diagnosis mechanism though rarely you
may see it also we could do if the
patient specifically had CML we could
look for the bcr-abl gene that's usually
a little bit later on
what radiology do we get we usually get
a chest x-ray and a chest x-ray can
often show a large mediastinal mass like
you can see in this patient with a
widened mediastinum to confirm the
diagnosis we will do a bone marrow
aspiration and a biopsy to try and get
some of that bone marrow tissue that is
then sent for cytology and you can
actually identify the type of cancer off
of cytology additionally we will often
do a lumbar puncture to inspect for CNS
involvement especially in a ll so who is
it highest risk when they have leukemia
who are the high risk patients well
children more than ten years and less
than one year are at higher risk the
children between one and ten are at
lower risk if their white count is very
very high they're at higher risk if they
have a T cell phenotype they're at
higher risk and if they have cytogenetic
changes in their leukemia cells they're
at higher risk and lastly make sense if
they're not responding well to therapy
they're at higher risk so what is the
therapy we're giving well it depends on
the type of cancer obviously in fact
there are complicated pathways and
roadmaps that are established by multi
Center groups that are how we treat
these children in a very standardized
way so what you'll see is if you're
taking care one of these patients
they'll have a road map that'll say
things like for example on day seven
they have to get intrathecal
methotrexate on day 14 they'll get
something else it's a very prescribed
pathway we try very hard to follow the
road map because it's been shown to have
improved outcomes so what is that road
map involve well an al L this is going
to be a multi agent chemotherapy with
multiple agents generally for two to
three and a half years and also they
will get some prophylactic intrathecal
chemotherapy and/or radiation
to sanctuary sites for AML we will do
multi agent intensive chemotherapy for
six to nine months but some of these
patients will weren't getting a Hamada
poetic stem cell transplant for CML
we're going to give single agent therapy
with tyrosine kinase inhibitors for the
BCR Abel gene and a hematopoietic stem
cell transplant for a poor response and
for JMML these patients awfully require
a bone-marrow transplant so what's the
prognosis for these patients
surprisingly good for al more than
eighty percent and even as high as
ninety five percent of patients and
low-risk groups are going to survive
they're al l this is a great
accomplishment we have in pediatrics for
AML it really depends on the subtype of
animal but it's probably around fifty
percent survival rate for CML this is a
lifelong disorder with tyrosine kinase
inhibitor therapy and for JMML about
survival of about forty percent
unfortunately with a bone marrow
transplant which requires all the
complications of bone marrow transplants
but in general most children have al and
most children have a pretty good
prognosis it being cancer so that's my
review of leukemia in children thanks
for your time
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