Pediatric Board Review Course
Pediatric Hematology/Oncology
Kusum Viswanathan, MD
Vice Chair, Dept of Pediatrics
Brookdale Univ Hospital and Medical Center
Case 1
6 week old term infant
refd for anemia. Hb 7.5,
Retic 2 %. Mother O+,
Baby A -, Direct
Coombs +, Cord blood
Hb 14.2 g/dL. Jaundice
of 15mg/dL at 48 hours
of life, recd photo Rx
and discharged at 5
days. No complaints,
pale, Bili 3.5, Direct 0.5.
Blood smear shows
spherocytes
1.
2.
3.
4.
5.
Most likely
explanantion:
Rh hemolytic
disease
G 6 PD deficiency
Hereditary
spherocytosis
Physiologic anemia
ABO incompatibilty
Newborn -anemia
Hemoglobin at birth is 17 g/dl, MCV over 100.
Falls to 11-12 by 6 weeks of age- nadir.
Erythropoietin production shifts from liver to kidneys and
reduces because of increase in PaO2.
Anemia at birth could be :
–
–
–
–
May not have equilibrated- repeat
Hemorrhage, may not have had time to mount a retic response
Acute hemorrhage- pallor and tachypnea
Look at MCV- low MCV-suggestive of
chronic feto-maternal hemorrhage
Alpha Thalassemia trait.
– Kleihauer-Betke- Hb F resistance to acid elution
Newborn-Thrombocytopenia
A newborn has a completely normal physical exam
except for a few petechiae. Platelet 50,000.
Differential diagnosis:
– Production defects:
TAR, Magakaryocytic hypoplasia, Trisomy 13, 18.
Wiskott-Aldrich(small plt, X-linked, Ezcema , SCT cure)
Infections- viral, bacterial, Infiltration (Gauchers, Niemann
Paick, Leukemia)
– Destruction:
Allo-immune- Platelet group incompatibilty
Auto-immune: Mat ITP, Drugs (thiazide, tolbutamide), SLE
Infections: CMV, Rubella, herpes, DIC
Loss: Kasabach- Merritt syndrome (hemangiomas, DIC- Rx
DIC and hemangioma with Steroids, interferon, VCR)
Immune thrombocytopenia
Auto-immune: Pregnant women with ITP/Hx of ITP
–
–
–
–
Passive transfer of antibodies (IgG) from mother.
Even when mother has a normal platelet count (Splenectomy)
Nadir-few days; Platelets < 50,00 have 1% risk of ICH.
IVIG to mother, Fetal platelet counts, C sec, US, IVGG to baby
Iso-Immune: Normal platelet count in mother
–
–
–
–
–
–
–
Similar to Rh disease; PL A1 antigen/ Zw a negative mother.
97% of population is PL A 1 positive
Sensitization early in pregnancy
Plt function defect because Anti-PL A1 interferes w/aggregation.
Severe bleeding more likely; first born affected;
Recovery in 2-3 weeks
Mother’s washed (PLA1 neg) platelets; IVIG; Ultrasound;
Steroids
Kasabach- Merritt, TAR
Older child-Thrombocytopenia
10 year old male treated with Valproic acid for seizures
presents with fever. He appears Ok with no skin lesions,
lymphadenopathy or hepatosplenomegaly.
CBC WBC 5, Hb 12, Platelet 65,000. BUN 12,
Creatinine 0.6 md/dl.
What is the Most likely cause:
–
–
–
–
–
ITP (Immune thrombocytopenic purpura)
HUS (Hemolytic Uremic Syndrome)
HS Purpura (Henoch- Schonlein Purpura)
ALL (Acute lymphoblastic leukemia)
Drug induced purpura
Other causes
Hemolytic Uremic Syndrome
– Hemolysis, sick patient, Uremia, microangiopathic
Henoch-Schonlein Purpura
– Purpuric lesions on lower extremities and buttocks
– Abd pain, arthritis. IgA deposition
ALL
– lymphadenopathy (LN), hepatosplenomegaly,other
cell lines affected
Drug induced– Likely
– By reducing production or increasing destruction
Petechiae, HSP
ITP
Usually acute onset; immune mediated; post viral
Peak 2-5 years of age, males=females
Spontaneous bruises, petechiae
PE –no lymphadenopathy (LN), hepatosplenomegaly.
CBC- other cell lines normal, large plts on smear
Treat if plt< 10,000 or wet ITP, avoid NSAIDS, Aspirin
Treat- IVIG best response, 48-72 hours; Side effects.
– Anti-D (WInRho) Rh+ ,hemolysis, quick response
– Steroids good response, SE, inexpensive, need BM
BM- Increased megakaryocytes, otherwise normal
Large platelets
Normal platelet 7-10 days
Large platelets:
– ITP
– May Hegglin (Dohle
bodies in neutrophils, Plt
function normal).
– Bernard Soulier
syndrome (AR, Plat
function disorder).
Small platelets: Wiskott
Aldrich syndrome ( X-linked,
recurrent infections,eczematoid
rash, plt dysfunction)
A 2 year old boy presents for evaluation of a chronic
pruritic eruption. His medical history is remarkable for
recurrent epistaxis, otitis media, and pneumonia.
Physical examination reveals erythematous, slightly
scaling patches on the trunk and in the antecubital and
popliteal fossae. Petechiae are present profusely. Of
the following, these findings are MOST suggestive of
1.
2.
3.
4.
5.
Acrodermatitis enteropathica
Ataxia telangiectasia
Atopic dermatitis
Langerhans cell histiocytosis
Wiskott-Aldrich syndrome
Platelet function defects
Normal platelet number
Glanzmann thrombasthenia
– AR, Abnormal aggregation
– Bleeding disorder, check h/o consanguinity
Hermansky Pudlak Syndrome:
– AR, Decreased dense granules, In Puerto
Ricans, Oculocutaneous albinism
Thrombocytosis
H- Hemorrhage, Hereditary Asplenia, Down myeloprol.
IPLATELES-
Infections, Kawasaki, Immune:GVH, Nephrotic syndrome
Polycythemia vera, Myeloproliferative, Essential
Leukemia (CML)
Anemia,- Iron, Vit E, Sideroblastic
Tumors
Epinephrine, Steroids
Lymphoma, Hodgkins
Exercise, T- Trauma, Fractures
Splenectomy
Anemia
An 18 month old girl brought in for pallor. Normal diet
and PMH. She is alert, interactive, only pallor, normal
vital signs, No hepatosplenomegaly, lymph nodes or
bruises.
CBC- Normal WBC, Plt, Hb 4.5g/dl, MCV 74,
Anemia
– Reduced production
– Increased destruction
– Loss
What else do you want??
Reticulocyte count
Normal/Low- reduced production
– Iron deficiency anemia- MCV will be low
– ALL (leukemia)- other findings, LN, HSM
– Diamond Blackfan anemia- Us < 1 year of age;
facial/thumb abn, Cong heart dis, MCV Incr, rbc ADA
increased, responds to steroids, BMT curative.
– TEC: Over 1 year of age, Pallor, transient rbc
production failure, improves, MCV and Hb F high
during recovery, rbc transfusion, rbc ADA normal .
Normal smear
Microcytic Anemia
The diet of an 18-month-old child consists only of milk. She
consumes 60 oz/day. Findings include: Comfortable, pallor,
resting heart rate 85 beats/min, hemoglobin concentration 6.5
g/dL; mean corpuscular volume 57 fL; reticulocyte count 1.2%;
and guaiac-negative stool. Peripheral smear reveals marked
hypochromia and microcytosis.
Of the following, the most appropriate INITIAL step in the
management of this patient is to
A.
B.
C.
D.
E.
administer intramuscular iron
begin oral ferrous sulfate
obtain serum iron levels
refer for bone marrow evaluation
transfuse with packed red blood cells
Microcytic anemia
Iron deficiency
Low MCV, low MCHC, low retic, RDW will be normal
initially, will increase after treatment, Low Iron, Incr TIBC,
Transferrin low, Ferritin low
Causes: Inadequate dietary intake
– Toddlers, too much milk, less solids, Breast fed need
iron supplements
– poor absorption
– Blood loss: Menstrual, GI tract, Meckels, Epistaxis
D/D:
Thalassemia trait- MCV much lower in prop to anemia,
Anemia of chronic disease- low Fe, low TIBC,
normal/high Ferritin.
Thalassemia Minor
Quantitative defect in
globin chains
– Reduced production of
Beta chains
Hb electrophoresis
– Hb A- 2 Alpha, 2 Beta
– Hb F- 2 Alpha, 2 Gamma
– Hb A2- 2 Alpha, 2 Delta
Excess Alpha combines
with Gamma, DeltaIncreased Hb F and A 2.
Smear abnormalities
significant even with
MILD anemia.
Anemia
Low MCV, normal RDW,
normal retic
Smear shows
anisopoikulocytosis,
target cells, microcytes,
misshapen cells,
basophilic stippling
Hb Electrophoresis:
Increased Hb A2 and/or
F.
Normal iron studies, no
response to iron
Thalassemia Major
No production of Beta chains
Autosomal recessive
25 % chance with each pregnancy
Pre natal testing for carriers
Chorionic villous sampling for diagnosis
Transfusion dependent-allows for normal development
Pen Prophylaxis, Anti oxidants
Splenectomy after age 5
Iron overload- inherent and transfusion
Need chelators
Thalassemia- Alpha
Reduced Alpha chains
4 types- carried on 4 allelles. (x x/x x)
One absent- Silent carrier (x-/x x)
2 absent- Alpha Thal trait (xx/- - or x -/x -)
3 absent- Hb H disease (x -/- - ) Has 4 excess
Beta chains)
4 absent- Hydrops fetalis (- -/- -)
NB period: Excess Gamma forms Hb BartsFAST moving Hb on Newborn screening
Case
3 year old patient is brought to the ER with
complaints of feeling very tired over the
past 3 days.
Patient is pale, jaundiced with the spleen
tip palpable.
CBC Hb 5, Retic 5 %, LDH Increased,
What does this sound like??
Reticulocyte count- Increased
Hemolysis
– IntrinsicMembrane defects-Hereditary spherocytosis (HS)
Enzyme-G 6 PD deficiency
Hemoglobinopathies
– Extrinsic- AIHA (Auto-immune hemolytic anemia),
DIC, IV hemolysis
Loss
– Blood loss
Hemolytic anemia
History; Recent infection, drug exposure,
illness, dark urine, anorexia, fatigue, pallor
Family h/o gallstones, splenectomy
Physical Examination: Pallor, Tachycardia,
Tachypnea, Splenomegaly.
Peripheral smear: Blisters, spherocytes
G-6PD deficiency
A previously normal AfricanAmerican child visited Africa
and was given malarial
prophylaxis. He experienced
pallor, fatigue, and dark urine.
His hemoglobin level decreased
from 14.8 to 9 g/dL. The most
likely diagnosis is
–
–
–
–
Blister cells
Bite cells
Hereditary spherocytosis
Sickle cell disease
Hepatitis
G6PD deficiency
Avoid certain medications
(Sulfas), Fava beans in
Mediterranean.
Seen in African American- avoid
moth balls.
Blister cells
Bite cells
Spherocytes
Spherocytes
Nucleated rbc
Coombs-AIHA
Osmotic fragility-HS
HS- with severe anemia
All patients with hemolytic anemia are susceptible
A 6 year old girl who has hereditary spherocytosis
presents with a 1 week history of fever. Physical
examination and history reveal abdominal pain,
vomiting, fatigue and pallor. Her hemoglobin is
typically about 10 g/dL with a reticulocyte count of 9%,
but now, her hemoglobin is 4 g/dL and the reticulocyte
count is 1%. Her bilirubin is 1 mg/dL. Of the following,
the MOST likely cause for this girl’s present illness is
infection with
–
–
–
–
–
Coxsackie virus
Epstein-Barr virus
Hepatitis A virus
Influenza A virus
Parvovirus B19
Newborn Screening
You get a call from a frantic parent because she
received a letter from the State regarding her
baby’s test results on NBS.
FS- SS disease, S-B0 Thal, Sickle cell w/ HPFH.
FSA- Sickle B+ thal, Sickle cell trait
FSC- SC disease
FAS- Sickle cell trait
FAC- Hb C trait
FAE- Hb E trait
FE - Hb EE disease, E-Thal
Sickle cell
Hemolysis- life span 20-50
days. Abnormal cell shape,
abnormal adherence to
endothelium, decreased
oxygenation, Increased
polymerization.
Symptoms start by 2-4 months
of age.
Hb electrophoresis, S >75 %.
Start Penicillin daily and give
until age 5. Prevention of
pneumococcal infections.
PPV (Pnu-23) age 2, 5
Folic acid daily
Sickle cell- Higher risk
High WBC
Low Hemoglobin
Multiple episodes of dactylitis
Low Hb F
Associated Alpha thal trait- better clinical
course
Sickle cell crises
Vaso-occlusive crisisdactylitis, long bones,
back, chest. Trt. Pain
meds, hydration.
Aplastic crisis: low Hb,
low retic, Sec to
Parvovirus infection.
Splenic sequestration
crisis: spleen palpation
Hyperhemolytic crisis
Case
12 year old female with SS disease
complains of right sided chest pain and
upper back pain for one day.
P/E reveals slightly reduced breath
sounds and a Pulse OX of 86 %. CXR
shows an infiltrate on the right lower lobe.
What is your diagnosis?
What will you do next?
Sickle cell
Acute Chest Syndrome
New infiltrate on X-ray, fever, chest pain,
back pain, hypoxia.
Due to infarction, infection, BM fat
embolism
Treat: Antibiotics to cover pneumococcus,
Mycoplasma, Chlamydia, Bronchodilator,
Oxygen, Incentive spirometry, transfusion,
Steroids (controversial).
Avoid overhydration
Pulmonary Hypertension
Prevalence of pulmonary HT in SCD from
20-40 %.
The presence of hemolysis, chronic
anemia, and the need for frequent
transfusions were directly associated
with development of PHT.
On follow-up, PHT was significantly
associated with an increased risk of death.
-Am J Hematol July 2004
-N Engl J Med Feb 2004.
TCD- Transcranial Doppler
A routine TCD on a 4
year old patient with
SS disease shows a
Cerebral blood flow
(CBF) of 210
cm/second.
What is the next
step?
STOP studies- STOP
I and II
Sickle cell and Stroke
Affects 10 % of patients
Infarctive stroke (younger patients) and
Hemorrhagic stroke (older)
STOP I study established the role of yearly TCD
(transcranial doppler) to measure cerebral blood
flow velocity as a tool for determining stroke risk.
Transfusion therapy as current therapy for
high risk patients (CBF> 200cm/sec)
Reversal of CBF velocity is not sufficient to stop
transfusion therapy. (STOP II)
Sickle cell and Transfusions
Transfusion indications:
–
–
–
–
Acute anemia (Aplastic, Hyperhemolytic, Sequestration)
Hypoxia (ACS, chronic lung disease, Pulmonary hypertension)
Stroke and stroke prevention
Intractable pain, pre-operative
Types of transfusions
–
–
–
–
Intermittent
Chronic simple
Exchange (Partial, Total, Erythrocytapheresis)
Hypertransfusion (transfusions in an effort to prevent patient
from producing their own red cells)
Iron overload
One unit -200mg Iron
No physiologic way of
removal
10-20 transfusions
Desferioxamine available.
Can be given IV or subq
infusion or subq shots.
Compliance an issue.
December 2005- Oral
chelator available
(Deferasirox)- FDA
approved.
Sickle cell and Hydoxyurea
FDA approved for adults
Studies in children demonstrated efficacy
and safety.
Increases hemoglobin F level
Increases hemoglobin
Decreases WBC – ancillary effect
Hydroxyurea is recommended by the
hematologist for patients who have recurrent
vaso-occlusive crises, Acute chest syndrome.
Other important points
Median life expectancy:
– Males 42 years, females 48 years
Improvement related to Penicillin,
immunizations, education.
Bone marrow transplant (BMT) is a cure
Cord blood storage
Case
A healthy 5 year old boy has a 2 day hx of
fever, P/E normal, No hepatosplenomegaly,
LN, no focus of infection. CBC WBC 3,
Neutrophils 25 %, Hb 12, Platelet 200X109/L,
ANC 750.
The most appropriate management would be:
1. Amoxicillin for 10 days
2. G- CSF for 10 days.
3. BM aspirate
4. Refer to a hematologist
5. Repeat CBC in 1-2 weeks
Neutropenia
Severe neutropenia ANC < 500/mm3
Viral infection(hepatitis, Influenza, Measles,
Rubella, RSV, EBV)- No Rx.
Cyclic neutropenia
– Sporadic Autosomal dominant disorder
– 21 day intervals, nadir < 200/uL
– G CSF treatment
Severe Congenital Neutropenia (Kostmann)
– AR, ANC< 200, BM arrest, high dose G CSF, risk of
malignancy (MDS/AML) and sepsis. BMT cure.
Neutropenia
AutoImmune neutropenia
– Self limited, G CSF only if necessary
– Mild infections
Schwachman-Diamond Syndrome
– AR, Exocrine pancreatic failure, short stature,
recurrent infections, mataphyseal dysostoses.
– G-CSF, Risk of myelodysplasia and AML, BMT
curative
Chronic benign Neutropenia
– ??AI, < 3 years of age, skin and mucous membrane
infections, Antibodies
Case
A 2-year-old boy has had several 10-day-long episodes of fever,
mouth ulcerations, stomatitis, and pharyngitis. These episodes have
occurred at about monthly intervals. Absolute neutrophil counts have
been 50/mm³on day 1 of each illness, 500/mm³ on day 10, and
1,500/mm³ on day 14.
Among the following, the MOST likely cause for the findings in this
patient is
A. chronic benign neutropenia
B. cyclic neutropenia
C. Schwachman-Diamond syndrome
D. severe congenital neutropenia
E.. transient viral bone marrow suppression
Approach to a bleeding patient
History:
– h/o trauma, H/o similar episodes
– h/o bruising, h/o surgery in the past
– h/o circumcision, bleeding from the umbilical
stump ,delayed wound healing
– Time of onset (Acute/chronic), any challenges
eg. trauma, surgery or menstruation
– Overall health ( well/sick); Evidence of shock.
– bleeding disorders in the family (maternal
uncles and aunts, grandparents)
Abnormal Bleeding
Epistaxis unrelieved by 15 minutes of
pressure, both nostrils, requiring an ER
visit, documented drop of Hb.
Menstrual periods( amount, pads,
duration)
Bleeding after procedures (circumcision,
dental extractions, T and A-delayed bleed)
Ecchymoses/bruising inconsistent with
the degree of trauma
Case
13 year old girl just started her periods and
has been bleeding for the past 16 days.
She has used 14 pads a day and is tired.
Her vital signs were stable, Hb was 9.5,
PT, PTT were normal. The mother had
heavy periods and her 6 year old brother
has nose bleeds for the past 2 years.
Bleeding patient
Physical Examination:
Type of bleeding: Superficial or deep
– Bruises, Petechiae
– Epistaxis, Gum bleeding, Excessive menstrual
bleeding
– Site of bleeding
– Bleeding into the joints and soft tissues
– Look for evidence of shock
– Medication history (Aspirin, NSAIDS)
Coagulation cascade
Lab studies
(What do they measure?)
CBC and Peripheral smear
PT, INR and PTT
– PT - Factor VII, common pathway
– PTT- Factor VIII, IX, XI, common pathway
Mixing studies (Inhibitors and deficiency)
Specific coagulation factor assays
Fibrinogen
Circulating anticoagulant
Mixing study
If PT or PTT is prolonged, ask for a mixing
study.
Mix patient plasma with equal amount of normal
plasma, the test will normalize if the abnormal
result is because of a deficiency in factor.
If there is an anticoagulant, it will not normalize
or even if it does, it will become abnormal again
after incubation.
Factor XIII and VII deficiency
Factor XIII
Rare Autosomal
Recessive
If all tests are normal:
– PT, PTT, Platelet count
and function, VW tests all
normal.
– Think of doing Factor XIII
assay for deficiency
Bleeding after umbilical
stump separation
Abnormal clot solubility in
5M Urea
Factor VII
Intracranial hemorrhage
Rare, homozygous state
Prolonged PT, n PTT
Treatment with
Recombinant F VII
Case
A healthy 2-day-old boy born at term undergoes circumcision
prior to discharge from the hospital. Bleeding was noted at the
site of circumcision 10 hours after the procedure and has
increased steadily over the past 4 hours. Findings on physical
examination are unremarkable except for bleeding along 2 to 3
mm of the surgical site; there are no petechiae or purpura.
Of the following, the MOST likely cause of the bleeding is
A.
B.
C.
D.
E.
disseminated intravascular coagulation
factor VIII deficiency hemophilia
immune thrombocytopenic purpura
neonatal alloimmune thrombocytopenia
von Willebrand disease
Bleeding disorders
Tests for bleeding
Hemophilia A
Hemophilia B
Hemophilia C
VW Disease
Hemophilia
Factor VIII deficiency (Hemophilia A)-85%
– X-linked recessive, Carriers asymptomatic
– Severe<1%, Moderate 1-5, Mild 6-30 %
– Treat Recombinant Factor VIII1 unit/kg raises factor
level by 2 %. Half life 12 hrs. DDAVP for mild cases.
– Joint bleeds need100%, muscle bleeds 50 %.
– 30 % develop inhibitors after infusions with
concentrate (Approx 50 infusions)
Factor IX deficiency (Hemophilia B)
– X-linked recessive, less common
Hemophilia
A patient with Hemophilia A has asked you
about the possibility of his children being
affected by the disease. The partner is normal.
a. There is a 50 % chance that his sons
will have the disease.
b. There is a 50 % chance that his
daughters will be carriers
c. There is a 100 % chance that his sons
will have the disease
d. There is a 100 % chance that his
daughters will be carriers
Answer was d
Case
13 year old girl just started her periods and
has been bleeding for the past 16 days.
She has used 14 pads a day and is tired.
Her vital signs are stable,
Hb 9.5, PT, PTT normal.
The mother had heavy periods and her 6
year old brother has nose bleeds for the
past 2 years.
Likely to have:
Von Willebrand’s Disease
1-2 % of population
Type I - 80 % of cases; Quantitative defect, Autosomal
dominant (AD)
Type 2 - 15-20 %, Qualitative defect
– 2A, 2b (thrombocytopenia), 2M,
– 2N (AR)
Type 3 - Severe (similar to hemophilia A)
Autosomal recessive (AR)
DDAVP- Releases VWF from endothelial cells and stabilizes
Factor VIII
– SE: Water retention, Tachyphylaxis, hyponatremia.
– For mild Hemophilia, Type I VWD, 2
– Contra-indicated in Type 2B
Plasma derived VWF containing concentrates
Thrombophilia- Case
A 14 year old male presents with chest pain and difficulty
breathing. He notes that his right calf has been swollen
for the last 3 days and he has difficulty placing his foot
on the ground. P/E Pain on dorsiflexion, Air entry
reduced. CXR and EKG are normal. VQ scan shows a
filling defect and a diagnosis of DVT and pulmonary
embolism is made.
What are the important questions on history?
– History of DVT in family members
– H/o recurrent late miscarriages in mother and her sisters.
– H/o trauma and precipitating factors
Causes
Factor V Leiden (Activated Protein C resistance)
Prothrombin G 20210A gene mutation
Protein C deficiency and activity
Protein S deficiency and activity.
Anti thrombin III deficiency and activity.
Hyperhomocystenemia
Antiphospholipid syndrome
Rare disorders-Dysfibrinogenemia
Hypercoagulable states
Factor V Leiden- 40-50 % cases
– Abnormal factor V cannot be cleaved and inactivated
by Protein C & there is thrombosis.
– Common in Caucasians (5.3 %)
– Non-O blood group more prone to thrombosis
– Homozygotes 1%
Protein C- Vit K dependent, produced in liver
– Activated PC inactivates coagulation factors Va and
VIIIa, The inhibitory effect is enhanced by Protein S.
– Venous thromboembolism, Neonatal purpura
fulminans, Warfarin-induced skin necrosis.
Hypercoagulable states
G20210A Prothrombin mutation
– Increase in the prothrombin, a precursor of thrombin
– Vitamin K-dependent protein which is synthesized in
the liver
– Heterozygous carriers have an increased risk of deep
vein and cerebral vein thrombosis.
Antithrombin (AT, formerly called AT III)
– vitamin K-independent glycoprotein that is a major
inhibitor of thrombin and factors Xa and IXa.
– In the presence of heparin, thrombin or factor Xa is
rapidly inactivated by AT; this is referred to as the
heparin cofactor activity of AT.
Transfusion
A 4-year-old boy develops massive bleeding following a
tonsillectomy. A transfusion is indicated, but his parents are
extremely concerned about the risk of a transfusion-mediated
infection. They want to know what tests are performed on donated
units of blood before they consent to the procedure.
Of the following, your discussion is MOST likely to include the
statement that
A. all units are tested only for hepatitis B and C
B. all units are tested only for human immuno-deficiency virus (HIV)
C. all units are tested for HIV, hepatitis B, and hepatitis C
D. all units are tested for HIV, hepatitis B, hepatitis C, sickle cell trait,
cytomegalovirus, and Epstein-Barr virus
E. only units obtained from donors who have one or more risk factors
are screened for HIV
Transfusion- Notes
CMV negative- give leukocyte reduced.
Irradiated products- To prevent GVHD
Washed cells
Phenotype matched
– To prevent allo-immunization
Sickle negative
CANCER IN CHILDREN
Childhood Cancer Distribution
Distribution-All ages
Leukemia
Lymphoma
Brain Tumor
Soft tissue sarcoma
Germ call
Bone
Neuroblastoma
Renal
Retino
Hepato
Carcinoma
Other
Cancer in Children
Leukemias, Brain
tumors, Lymphomas
2nd leading cause of
death 1-14yrs
12,400 cases per
year
Proto-Oncogenes imp
for function-Activated
-Amplification --n-myc
-Point mutation-NRA’s
-Translocation- Ph
chromosome t (9:22);
BCR-ABL
Case
18 month old comes to the clinic with
complaints of pallor. No fever, appetite
change, wt loss. P/E Pale, HR 110/min, No
HSM, bruise left buttock, arms and abdomen.
MOST likely diagnosis
1. ALL
2. Child abuse
3. ITP
4. Iron deficiency anemia
5. TEC (Transient erythroblastopenia of
childhood)
ALL
(Acute Lymphoblastic leukemia)
This suggests 2 cell lines are affected.
Consider ALL, viral infections, aplastic
anemia, myelofibrosis, neuroblastoma.
Child abuse: unlikely to have pallor unless
massive trauma
ITP: can have mild anemia, but here, the
HR suggests significant anemia
Iron def and TEC: No bruising
A 6-year-old girl has had diffuse aching in her arms, legs, and back
for more than 2 weeks. Results of laboratory tests include
hemoglobin, 9.4 g/dL; white blood cell count, 5,600/mm³ with no
abnormal cells noted on smear; and platelet count, 106,000/mm³.
Radiographs of long bones reveal osteolytic lesions and radiolucent
metaphyseal growth arrest lines.
Of the following, the MOST likely cause of these findings is
A.
B.
C.
D.
E.
acute lymphoblastic leukemia
aplastic anemia
Gaucher disease
lead poisoning
multifocal osteomyelitis
ALL
(Acute Lymphoblastic leukemia)
Can present with
generalized bone pain
Bruising, nose bleeds
Unusual fevers,
infection
Lymphadenopathy,
hepatosplenomegaly
ALL
(Acute Lymphoblastic leukemia)
Abnormal to see blasts in the peripheral smear
Diagnosis: >25 % blasts in the BM.
Normal marrow has 5 % blasts
Single most common childhood cancer (29% of
all childhood cancers); 2500-3500 cases per
year
Peak age 2-5 years
More likely in Trisomy 21, Ataxia-Telangiectasia,
Bloom syndrome, Fanconi anemia.
ALL Treatment
Induction: 4-6 weeks, 95 % remission;
Vincristine, Corticosteroids, L-Asparaginase and
Anthracycline
Consolidation /delayed Intensification:
6-12 months; rotating drugs.
Maintenance : Daily oral 6-MP, weekly MTX,
Monthly pulses of Vincristine and Steroid.
CNS prophylaxis: Intrathecal chemo
CNS Therapy: RT + Int Systemic chemo
Testicular disease: RT
ALL- Prognosis
Prognosis: WBC, Age, Cytogenetics
– good if hyperdiploidy, trisomy 4,10,t (12,21)
– Bad if Philadelphia chr t (9,22),t(4,11), t(8,14)
Immunophenotype: Pre-B, B, T
Early response, Minimal residual disease (MRD)
Standard risk: 85 % survival
High risk: 65 % survival
Very low risk: 90% survival
Infants: 50 % survival
Early relapse is a poor sign
Down Syndrome and Leukemia
10-20 fold increase
ALL:AML 4:1
< 2 years: M7 AML
DS: 400 fold Increase in M7 AML
Superior response to Rx of AML
Transient Myeloproliferative disorder in NB
which resolves within 3 months.
– No clonal cytogenetic abnormality.
Rx : Exchange or low dose cytoreduction.
Higher chance of M 7 AML. (30% in some reports)
Acute Myeloid Leukemia (AML)
20 % of all leukemias
Increased incidence in < 1 year of age
Higher incidence:
– Downs, Fanconi, Bloom, DBA, Kostmann,
Neurofibromatosis I, Schwachman-Diamond
Sx: Fever, bleeding, pallor, anorexia, fatigue,
Bone/Jt pain, LN, GI Sx.
Chloromas (green) – solid collection in bone/soft
tissues
Types: M0-M7, commonest M2
M7- Downs syndrome
Acute Myeloid Leukemia (AML)
Treatment:
– Remission Induction, Consolidation, Maint
– BMT (matched sib donor) after remission.
– ATRA (form of Vit A-transretinoic acid) in APML
Results:
– HLA matched donor: 65 % EFS
– No donor 40-50 %
Prognostic features:
– Favorable: t(8,21), inv(16); Early remission;
FAB M4 with eosinophilia
– Unfavorable: Monosomy 7; WBC> 100,000;
Secondary AML; Myelodysplasia with AML
Hodgkin’s Lymphoma
Bimodal age distribution: first peak 20-30, again after
age 50. Rare < 5 years.
5 % of all malignancies; 40 % of lymphomas,
Sx: Painless adenopathy, 1/3 have “B” symptoms( fever,
night sweats, wt loss)
Pathology: Reed-Sternberg cell (large cell with
multilobed nuclei); B-cell, 4 subtypes.
Rx: based on stage; Staging depends upon one side or
both sides of the diaphragm. Stage !-2, EFS 85-90 %,
Stage 3-4; 75 % EFS.
Second malignancy in patients who have recd
combination chemo and RT-- Leukemia, NHL, Breast
cancer.
Non Hodgkins Lymphoma
Most common lymphoma in childhood
10-15 % of all cancers (after leukemia, Brain tumor)
50 % of all cancers in Africa (Burkitt’s)
More in males, Caucasians
Common in immunodeficiencies (SCID, Wiskott-Aldrich syndrome,
HIV, following stem cell transplant.
Types:
– small, non-cleaved 40 % (B cell)
– Lymphoblastic lymphoma 30 % (T cells)
– Large cell 20 % (B, T, indeterminate)
Sites: Abdomen, mediastinum, head and neck
Majority are high grade
Chromosomal translocations involve c-myc oncogene (chr 8)
Burkitt’s Lymphoma
Endemic Burkitt’s
– African type, head and neck,
jaw
– 95 % chance of EBV
Sporadic Burkitt’s
– Abdomen
– 15-20 % chance of EBV
Treatment- Early diagnosis,
surgery, chemotherapy, Tumor
lysis, Treatment based on
stage and histology.
Immunotherapy: Anti-CD 20
monoclonal antibody;
(Rituximab)
Prognosis: Stage Overall 70 %
cure rate, early 85 %.
Case
5 yr old boy with
progressive vomiting,
headache, unsteady
gait and diplopia for 4
weeks. MRI shows a
contrast enhancing
tumor in the 4th
ventricle with
obstructive
hydrocephalus.
Medulloblastoma
- most common CNS tumor
– Trt: Resection, Craniospinal RT, Chemo for
incompletely resected tumor and infants to
permit smaller RT dose and recurrence.
– Prognosis: Age, large size, degree of
resection, dissemination, histology.
Brain Tumors
20% of all malignancies in children
Age 3-7 years
Most often infratentorial
– cerebellar and hemispheric astrocytoma, medulloblastoma,
brain stem gliomas, Craniopharyngiomas.
Sx: Persistent vomiting, headache, gait imbalance,
diplopia, ataxia, vision loss, school deterioration, growth
deceleration
Inherited Genetic disorders Associated:
– Neurofibromatosis, Tuberous sclerosis, Von-Hippel-Lindau
disease, Li-Fraumeni (glioma), Turcot syndrome
A 13 year old female comes with
complaints of headache off and on for the
past 2 months. Of significance, is that her
shoe size has not changed for the past 3
years. She is Tanner stage 1.
CT Scan shows a midline calcification in
the brain.
What do you think is the diagnosis?
Observe the relatively homogeneous and cystic mass arising from the
sella turcica and extending superiorly and posteriorly with compression
of normal regional structures. Note that the lesion is sharply demarcated
and smoothly contoured. Craniopharygioma
Wilms Tumor
An 18-month-old girl is being evaluated because her
mother thinks her abdomen seems “full.” Physical
examination reveals an abdominal mass.
Ultrasonography identifies a solid renal mass. At
surgery, a stage I Wilms tumor is found.
This child’s chance of 4-year survival is CLOSEST to:
A.
B.
C.
D.
E.
30%
45%
60%
75%
95%
CT Scan -Wilms Tumor
Wilms Tumor
Associations: WAGR (Wilms, Aniridia, GU
anomalies, MR)
– Beckwith-Weidemann syndrome- organomegaly,
Hemihypertrophy, omphalocoele)
(chr 11p15.5 gene deletion)
3-5 % risk of WT (general population 8.5/mill)
– Denys-Drash: Pseudohermaphroditism, nephropathy
– Perlman syndrome: Macrocephaly, macrosomia
Do US , UA q 3-4 months
Wilms Tumor
Histology: favorable(FH) vs unfavorable
(UH)
Staging: I-local, II-excised, III-residual, IVmetastases, V -bilateral
Treatment: Nephrectomy, Chemo-all, St III-2 drugs-18 weeks, St III-IV- 3 drugs+ RT
Prognosis:
– FH: > 90% at 2 years
– UH: < 60% at 2 years
Question
A 9 year old previously healthy girl manifests
progressive painless proptosis and decreased
visual acuity of the left eye during a 2 month
period. The most likely diagnosis is
1.
2.
3.
4.
5.
Pseudotumor of the orbit
Trichinosis
Retinoblastoma
Rhabdomyosarcoma
Orbital cellulitis
Rhabdomyosarcoma
7 % of all childhood cancers
Painless non tender mass, 60% under age 6
Sites: head & neck, GU, Extremities, mets lungs.
Majority sporadic, associations: B-W, Li Fraumeni, NF 1
Types:
– Embryonal 70%, better prognosis
– Alveolar 30 %, trunk, worse prognosis
Treatment: Surgery, Chemo, local control RT
Results:
– 85 % good risk
– 30 % metastatic disease
Mass
The mother of a 22-monthold boy reports that he has
been fussy and tired.
Findings on physical
examination confirm the
presence of a nontender rt
upper quadrant mass.
Bilateral periorbital
ecchymoses also are noted.
Of the following, the MOST
likely cause for these
findings is
A. multicystic kidney
disease
B. neuroblastoma
C. non-Hodgkin lymphoma
D. Hepatoblastoma
E. Wilms tumor
Neuroblastoma
The mother of a 22-month-old boy reports that he has
been fussy and tired. Findings on physical examination
confirm the presence of a nontender left upper quadrant
mass. Bilateral periorbital ecchymoses also are noted.
Of the following, the MOST likely cause for these
findings is
A.
B.
C.
D.
E.
multicystic kidney disease
neuroblastoma
non-Hodgkin lymphoma
Hepatoblastoma
Wilms tumor
Neuroblastoma
Most common extra-cranial solid tumor
Most common cancer in the first year of life
Frequent in <4 years, 97 % by 10 years
Most commonly diagnosed as Stage III or IV
Dx: biopsy or BM plus urine for VMA, HVA
Metastatic- orbital discoloration, bone pain
Prognosis: Stage
– Better in age < 1 year, low stage, Shimada
classification (histology), high DNA index.
– Worse with N-myc oncogene amplification and tumor
diploidy (DNA index 1), Higher LDH, Ferritin, age >1.
Neuroblastoma
Low risk:
– Surgery alone; >95 % 5 year survival
Intermediate risk:
– Surgery and Chemo; 80-90 % 5 year survival
High risk:
– Induction chemo, surgery, Chemo with autologous
transplant, RT, Biologic therapy
– 30 % 5 year survival
Stage IVs-Localized Prim tumor with spread to skin,
liver and/or bone marrow- Minimal therapy.
A 16 year old male comes in because he
fell in the supermarket.
P/E shows a small painless mass on the
medial aspect of the knee.
X ray shows a fracture and a lytic sunburst
pattern. (periosteal elevation)
What is your diagnosis?
What would you do next?
Osteogenic SarcomaX ray and MRI
Osteogenic Sarcoma
MRI, Bone scan, Biopsy, CT Chest.
Peak incidence- 2nd decade
Predisposition: Hereditary retinoblastomas, LiFraumeni, Pagets, RT, Alkylating agents
60 % near the knee (Metaphyses of long bones)
History of fall, pain common Sx, mass, no
systemic Sx.
Treatment: Open biopsy, Sperm banking, Neoadjuvant Chemotherapy, limb preserving
surgery.
A 16 year old Caucasian
female comes with complaints
of chest pain and difficulty
breathing for the past one
week. She has had fever, wt
loss over the last 2 months.
She has reduced air entry and
CXR shows a moth eaten
appearance of one of the ribs
and a pleural effusion.
Biopsy is done and is
consistent with Ewings
Sarcoma.
Ewing’s Sarcoma
Seen in Axial bones, flat bones and long bones.
20 % in soft tissue.
Caucasians, Onion skin appearance, Diaphysis
affected.
MRI, CT Chest, Bone scan, Biopsy, BM aspirate
and biopsy( Anemia).
Unique marker: t(11,22) most cases
PNET: Ewing like tumor with neural
differentiation
Treatment:
– Surgery, RT, Neoadjuvant Chemo,
Ewing’s Sarcoma
Retinoblastoma
Presentation:
– Leukocoria (cats eye reflex),Dilated pupil, esotropia, strabismus
Unilateral 75 % (could be hereditary/non)
– 60 % unilateral and non hereditary
– 15 % unilateral and hereditary (RB1 mutation)
Bilateral 25 %
– 25 % are bilateral and hereditary, have RB1 mutation
– Earlier age, 11mos, Can develop in each eye separately
– Higher incidence of sarcoma, melanoma, brain tumors.
10 % of retinoblastoma cases have family history.
But child of parent with the RB1 gene (Chromosome
13q) has a 45 % chance of developing the tumor.
Retinobalstoma
Tumor lysis syndrome
1.
2.
3.
4.
5.
A 12 year old girl with ALL has been started on
Chemotherapy. She had a WBC of 82,000, Hb
9gm, Platelet count of 45,000. Within 12 hours,
she develops findings typical of tumor lysis
syndrome:
Which one of the following depicts it
K high, P high,
LDH normal, Na high
K high, P nl,
LDH high, Na nl
K nl, P high,
LDH high, Na high
K nl, P nl,
LDH high, Na nl
K high, P high,
LDH high, Na nl.
Tumor lysis syndrome
5.
Rapid destruction of cancer cells.
Release of intracellular ions, also Uric
acid, can cause tubular obstruction and
damage.
Treatment: Allopurinol or Rasburicase
early, Hydration, alkalinization, diuretic
therapy,
Chemotherapy-Side effects
Anthracyclines: Cardiomyopathy
Vincristine: foot drop, neurological
Cisplatinum: kidney, deafness
Methotrexate, 6MP: Liver toxicity
Bleomycin: Pulmonary fibrosis
Asparaginase: Pancreatitis
Cyclophosphamaide: Hemorrhagic cystitis
– (MESNA, Uroprotector)
Fever, Neutropenia
Single most important risk factor: ANC
Organisms: Gram negative, Staph epi in
catheter patients
Medication: Broad spectrum 3rd generation
antibiotics
Anti-fungal after 4 days
Examine patient thoroughly
Late effects
A 16-year-old girl, diagnosed at 8 years of age as having
Hodgkins disease, completed therapy with Involved field
RT and chemotherapy. She now develops petechiae,
purpura, LN, HSM. Lab include: plt 12,000/mm³; Hb 8.0
gm/dL; and WBC 13,000/mm³.
The MOST likely explanation for these findings is
A. acute myeloid leukemia as a second malignancy
B. disseminated varicella
C. drug-induced immune thrombocytopenic purpura
D. late-onset aplastic anemia due to chemotherapy
E. viral-induced immune thrombocytopenic purpura
Late effects
1.
2.
3.
4.
5.
You are evaluating a 9 year old child for short
stature. She was treated at 3 yrs of age for
ALL, received cranial RT. Her height is < 5th
percentile and she is Tanner stage I. Of the
following , the test MOST likely to be abnormal
is measurement of
Estradiol
Follicle stimulating hormone
Gonadotropin releasing hormone
Growth hormone
Thyroid stimulating hormone
Late effects of cancer therapy
RT:

Hypothalamic pituitary axis is impaired;
central hypothyroid and Adrenal insuff.

RT doses higher in brain tumor

GH is dose sensitive to the effects of RT

Age related: < 5 years susceptible

Panhypopit with higher doses

ovarian failure with RT
Chemotherapy
A 16 year old boy is receiving chemo for
rhabdomyosarcoma. The treatment involves
one year of repeated cycles of Vincristine,
Actinimycin-D and Cyclophosphamide.
The most likely endocrinologic late effect of this
therapy is
1.
2.
3.
4.
5.
Growth hormone deficiency
Hypothyroidism
Impotence
Infertility
Osteoporosis
Chemotherapy effects
Infertility
Chemotherapy with alkylating agents
Females,less effects than males; normal
puberty, early menopause.
Males; irreversible gonadal toxicity and
sterility with azospermia. Puberty usually
not affected (leydig cells)
Transplant
The most consistent finding observed in
nearly all large cooperative group studies
that have tested matched family donor
hematopoietic stem cell transplantation
(HSCT) for children with AML is:
1.HSCT reduces disease-free survival
2.HSCT improves disease-free survival
3.HSCT improves event-free survival
4.HSCT improves overall survival
Transplant
The most common reason for the failure
of hematopoietic stem cell
transplantation is:
1.
2.
3.
4.
5.
Veno-occlusive disease of the liver
Disease recurrence
Infection
Graft vs. host disease
Graft rejection
GVHD ( Graft vs Host disease)
True statements include all except:
1.
2.
3.
4.
5.
It is the reaction of the donor lymphocytes
against the host.
Acute GVHD starts within the first 100 days
and chronic is after 100 days.
Affects the skin, liver and GI tract
Irradiation of blood products does not help
Complete HLA matching prevents GVHD
Germ cell tumors
2-3 % of Pediatric malignancies
Teratomas arise from endoderm,
ectoderm and mesoderm
Markers:
– Endodermal sinus tumors –Alpha feto protein
– Embryonal Ca, Choriocarcinoma- HCG
Mature teratomas- excision only
Immature Teratomas: Surgery + Chemo
Other topics- do read
Histiocytosis
Storage disorders
GOOD LUCK