Download B2B Peds Hematoloty Oncology

Back to Basics:
Pediatric Hematology/Oncology
Review
Lesleigh Abbott MD FRCPC
Children’s Hospital of Eastern Ontario
March 22, 2017
• No conflicts of interest to declare
Question
• You are called to the ER to see a
2yr old girl with a large
abdominal mass palpable on
exam. She is previously well.
• She has some respiratory distress.
Her uric acid is 150.
• She has not been feeding well
and is irritable.
Objectives
• Key messages of pediatric
hematology/oncology for your exam
Childhood Cancers
• Risk factors
– Chromosomal syndromes
– T21
• ~850 new diagnoses per year
– Prior malignancy
in Canada
– Mostly treatment related
– ~85% of children will
achieve long term survival
– Neurocutaneous syndromes
• Incidence relatively stable
– NF1, Tuberous sclerosis
since 1985
– Immunodeficiency syndromes:
• Causes: no absolute known
Association with lymphoma
cause, some known risk
– Ataxia-telangiectasia
factors
– Hereditary cancer syndromes
– Li-Fraumeni Syndrome
– Exposure to radiation, chemical,
biologic agents
35%
Relative incidence rates of childhood cancers
30%
1. Leukemia
25%
2. Brain tumors
20%
3. Lymphoma
15%
4. NBL is the most common
extracranial solid tumor
of childhood
10%
5%
0%
Leuk
Lymph
Brain/S
Soft tis
Wilms
Neurob
Bone
Retino
Germ C
Epith
Other
Principles of Oncology
• Clinical findings…to…diagnosis
– Imaging
– Biopsy
– Pathology
• Staging work up: where is the cancer
– Where does that type of cancer like to go?
• Define stage/Risk group
• Baseline organ function
• Decide on treatment protocol
– Local/systemic control
Important Labs in Oncology
•
•
•
•
CBC with differential and smear
LDH
Tumor markers: Beta-HCG, AFP
K, Ca, PO4, Creatinine, Uric acid
– WHY?
Tumor Lysis Syndrome
Hyperhydration
Hyperphosphatemia
http://www.learnpicu.com/_/rsrc/1467886157441/oncology/tumor-lysis-syndrome/TLS2.png
What do you see?
Lymphadenopathy
• Constitutional symptoms
– Fevers, night sweats, weight loss
• Infectious exposures
– Travel, animals, camping/ticks
• On exam
– Location, size, consistency, fixation, tenderness
– Supraclavicular**always abnormal
– Liver, spleen
Lymphadenopathy
Inflammatory
Neoplastic
• Constitutional symptoms
– Fevers, night sweats, weight loss
Bacterial (TB)
Autoimmune (RA, SLE)
Lymphoma
• Infectious exposures
Viral (EBV,
CMV, HIV)animals,
Drugcamping/ticks
hypersensitivity
Leukemia
– Travel,
• On exam:
Parasitic (toxoplasmosis)
Metastatic cancer
– Location, size, consistency, fixation, tenderness
Infectious
– Supraclavicular**always abnormal
Fungal (histoplasmosis)
– Liver, spleen,
• Investigations:
– CBC, CXR, PPD, viral testing
– Other imaging
– Biopsy
Indications for LN Biopsy
•
•
•
•
•
Hard, firm, rubbery, non-tender
Progressive growth over short period
Failure of antibiotic treatment
Odd locations – supraclavicular
>2cm
Leukemias
Bone marrow testing
Leukemia
Bone Marrow Biopsy
Normal bone marrow
Bone marrow replaced by leukemia
Childhood Leukemias
Aldrich et al. 2006
Acute Lymphoblastic Leukemia
(ALL)
• Most common type of leukemia <18 yrs
• Presentation
– Fever, fatigue, weight loss
– HSM, lymphadenopathy
– Bone Marrow
– CSF, testes, mediastinal mass
• Symptoms due to
– Infiltration of bone marrow
– Decreased production of normal marrow
elements
ALL
• Pathology: B vs. T cell, cytogenetic markers
• Treatment
• Multi-agent chemotherapy with
maintenance phase
– Up to 3.5 years of treatment
• Intrathecal chemotherapy
• Excellent overall survival…because of large
scale international clinical trials
Query patient with new leukemia
• 10 year old with low energy, petechiae, bony
pain, fevers
• Work-up:
– CBC with differential and smear
• See blasts
• Not normal to see blasts in peripheral smear!!
– Leukemia
– GCSF
– Extreme sepsis
– TLS
– Chest x-ray…
Patient with suspected leukemia
Patient with suspected leukemia
Anterior Mediastinum
• T-cell
– Lymphoma
– Leukemia
• Thymus
• Teratoma
• Thyroid
Lymphoma
Lymphoma
Non-Hodgkin’s
Hodgkin’s
60%
40%
Any age
Adolescents
Rare < 2 yrs
Rare < 5 yrs of age
Lymphoma
Hodgkin
Non-Hodgkin
• AYAs and 50+
• Persistent, painless, rubbery
lymphadenopathy
• B symptoms
• Reed-Sternberg cell
• Treatment: chemo +/radiation
• Incidence peak 7-11 yrs
• Rapidly growing +/- distant
mets
• Types
– Lymphoblastic lymphoma
– Burkitt’s
• Endemic (EBV) vs. sporadic
– Diffuse Large B Cell
– Anaplastic Large T Cell
• Chemotherapy
Presentation of Hodgkin Lymphoma
• Plethora, engorgement of face, upper limbs,
dilation of veins
Superior Vena Cava
Mediastinal Syndrome
• SVC – thin-walled, low intra-luminal pressure
• Surrounded by lymph nodes, thymus
• Tumor can compress SVC: venous stasis
• Compression, clotting, edema:
– Minimize tracheal airflow
– Reduce venous return from the head, neck, upper
thorax
Symptoms and Physical Findings in
Patients with mediastinal mass
•
•
•
•
•
•
•
•
Finding
Cough/dyspnea
Wheezing
Pleural Effusion
Pericardial Effusion
Hoarseness
Facial Edema
Chest Pain
%
68
63
50
19
19
12
6
Mediastinal Mass Management
• Emergency!
• Do not lay flat!
• Oxygen, IV access x2
(lower limbs)
• If intubation is required
– Ensure max support,
most skilled intubator
– Consider awake
intubation (no
neuromusc blockade) in
ICU with ECMO available
• Call PICU and Anesthesia
(early!)
• Call Oncology
– Steroids?
– Diagnostic work-up
• Echo
– Rule out
effusion/tamponade
• Careful imaging and biopsy
Question
• 4 year old girl presents with acute onset of
loss of walking
• She’s been incontinent in the last 24 hours
• Next steps:
Oncologic Emergency:
Spinal Cord Compression
 May be initial presentation or
presentation of relapsed/refractory
disease (NB, EWS)
 Acute weakness/paralysis/sensory
findings
 Management
 Emergent imaging
 Steroids
 Emergent Neurosurgical evaluation
Laminectomy vs. Radiation vs. Chemo
Abdominal Masses
Wilms Tumor
Most common primary renal neoplasm of childhood
• 2-5 years of age
• Asymptomatic, unilateral abdominal mass
• Renal symptoms: HTN, hematuria, abdo pain,
vomiting
Mass
• Treatment:
– Surgical with nephrectomy
– Chemotherapy
– +/- radiation
– 90% long term survival
Kidney
Neuroblastoma
• Neural crest cells arising from sympathetic
tissues
• Originate from any site in sympathetic
nervous system
– Adrenal gland most commonly
– Presentation based on location of mass
– Common to have mets at diagnosis
• Treatment can vary
– Observation to….
– Chemo/Rads/Surgery/ Bone marrow transplant/
Targeted therapy
NBL Clinical Presentation
• Asymptomatic mass
• neck
• thorax
• abdomen
• Pelvis
• Spinal Cord Compression
• “Raccoon eyes”
• Hepatomegaly
• Opsoclonus/myoclonus
 Systemic symptoms
 Weight loss
 Irritability
 Fever
 Hypertension
 Intractable diarrhea
(VIP)
 Bone pain
 Limp
 Refusal to walk
 Pallor
 Skin lesions
Sarcomas
Sarcomas
• Bone: mostly teens
– Osteosarcoma
– Ewing Sarcoma
• Soft Tissue: younger
– Rhabdomyosarcoma
– Non-Rhabdo Soft tissue
sarcoma
–Alveolar Soft Part
Sarcoma
–Sinovial Sarcoma
–Desmoid Tumor
• Presentation
– Mass +/-Pain
– X-ray of primary site
– MRI primary site including
lymph node imaging
– Imaging of possible sites of
metastatic disease
– Bone marrows
– PET scan and/or Bone scan
• Treatment
– Local control: radiation
and/or surgery
– Systemic control:
chemotherapy
OS vs. EWS Radiology
Osteosarcoma
• Bone destruction, moth eaten
appearance
• Periosteal reaction: sunburst,
Codman triangle
Ewing Sarcoma
• Onion skinning: splitting or
thickening of cortex by tumor cells
Codman Triangle
Sunburst
Onion Skinning
Osteosarcoma: Survival
What changed at point d?
Treatment: Surgery/Local Control
Rotationplasty
Brain tumors
Neurooncology
• Red flags: signs of increased ICP: morning headache,
vomiting, papilledema
– gait/balance changes, focal deficits
– Seizures
– Endocrine abnormalities
• Associations with neurocutaneous diseases
– Neurofibromatosis, Tuberous Sclerosis
• Classified by location and histology
– Astrocytoma, Medulloblastoma, Ependymoma
• Treatment: depends on location and pathology
– Multimodality: surgery, radiation, chemo
• Late effects: neurocognitive, secondary cancers,
endocrinopathies
Bone Marrow Transplant
Autologous
Allogenic
• Donor
•
•
•
•
Collection of own cells
High dose chemotherapy
Can do 1-4 in a row
Indications:
–
–
–
–
Neuroblastoma
Medulloblastoma
Relapsed solid tumors
Relapsed Hodgkin Lymphoma
– Related, unrelated
• GVHD
• Immune suppression
• Indications:
–
–
–
–
–
Relapsed leukemias
Severe Idiopathic Aplastic Anemia
Sickle Cell Disease, Thalassemia
Congenital immune deficiencies
Metabolics: Hurler’s syndrome
Bone marrow transplant
http://media-2.web.britannica.com/eb-media/16/67716-004-C53DF929.jpg
What else?
• Late effects:
– Surgery: limb, bone, organ removal
– Organ effects: kidney, liver, cardiac
– Growth
– Secondary malignancies
• Targeted therapies
– Limit toxicities
– Sequencing
• PROFYLE study
Hematology
A few reminders in brief…
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
Blood smear
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
Sickle Cell Disease
• Autosomal recessive
– Beta-globin gene mutation
• Causes polymerization of hemoglobin leading
to effects of decreasing blood flow, tissue
hypoxia, leading to acute and chronic damage
https://www.thelondonphysician.com/wp-content/uploads/Risk-Factors-for-Sickle-Cell-Anemia_12.jpg
Sickle Cell
Complications
• Acute
–
–
–
–
–
Stroke
Chest crisis
Vaso occlusive crisis
Aplastic crisis
Priapism
• Chronic
– School performance
– Vasculopathy
– Infections
Sickle Cell Treatment
• Lifelong condition
• Chronic
• Education
• Counseling for reproduction
• Acute crisis
– Fluids, Pain control
– Broad Spectrum Antibiotics
– Straight transfusions vs.
Exchange transfusion
– Oxygen
–
–
–
–
Penicillin prophylaxis
Vaccinations
Hydroxyurea
Chronic transfusion
program
– Transcranial doppler
ultrasounds
– Multidisciplinary clinic
Questions
1) What type of cell is this?
MCQ
1) What is the predominant cell type?
A) Shistocyte
B) Spherocyte
C) Pappenheimer bodies
D) Ringed Sideroblasts
E) Microcytes
2) What is your diagnosis for this type of anemia?
MCQ
2) What is your diagnosis for this type of anemia:
A) G6PD deficiency
B) Thalassemia
C) Sickle Cell Disease
D) Spherocytosis
E) Iron deficiency anemia
MCQ
3) Which is most likely to cause hemolytic
disease of the newborn:
A) Biliary atresia
B) G6PD deficiency
C) Spherocytosis
D) Rh incompatibility
E) ABO incompatibility
MCQ
4) Presentation of ITP often includes:
A) Neutropenia
B) Small Platelets on blood smear
C) Large platelets on blood smear
D) Purpura
E) Lymphadenopathy
MCQ
5) What is the most commonly used treatment
for pediatric ITP?
A) Observation
B) Corticosteroids
C) IVIG
D) Splenectomy
E) Anti-D
MCQ
6) You are seeing a 3 day old baby boy who is
bleeding excessively post circumcision. What
condition are you most concerned to rule out?
A) von Willebrand’s disease
B) Platelet function disorder
C) Factor VIII Deficiency
D) Factor XI Deficiency
E) Factor XIII Deficiency
MCQ
7) Other than a CBC and smear, which of the
following is a work-up for hemolysis?
A)
B)
C)
D)
Smear, Retics, DAT, LDH, Bilirubin, Haptoglobin
Differential, Retics, IAT, LDH, Bilirubin
Smear, Retics, IAT, LDH, Bilirubin, Haptoglobin
Differential, Retics, DAT, LDH, Bilirubin,
Haptoglobin
MCQ
8) 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 acetaminophen
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
Question
9) 15 year old male in respiratory distress with
first episode of wheeze in ER. Resolved with
ventolin and IV methylpred. One week later,
radiologist sees mediastinal mass on CXR.
Name three differential diagnoses.
MCQ
10) The following are causes of microcytic anemia in a
child
A) Folate deficiency
B) B12 deficiency
C) Hypothyroidism
D) Thalassemia
E) Recent blood loss
MCQ
11) You are seeing a 11 year old boy with
lymphadenopathy and a mediastinal mass.
B symptoms refers to:
A) Drenching night sweats, poor sleep, weight loss
B) Drenching night sweats, unexplained fevers, weight loss
C) Poor sleep, unexplained fevers, weight loss
D) Unexplained fever, weight loss, bulk disease
E) Drenching night sweats, unexplained fevers, bulk disease
12) Is this a leukemia blast or a
normal lymphocyte?
13) What is the most common types of
childhood cancer: put in order
of most common to least common
Brain tumours
Lymphomas
Leukemia
Neuroblastoma
Sarcoma
14) Question
• You are called to the ER to see a
2yr old girl with a large
abdominal mass palpable on
exam. She is previously well.
• She has some respiratory distress.
Her uric acid is 150.
• She has not been feeding well
and is irritable.
• DDx: name 3?
Thank-you!
Good luck everyone