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Back to Basics 2015:
Pediatric Hematology/Oncology
April 1, 2015
Lesleigh Abbott MD FRCPC
Children’s Hospital of Eastern Ontario
[email protected]
• No conflicts of interest to declare
Outline
• Pediatric Hematology
• Pediatric Oncology
Hematology
• CBC: WBC, Hemoglobin, Platelets
– Number and morphology (and function)
• MCV: mean corpuscular volume
• MCHC: mean corpuscular hemoglobin concentration
• RDW: red cell distribution width
• Reticulocytes: immature RBCs
• Bleeding/Thrombosis
– PTT
• intrinsic: I, II, V, VII, IX, X, XI, XII
• Mixing study
– PT/INR
• extrinsic: I, II, V, VII, X
Blood smear
Normal Blood Smear
MCQ
The following are causes of microcytic anemia in a child
A) Folate deficiency
B) B12 deficiency
C) Hypothyroidism
D) Thalassemia
E) Recent blood loss
Low Retics
(Inadequate Response)
Anemia
Microcytosis
Normocytic
Macrocytosis
High Retics (Adequate
Response)
Hemolytic disorders
Thalassemia
Recent blood loss
B12 Deficiency
Hemoglobinopathy
Sickle Cell Disease
Chronic
Disease
Malignancy/marrow
infiltration
Folate deficiency
Enzymopathy
G6PD, PK
Iron Deficiency Chronic Renal Failure
Drugs
Membranopathy
spherocytosis, elliptocytosis
Lead
intoxication
Transient
Erythroblastopenia of
Childhood (TEC)
Hypothyroidism
Extrinsic factors
DIC, HUS, TTP, Burns
Sideroblastic
Anemia
Marrow aplasia
Chronic Liver
disease
Immune
autoimmune, isoimmune,drug
HIV
Alcohol
Chronic Inflammatory
disease
Reticulocytosis
Myelodysplasia
Bone marrow
failure syndromes
MCQ
You are seeing 2 year old girl in clinic, well
nourished, but very pale, low energy and picky
eater. Her blood smear shows the following:
Your diagnosis is:
A) Iron deficiency anemia
B) Thalassemia
C) Sickle Cell Disease
D) Spherocytosis
E) G6PD deficiency
MCQ
Which of the following is not the cause of
unconjugated jaundice in a newborn infant
A) Rh incompatibility
B) G6PD deficiency
C) Spherocytosis
D) Biliary atresia
E) ABO incompatibility
Hemolytic Disease of the Newborn
• Alloimmune condition
• IgG of mom pass through the placenta to baby and attacks the
RBCs of baby causing hemolysis
– Anemia and Increased reticulocytes
– Unconjugated hyperbilirubinemia
• Incompatibility of red blood cells
– Rh : Anti-D to Rh Negative Mothers
– ABO: Mom usually type O blood
• Treatment
– For jaundice: phototherapy, exchange transfusion
MCQ
Other than a CBC and smear, which of the
following WOULD NOT be a part of a hemolysis
work-up?
A) AST and ALT
B) Reticuolcytes
C) DAT
D) LDH
E) Bilirubin
Direct Antibody Test or Coombs test
Looking for antibodies attached to red cell surface
Indirect Antibody Testing
Recipient’s antibodies from serum and donor’s blood sample:
cross match and antibody screen
Hemoglobinopathies:
Sickle Cell Disease
• Sickle Cell Disease
– Genetic defect in β-globin genes
– Autosomal recessive
– Red cell sickle under stress (low pO2, dehydration, fever,
acidosis)
• Results in infarction of tissue: spleen, lungs, bone,
brain, digits
– Functional asplenia
• Greatest cause of mortality is infection/sepsis
– Acute Chest syndrome
– Vaso-occlusive crisis
– Aplastic crisis vs. Acute splenic sequestration
– Stroke
– Priapism
MCQ
You are on-call and get a phone call from a patient with Sickle
Cell Disease with a fever in the middle of the night.
What do you do?
A) Advise to take Tylenol
B) If they fell unwell, see their doctor in the morning
C) Go to the closest ER for broad spectrum antibiotics and
possible admission
D) Go to the closest ER for assessment of possible antibiotics
E) Ask the patient why they woke you up and go back to sleep
Sickle Cell Treatment
• Lifelong condition
• Chronic
• Education
• Counseling for reproduction
• Acute crisis
– Fluids, Pain control
– Antibiotics
– Straight transfusions vs.
Exchange transfusion
– Oxygen
–
–
–
–
Penicillin prophylaxis
Vaccinations
Hydroxyurea
Chronic transfusion
program
– Transcranial doppler
ultrasounds
– Multidisciplinary clinic
Hemoglobinopathies
• Hereditary Spherocytosis
– Autosomal Dominant
– Abnormality in RBC membrane proteins (spectrin)
– Most common hereditary hemolytic anemia
– High osmotic fragility
• More prone to physical degradation
– Functional asplenia
– Treatment:
• Supportive care
• Immunization against encapsulated organisms
– Pneumococcus, meningococcus, HiB
G6PD: Glucose-6-Phosphate
Dehydrogenase Deficiency
• Sensitivity of RBC to oxidative stress
• X-linked
• Hemolysis mediated by oxidative stress, drugs,
infection, foods (fava beans)
• Neonatal jaundice
• G6PD assay
• Heinz bodies and bite cells
• Avoid triggers
• Transfuse as necessary
Non-Immune Destruction
• DIC, TTP/HUS, ECMO/Bypass, Sepsis,
Preeclampsia/HELLP syndrome, drug induced
MCQ
• What is the predominant cell type in the last
smear?
A) Shistocyte
B) Spherocyte
C) Pappenheimer bodies
D) Ringed Sideroblasts
E) Microcytes
Non-Immune Thrombocytopenia
HUS: Hemolytic Uremic
Syndrome
• Infants and young children
• Preceding colitis with bloody
diarrhea
• E.coli verotoxin (O157:H7)
• Presentation
• Thrombocytopenia
• Microangiopathic Hemolytic
Anemia
• Renal failure
• Management:
– Dialysis
– Supportive care
TTP: Thrombotic
Thrombocytopenic Purpura
• Classic diagnostic pentad
– Microangiopathic hemolytic
anemia
– Thrombocytopenia
– Renal manifestations
– Fever
– Neurological findings
• Management: Plasmapheresis
• Steroids, Rituximab
• Decreased ADAMTS13
– With or without associated
antibody
– Breaks down vWF large multimers
MCQ
The following are lab findings for TTP except:
A) Schistocytes and helmet cells on smear
B) Elevated LDH
C) Reticulocytosis
D) DAT Positive
E) Normal coagulation studies
ITP: Immune Thrombocytopenia
Purpura
• Most common cause of thrombocytopenia in
childhood
• Peak age: 2-6 years
• Caused by antibodies that bind to platelet
membranes
– Leads to splenic uptake and destruction
MCQ
Presentation of ITP includes:
A) Neutropenia
B) Small Platelets on blood smear
C) Anemia
D) Lymphadenopathy
E) Epistaxis
MCQ
All are treatments for ITP, except:
A) Observation
B) Corticosteroids
C) IVIG
D) Dapsone
E) Anti-D
MCQ
The inheritance pattern of hemophilia A and B is:
A) X-linked
B) Autosomal Recessive
C) Autosomal Dominant
D) Autosomal Dominant with incomplete
penetrance
Bleeding Disorders: Hemophilia
•
•
•
•
•
Most common inherited bleeding disorder
X-linked
Hemophilia A (F VIII deficiency)
Hemophilia B (F IX deficiency)
Presentation
– Bleeding: joints, muscles, GU tract, excessive post trauma
• Labs: Prolonged PTT
– No change with mixing study
– Low factor levels
• Treatment
– DDAVP
– Recombinant factor concentrate
• Inhibitor development
– Supportive
MCQ
The features of von Willebrand factor includes
all of the following except:
A) platelet adhesion
B) carrier of F VIII
C) exists as circulating multimers
D) vitamin K dependent factor
E) acute phase reactant
Von Willebrand’s Disease
• Most common bleeding disorder
• Symptoms: mostly mucocutaneous bleeding
• Treatment:
– Increase vWF: DDAVP, Antifibrinolytics, vWF
concentrates
• Type 1: mild quantitative defect
– Decreased amount of vWF
• Type 2: qualitative defect
– Dysfunctional vWF
• Type 3: severe total quantitative defect
– No vWF produced
Lymphadenopathy
• Constitutional symptoms
– Fevers, night sweats, weight loss
• Infectious exposures
– Travel, animals, camping/ticks
• On exam:
– Location, size, consistency, fixation, tenderness
– Liver, spleen,
• Investigations:
– CBC, CXR, PPD,Inflammatory
viral testing, otherNeoplastic
imaging, biopsy
Infectious
Bacterial (TB)
Autoimmune (RA, SLE)
Lymphoma
Viral (EBV, CMV, HIV)
Drug hypersensitivity
Leukemia
Parasitic (toxoplasmosis)
Fungal (histoplasmosis)
Metastatic cancer
Childhood Cancers
• ~850 new diagnoses per year in Canada
– ~85% of children will achieve long term survival
• Incidence relatively stable since 1985
• Causes: no absolute known cause, risk factors
–
–
–
–
Chromosomal syndromes: T21
Prior malignancy
Neurocutaneous syndromes: NF1, Tuberous sclerosis
Immunodeficiency syndromes
– Association with lymphoma
– Family history
– Li-Fraumeni Syndrome
– Exposure to radiation, chemical, biologic agents
Important Labs in Oncology
• CBC with differential and smear…
• K, Ca, PO4, Creatinine
– WHY?
•
•
•
•
LDH
Tumour markers: Beta-HCG, AFP
Ferritin, ESR
Looking for chemo side effects
Treatment:
Chemotherapy, Radiation, Surgery
• Cytotoxic, targeted, combination….
• Special considerations in children:
– Long term toxicity
• Growth
• Development/Neurocognitive
• Puberty/Fertility
• Bone health
• Physical and mental health
• End organ disease
–Cardiac, Lung, Renal, Liver…
MCQ
What is the most common type of childhood
cancer?
A) Lymphoma
B) Leukemia
C) Brain Tumours
D) Wilms’ Tumour
E) Sarcomas
Most common types of childhood cancer
1) Leukemia
2) Brain tumours
3) Lymphomas
4) Neuroblastoma
5) Wilms’ tumour
6) Sarcoma
Leukemia
• Acute Lymphoblastic Leukemia (ALL)
• Most common type of leukemia <18 yrs old
• Presentation:
• Bone Marrow, CSF, testicular
• Hepatosplenomegaly, lymphandenopathy
• Fever, fatigue. Weight loss
• Mediastinal mass
• Risk group: Age and WBC
• Cytogenetics, ploidy, response (MRD)
• Treatment
• Multiagent chemotherapy
• Intrathecal chemotherapy
• Craniospinal radiation
• Excellent overall survival…because of clinical trials
• BCR-Abl: Philadelphia chromosomal translocation
Brain Tumours
• Red flags: morning headache, vomiting, papilledema,
gait/balance changes, focal deficits
• Associations with neurocutaneous diseases
– Neurofibromatosis, Tuberous Sclerosis
• Classified by location and histology
• Investigations: Head/Spine MRI
• Treatment depends on location and pathology
– Don’t always need biopsy if characteristic image
findings
MCQ
You are seeing a 11 year old boy with
lymphadenopathy and fever. B symptoms refer to
all of the following except:
A) Drenching night sweats
B) Unexplained fevers
C) Poor sleep
E) Weight loss
Lymphoma
Hodgkin
• Ages 15-34yrs and 50+
• Persistent, painless, rubbery
lymphadenopathy
• B symptoms
• Reed-Sternberg cell
• Treatment: chemotherapy
and radiation based on
response and risk group
Non-Hodgkin
• Incidence peak 7-11 yrs
• Rapidly growing with distant
mets
• Types
– Lymphoblastic lymphoma
– Burkitt’s
• Endemic (EBV) vs. sporadic
– Diffuse large B cell
– Anaplastic large T cell
• Primary treatment with
chemotherapy
MCQ
This patient is in your office
and you feel an abdominal
mass. Next step:
A) Observation
B) Ultrasound of abdomen
C) Surgical consultation
D) MRI abdomen
Abdominal Mass
Wilms’ Tumour
• Most common primary renal
neoplasm of childhood
• 2-5 years of age
• Asymptomatic, unilateral
abdominal mass
• Renal symptoms: HTN,
hematuria, abdo pain, vomiting
• Treatment:
– Surgical with nephrectomy
– Chemotherapy +/- radiation
– 90% long term survival
Neuroblastoma
• Neural crest cells arising from
sympathetic tissues
• Originate from any site in
sympathetic nervous system
• Presentation based on location
of mass
• Common to have mets
• Treatment can vary
• Observation to….
• Chemo/Rads/Surgery/
Bone marrow transplant/
Targeted therapy
Sarcomas
• Bone: mostly teens
– Osteosarcoma
– Ewing Sarcoma
• Soft Tissue: younger
– Rhabdomyosarcoma
• Presentation
– Mass
– +/-Pain
– X-ray of primary site
• Treatment
– Local control: radiation and/or surgery
– Systemic control: chemotherapy
Osteosarcoma: Survival
What changed at point d?
Treatment: Surgery/Local Control
Rotationplasty
MCQ
You are seeing a child with lymphadenopathy
and fever. What is your most important first test
after your physical exam?
A) Chest X-ray
B) ALT and AST
C) Creatinine and BUN
D) CBC with differential
E) Bilirubin and albumin
MCQ
It’s July 1st…you are seeing a teenager in the ER
with Hemophilia A and a swollen knee. What
will you give for treatment?
A) Recombinant factor VIII concentrate
B) Cryoprecipitate
C) ASA
D) Platelet transfusion
E) FFP
Thank-you!
Good luck everyone
Lesleigh Abbott
[email protected]