Pediatric Board Review Course Pediatric Hematology/Oncology

1
Pediatric Board Review CoursePediatric
Hematology/Oncology

• Kusum Viswanathan, MD
• Chair, Department of Pediatrics
• Director, Divn of Pediatric Hematology/Oncology
• Brookdale Univ Hospital and Medical Center

2
Question

• 6 week old term infant referred 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

3
Most likely explanation for the anemia

1. G 6 PD deficiency
2. Hereditary spherocytosis
3. Physiologic anemia
4. ABO incompatibilty
5. Rh hemolytic disease

4
Newborn anemia- important

• Hemoglobin at birth is 17 g/dl, MCV over 100.
• Falls to 11-12 by 6 weeks of age- nadir of
  physiologic anemia
• Anemia at birth could be
• 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

5
The treatment of choice for alloimune neonatal
thrombocytopenia is

1. random platelet transfusion
2. IVIG
3. Steroids
4. Exchange transfusion
5. Washed maternal platelets

6
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 lt 50,00 have 1 risk of
  ICH.
• IVIG to mother, Fetal platelet counts, C sec, US,
  IVGG to baby
• Allo or Iso-Immune Normal platelet count in
  mother
• Similar to Rh disease PL A1 antigen/ Zw-a
  negative mother.
• 97 of population is PL A1 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
• Mothers washed (PLA1 neg) platelets IVIG
  Ultrasound Steroids

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Kasabach- Merritt, TAR
8
15 months old girl presented in ER with h/o URI,
and scattered petechiae and ecchymoses over the
body and lower extremities.
Physical exam normal, no hepatosplenomegaly.
WBC-14,000, Hb 12.8, Plts-5,000, Diff Normal -
Next step

1. perform a bone marrow aspirate to confirm the
   diagnosis
2. Non-accidental injury skeletal survey to rule
   out bony fractures
3. treatment with either IVIG or anti-D
4. Administer platelet transfusion

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Acute ITP

• Usually acute onset immune mediated post viral
• Peak 2-5 years of age,
• PE no lymphadenopathy (LN), hepatosplenomegaly.
• CBC- other cell lines normal, large plts on smear
• Treat if pltlt 10,000 or wet ITP,
• Treat- IVIG best response, 48-72 hours blocks Fc
  receptors,SE
• Anti-D (WInRho)- Rh ,hemolysis, quick response
• Steroids good response, block phagocytosis,
  reduces antibodies, SE, inexpensive, need BM
• BM- Increased megakaryocytes, otherwise normal
• Chronic- If gt6 months, FgtM, older, unpredictable
  prognosis

10
Petechiae, HSP
11
A 2 year old boy presents for evaluation of a
chronic pruritic eruption. H/o recurrent
epistaxis, otitis media, and pneumonia
P/E reveals erythematous, slightly scaling
patches on the trunk and in the antecubital and
popliteal fossae. Petechiae too- most suggestive
of

1. Acrodermatitis enteropathica
2. Ataxia telangiectasia
3. Atopic dermatitis
4. Langerhans cell histiocytosis
5. Wiskott-Aldrich syndrome

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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,
  platelet dysfunction)

13
Platelet function defects

• Normal platelet number
• Abnormal aggregation
• Glanzmann thrombasthenia--- AR, Bleeding
  disorder, check h/o consanguinity
• afibrinogenemia
• Abnormal adhesion- Bernard-Soulier, VWD
• Ineffective Thrombopoiesis
• MayHegglin Anomaly (Large platelets)
• Disorders of Secretion Storage pool, gray
  platelet syndrome
• Hermansky Pudlak Syndrome
• AR, Decreased dense granules, In Puerto Ricans
• Oculocutaneous albinism

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Thrombocytosis

• H- Hemorrhage, Hereditary Asplenia, Down
  myeloprol.
• I- Infections, Kawasaki, ImmuneGVH, Nephrotic
  syndrome
• P- Polycythemia vera, Myeloproliferative,
  Essential
• L- Leukemia (CML)
• A- Anemia,- Iron, Vit E deficiency,
  Sideroblastic
• T- Tumors
• E- Epinephrine, Steroids
• L- Lymphoma, Hodgkins
• E- Exercise
• T- Trauma, Fractures
• S- Splenectomy

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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??

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Reticulocyte count

• Normal/Low- reduced production
• Iron deficiency anemia- MCV will be low
• ALL (leukemia)- other findings, LN, HSM
• Diamond Blackfan anemia-
• TEC Over 1 year of age, Pallor, transient rbc
  production failure, recovers, MCV and Hb F high
  during recovery, rbc transfusion, rbc ADA normal
  .

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Normal smear
18
A 2 month old girl with a history of ventricular
septal defect and horseshoe kidney presents for a
health maintenance visit.

• Her parents are concerned that she is not feeding
  well, appearing to become tired soon after
  beginning to breastfeed. She is tachycardic and
  appears pale. Her hemoglobin level is 3.8 g/dL.
  Peripheral smear reveals macrocytic red blood
  cells. The bone marrow aspirate shows normal
  cellularity of the marrow with markedly decreased
  erythroid precursors. 
• Which of the following findings is most likely to
  be identified during additional physical
  examination of this patient?
• Multiple superficial hemangiomas
• Cutis aplasia
• Bifid thumbs
• Speckled white rings in the periphery of the iris
• Posterior parietal hair whorl

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Microcytic anemia is a characteristic laboratory
abnormality of all listed diseases except

1. Iron deficiency
2. Lead poisoning
3. Sickle cell disease
4. Thalassemia trait

20
Microcytic anemia
21
Question

• A blood smear taken from a toddler shows
  microcytic hypochromic anemia. Iron
  supplementation therapy is started. When will
  the reticulocyte response be at maximum?
• a. 1-2 days
• b. 5-7 days
• c. 14-21 days
• d. 3-4 weeks
• e. about 6 weeks

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Iron deficiency questions

• Low MCV, low MCHC, low retic, RDW can be normal,
  Low Iron, Incr TIBC, Transferrin low, Ferritin
  low
• Causes Inadequate dietary intake
• Toddlers, too much milk, less solids, Breast fed
  need iron supplements
• 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.

23
Question- Beta Thalassemia

• 3 year old comes for a routine check and found to
  be anemic. P/E Normal. CBC Hb 8.9, MCV 58, Iron
  levels are normal. Hemoglobin electrophoresis is
  done and shows Beta Thalassemia trait. All are
  true except
• The MCV is always low
• Fetal hemoglobin is lt 2
• Hemoglobin A 2 is gt 3.5
• Does not respond to Iron
• RDW is usually normal

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Beta 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 or Delta-
  Increased Hb F and A2.
• Smear abnormalities significant even with MILD
  anemia.

• Anemia
• Low MCV, normal RDW, normal retic
• Smear shows aniso and poikulocytosis, target
  cells, microcytes, misshapen cells, basophilic
  stippling
• Hb Electrophoresis Increased Hb A2 and/or F.
• Normal iron studies, no response to iron

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Beta Thalassemia Major

• No production of Beta chains- Chromosome 11
• 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

26
Question

• 4 year old male with no complaints. Routine CBC
  showed a Hb9.8, MCV 62, RDW 12.5 , Retic 0.2,
  Normal Iron studies, Hemoglobin electrophoresis
  was normal with normal Hb A2 and Hb F. You
  suspect Alpha Thalassemia. All of the statements
  are true except
• It is carried on 4 alleles
• The severe form is Hydrops fetalis
• Hemoglobin H disease occurs when 3 alleles are
  affected
• Diagnosed by newborn screening when a fast
  moving hemoglobin is noted.
• Fast moving hemoglobin is made up of a hemoglobin
  with 4 beta chains

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Thalassemia- Alpha

• Reduced Alpha chains
• 4 types- carried on 4 allelles. (xx/xx)
• One absent- Silent carrier (x-/xx)
• 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 chains form Hb Barts-
  FAST moving Hb on Newborn screening

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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??

29
Question

• A previously well African-American 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.
• SMEAR

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An African-Am child visited Africa received
malaria prophylaxis. He has

1. Hereditary spherocytosis
2. Sickle cell disease
3. Hepatitis
4. G6PD deficiency

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Reticulocyte count- Increased

• Hemolysis
• Intrinsic-
• Membrane defects-Hereditary spherocytosis (HS)
• Enzyme-G 6 PD deficiency
• Hemoglobinopathies
• Extrinsic- AIHA (Auto-immune hemolytic anemia),
  DIC, Intravascular hemolysis
• Loss
• Blood loss

32
Children with hereditary spherocytosis have all
of the listed conditions except

1. positive Direct Coombs
2. splenomegaly, gallbladder stones
3. abnormalities in spectrin and /or ankyrin
4. increased MCHC
5. abnormal osmotic fragility test.

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Spherocytes

• Spherocytes
• Nucleated rbc
• Coombs-AIHA
• Osmotic fragility-HS

34
HS- with severe anemia

• A 6 year old girl who has hereditary
  spherocytosis presents with a 1 week history of
  fever. Physical examination reveals 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 girls present illness is
  infection with
• Coxsackie virus
• Parvovirus B19
• Epstein-Barr virus
• Hepatitis A virus
• Influenza A virus

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HS- with severe anemia

1. Coxsackie virus
2. Parvovirus B19
3. Epstein-Barr virus
4. Hepatitis A virus
5. Influenza A virus

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Newborn Screening Questions

• You get a call from a frantic parent because she
  received a letter from the State regarding her
  babys 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

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Sickle cell Questions

• 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 gt75 .
• Penicillin daily until age 5.
• Prevention of pneumococcal infections-asplenic.
• PPV (Pnu-23) age 2, 5
• Meningococcal vaccine early two doses and every 5
  years.
• Folic acid daily

38
Sickle cell questions

• Vaso-occlusive crisis
• New infant born in another country presenting
  with swollen hands---Dactylitis
• Aplastic crisis
• low Hb, low retic, Secondary to Parvovirus B 19
  infection.
• Splenic sequestration crisis
• Sudden enlargement of the spleen in SS or older
  SC patient
• Rx- Transfuse
• Teach spleen palpation
• Splenectomy

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The mother of a 10 month old baby with SS disease
asks you about prognostic indicators. All of the
following indicate likelihood of more severe
disease except

1. High WBC
2. Associated alpha thalassemia trait
3. Low hemoglobin
4. Repeated episodes of dactylitis

40
Sickle cell Acute Chest Syndrome

• True statements include all except
• 1. Presents with a new infiltrate on X-ray
• 2. Due to infarction, infection, BM fat embolism
• 3. Treat with antibiotics to cover pneumococcus,
  Mycoplasma, Chlamydia
• 4. Treat with bronchodilator, Incentive
  spirometry, transfusion, Steroids
  (controversial).
• 5. Intensive hydration is important

41
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

42
According to the STOP protocol all children with
abnormal TCD require enrollment in
hypertransfusion protocol till (choose one)

1. Repeat TCD is normal
2. Continue indefinitely
3. the child reaches 18 years
4. MRA/MRI are reported normal

43
Sickle cell and Stroke Questions

• Affects 10 of patients
• Infarctive stroke (younger patients)
• 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 (CBFgt 200cm/sec)
• Reversal of CBF velocity is not sufficient to
  stop transfusion therapy. (STOP II)

44
Sickle cell and Hydroxyurea

• FDA approved for adults
• Studies in children demonstrated efficacy and
  safety
• Increases hemoglobin F level
• Increases hemoglobin
• Decreases WBC ancillary effect
• Reduces number of ACS, VOC
• Hydroxyurea is recommended by the hematologist
  for patients who have recurrent vaso-occlusive
  crises, acute chest syndrome.

45
A healthy 5 year old boy- 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. Most appropriate step is

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

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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

47
Abnormal Bleeding

• Epistaxis unrelieved by 15 minutes of pressure,
  both nostrils, requiring an ER visit, documented
  drop of hemoglobin.
• Menstrual periods( amount, pads, duration)
• Bleeding after procedures (circumcision, dental
  extractions, T and A-delayed bleed)
• Ecchymoses/bruising inconsistent with the degree
  of trauma

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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)

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Lab studies(What do they measure?)

• CBC and Peripheral smear
• PT, INR and PTT
• PT - Factor VII, common pathway
• PTT- Factor VIII, IX, XI, XII, common pathway
• Mixing studies (Inhibitors and deficiency)
• Specific coagulation factor assays

50
Coagulation cascade
51
Questions on 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.

52
A healthy 2-day-old boy born at term undergoes
circumcision.
Bleeding noted at the site 10 hours after the
procedure and increased steadily over the past 4
hours. Findings on exam are unremarkable except
for bleeding along 2 to 3 mm of the surgical
site no petechiae or purpura.

1. Disseminated intravascular coagulation
2. Factor VIII deficiency hemophilia
3. Immune thrombocytopenic purpura
4. Neonatal alloimmune thrombocytopenia
5. Von Willebrand disease

53
Hemophilia Questions

• Factor VIII deficiency (Hemophilia A)-85
• X-linked recessive, Carriers asymptomatic
• Severelt1, Moderate 1-5, Mild 6-30
• Treat Recombinant Factor VIII 1unit/kg raises
  factor level by 2 . Half life 12 hrs. Joint
  bleeds need100, muscle bleeds 50 .
• DDAVP for mild cases.
• 30 develop inhibitors after infusions with
  concentrate (Approx 50 infusions)
• Factor IX deficiency (Hemophilia B)
• X-linked recessive, less common

54
A patient with Hemophilia A has asked you about
the possibility of his children being affected by
the disease.
The partner is normal.

1. There is a 50 chance that his sons will have
   the disease.
2. There is a 50 chance that his daughters will be
   carriers
3. There is a 100 chance that his sons will have
   the disease
4. There is a 100 chance that his daughters will
   be carriers

55
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

56
Questions on Von Willebrands Disease1-2 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
• Rx-Plasma derived VWF containing concentrates

57
Thrombophilia

• 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

58
The most common cause of familial predisposition
to thrombosis is

1. Hemophilia antibodies
2. Protein C deficiency
3. Protein S deficiency
4. Factor V Leiden mutation
5. Antithrombin III deficiency

59
Tests performed on donated units of blood

1. all units are tested only for hepatitis B and C
2. all units are tested only for human
   immuno-deficiency virus (HIV)
3. all units are tested for HIV, hepatitis B, and
   hepatitis C
4. all units are tested for HIV, hepatitis B,
   hepatitis C, sickle cell trait, cytomegalovirus,
   and Epstein-Barr virus
5. only units obtained from donors who have one or
   more risk factors are screened for HIV, all units
   are tested only for hepatitis B and C

60
Questions on Transfusion

• CMV negative- give leukocyte reduced.
• Irradiated products- To prevent GVHD
• Washed cells-
• Phenotype matched
• To prevent allo-immunization
• Sickle negative

61
CANCER IN CHILDREN

• Distribution-All ages

62
A 6-year-old girl has aching in her arms, legs,
and back for gt 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.

1. ALL
2. Aplastic anemia
3. Gaucher disease
4. lead poisoning
5. Multifocal osteomyelitis

63
ALL (Acute Lymphoblastic leukemia)

• 75 of all Leukemias
• Can present with generalized bone pain, fatigue
• Bruising, nose bleeds
• Unusual fevers, infection
• Lymphadenopathy, hepatosplenomegaly

64
ALL- Should know (Acute Lymphoblastic leukemia)

• Abnormal to see blasts in the peripheral smear
• Diagnosis gt25 blasts in the BM.
• Normal marrow has lt 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, Kostmanns, Monosomy 7, DBA,
  Fanconi anemia, 20 risk in twin if age lt5yrs

65
ALL Treatment

• Induction 4-6 weeks,
• Consolidation /delayed Intensification
• 6-12 months rotating drugs.
• Maintenance Daily oral 6-MP, weekly MTX,
  Monthly pulses of Vincristine and Steroid.
• Imatinib mesylate-Tyrosine Kinase Inhibitor- Ph
  Chromosome positive patients
• CNS prophylaxis Intrathecal chemo
• CNS Therapy RT Intensive systemic chemo
• Testicular disease RT
• SANCTUARY- CNS, Testis

66
ALL- Prognosis

• Prognosis
• WBC, Age, Cytogenetics
• good if hyperdiploidy (gt50),trisomy 4,10,17,
  t(12,21)
• Bad if hypodiploid, Ph. chrom t (9,22),t(4,11),
  t(8,14)
• Immunophenotype Pre-B good, B and T-worse
• Early response, Minimal residual disease (MRD)
• Infants 50 survival
• Early relapse is a poor sign

67
Down Syndrome and Leukemia

• 10-20 fold increase
• DS 400 fold Increase in M7 AML
• Superior response to Rx of AML
• Transient Myeloproliferative disorder in newborn
  which resolves within 3 months.

68
Acute Myeloid Leukemia (AML)

• 20 of all leukemias
• Increased incidence in lt 1 year of age
• Higher incidence
• Downs, Fanconi, Bloom, DBA, Kostmann,
  Neurofibromatosis I, Schwachman-Diamond
• Chloromas solid collection in bone/soft tissues
• Types M0-M7, commonest M2
• DIC in M3- (Promyelocytic- APML)
• M7- Downs syndrome

69
Question Hodgkins

• 16 year old male presents with a painless
  swelling in the supraclavicular region. Biopsy
  shows Hodgkins disease Stage 2. All are true
  except
• 1. Presence of B symptoms is worse for
  prognosis
• 2. B symptoms are fever, increasing size of mass
• 3. Staging depends on whether it is on one or
  both sides of the diaphragm
• 4. Sperm banking should be done
• 5. Second malignancy can occur in patients who
  receive combination chemo and RT

70
Question

• 4 year old boy presents with a 6 day history of
  bilateral, rapidy progressive facial swelling.
  There is no history of associated trauma or upper
  respiratory symptoms. On P/E, there is
  significant swelling below both eyes and of both
  cheeks. The angle of the jaw is maintained. On
  examination of the oral cavity, both the soft and
  hard palate are swollen as are the gingiva. The
  teeth are loose and inverted due to the degree of
  gingival swelling. A CT of the sinuses reveals
  extensive bilateral opacification of both
  maxillary sinuses. LDH was 1,850 U/L.  Which of
  the following is the most likely to cause of this
  patients physical findings? 
• Human herpesvirus 6
• Cytomegalovirus
• Cryptosporidium hominis
• Parvovirus B19
• Epstein-Barr virus

71
Burkitts Lymphoma

• Endemic Burkitts
• African type, head and neck, jaw
• 95 chance of EBV
• Sporadic Burkitts
• Abdomen
• 15-20 chance of EBV
• t (814)
• Immunotherapy Anti-CD 20 monoclonal antibody
  (Rituximab)

72
Question

• 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.

73
Brain Tumors- Important to know

• 20 of all malignancies in children
• Age 3-7 years
• Most often infratentorial
• Sx Persistent vomiting, headache, gait
  imbalance, diplopia, ataxia, vision loss, school
  deterioration, growth deceleration
• Associations with Inherited Genetic disorders
• Neurofibromatosis, Tuberous sclerosis,
  Von-Hippel-Lindau disease, Li-Fraumeni (glioma),
  Turcot syndrome

74
Medulloblastoma

• - most common CNS tumor
• Trt Resection, Craniospinal RT, Chemo
• Prognosis Age, large size, degree of resection,
  dissemination, histology.

75
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.

76
Stage I Wilms- Chance of 4-year survival is
CLOSEST to

1. A. 30
2. B. 45
3. C. 60
4. D. 75
5. E. 95

77
Wilms Tumor- Important

• Presentation No Sx, HT, Hematuria, Malaise
• Histology favorable(FH) vs unfavorable (UH)
• Staging I-local, II-excised, III-residual,
  IV-metastases, V -bilateral
• Treatment Nephrectomy, Chemo-all, St I-II-2
  drugs-18 weeks, St III-IV- 3 drugs RT
• Prognosis
• FH gt 90 at 2 years
• UH lt 60 at 2 years

78
Congenital anomalies associated with Wilms tumor
include all of the following except

1. Polydactyly
2. Aniridia
3. Hemihypertrophy
4. Cryptorchidism
5. Denys-Drash syndrome

79

• 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
• a. Pseudotumor of the orbit
• b. Trichinosis
• c. Retinoblastoma
• d. Rhabdomyosarcoma
• e. Orbital cellulitis

80
Rhabdomyosarcoma

• 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

81
Mass

• 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
  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

82
All statements are true about Neuroblastoma
except

1. Most common extra-cranial solid tumor
2. Prognosis better with N-myc oncogene
   amplification and tumor diploidy (DNA index 1)
3. Most common cancer in the first year of life
4. Frequent in lt4 years, 97 cases by 10 years
5. Most commonly diagnosed as Stage III or IV

83
Case

• 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)-OS
• Xray shows an onion peel appearance- ES
• Xray- radioluscent, sharp, rounded lesion lt 2cm
  with reactive sclerosis- Osteoid Osteoma

84
X ray and MRI
85
Ewings Sarcoma
86
Osteogenic Sarcoma

• MRI, Bone scan, Biopsy, CT Chest for mets.
• Peak incidence- 2nd decade
• Predisposition Hereditary retinoblastomas,
  Li-Fraumeni, Pagets, RT, Alkylating agents
• 60 near the knee (Metaphyses of long bones)
• History of fall, pain common symptom, mass, no
  systemic symptoms.
• Treatment Sperm banking, Neo-adjuvant
  Chemotherapy, limb preserving surgery.

87

• 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

88

89
Retinoblastoma- need to know

• 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.

90
A child with ALL was started on Chemotherapy.
She had a WBC 82,000, Hb 9gm, plt ct 45,000. She
develops tumor lysis syndrome Which depicts
Tumor lysis

1. K high, P high, LDH normal, Na high
2. K high, P normal, LDH high, Na nl
3. K normal, P high, LDH high, Na high
4. K normal, P normal, LDH high, Na normal
5. K high, P high, LDH high, Na normal.

91
Tumor lysis syndrome

• 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.

92
Spinal cord compression

• Presentation back pain worse with movement, neck
  flexion, straight leg raising, valsalva
• Weakness partial/complete paralysis,
  Incontinence
• Local tumor extension or metastasis
• Lymphomas, neuroblastoma, soft tissue sarcomas
• Therapy Urgent treatment to relieve pressure and
  prevent permanent neurologic damage.
• Neurology/Neurosurgery consult
• High dose dexamethasone
• Emergency radiation therapy
• Laminectomy

93
Questions on-Superior Vena Cava Syndrome

• Mass lesion obstructs flow through the SVC
• Symptoms
• - Dyspnea, edema of face, neck, upper extremities
• Periorbital edema, conjunctival edema (itchy
  eyes)
• Dysphagia, resp distress, vocal cord paralysis
• Tracheal compression resp distress, wheezing
• Due to- NHL, Tcell ALL, Lymphoma,
• Secondary cause occluded central venous catheter

94
Chemotherapy-Side effects that you need to know

• Anthracyclines Cardiac toxicity
• Vincristine foot drop, peripheral neuropathy
• Cisplatinum kidney, deafness
• Methotrexate, 6MP Liver toxicity
• Bleomycin Pulmonary fibrosis
• Asparaginase Pancreatitis, Coagulopathy
• Etoposide (VP-16) Secondary AML
• Cyclophosphamaide Hemorrhagic cystitis
• (MESNA as Uroprotector) and Infertility

95
Fever, Neutropenia

• Single most important risk factor ANC
• Organisms Gram negative infection, Staph epi in
  catheter patients
• Medication Broad spectrum 3rd generation
  antibiotics
• Anti-fungal after 4 days
• Examine patient thoroughly

96
16-year-old girl, completed therapy at age 8 for
Hodgkins disease with Involved field RT and
chemo.
She now develops petechiae, purpura,
lymphadenopathy and hepatosplenomegaly.Lab
include plt 12,000,Hb 8.0 gm/dL and WBC
13,000/mm³. She has.

1. AML as a second malignancy
2. Disseminated varicella
3. Drug-induced ITP
4. Late-onset aplastic anemia due to chemotherapy
5. Viral-induced ITP

97
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 lt 5th percentile and she is Tanner
stage I. Most likely to have an abnormal test of

1. Growth hormone
2. Estradiol
3. Follicle stimulating hormone
4. Gonadotropin releasing hormone
5. Thyroid stimulating hormone

98
Need to know- 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 lt 5 years susceptible
• Panhypopituitarism with higher doses
• ovarian failure with RT

99
A 16 year old boy is receiving chemo for
rhabdomyosarcoma
He recd a year of cycles of Vincristine,
Actinimycin-D and Cyclophosphamide. Most likely
endocrinologic late effect of this therapy

1. Growth hormone deficiency
2. Hypothyroidism
3. Impotence
4. Infertility
5. Osteoporosis

100
Chemotherapy effects

• Chemotherapy with alkylating agents
• Females
• less effects than males
• normal puberty
• early menopause
• Males
• irreversible gonadal toxicity
• sterility with azospermia
• Puberty usually not affected (leydig cells)

101
The most common reason for the failure of
hematopoietic stem cell transplantation is

1. Veno-occlusive disease of the liver
2. Disease recurrence
3. Infection
4. Graft vs. host disease
5. Graft rejection

102
GVHD ( Graft vs Host disease) All are true except

1. It is the reaction of the donor lymphocytes
   against the host.
2. Acute GVHD starts within the first 100 days and
   chronic is after 100 days.
3. Affects the skin, liver and GI tract
4. Irradiation of blood products does not help
5. Complete HLA matching prevents GVHD