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Pediatric Hematology- Oncology
Board Review
Richard Drachtman, M.D.
Professor of Pediatrics and Clinical Section Chief –Pediatric Hematology-Oncology
Rutgers Cancer Institute of New Jersey
Rutgers Wood Johnson Medical School
Exam Weights (ie, the percentage of test questions that fall within each content domain)for all three General Pediatrics examinations (initial certification, maintenance ofcertification, and in-training
• Domain 9: Oncology (2%)
• A. Clinical presentation
• B. Malignancies• 1. Hematologic/lymphatic• 2. Central and peripheral nervous systems• 3. Ocular• 4. Renal• 5. Reproductive• 6. Musculoskeletal/dermal
• C. Other Aspects• 1. Complications of cancer treatment• 2. Oncologic emergencies• 3. Pain and palliative care
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Domain 10: Hematology (4%)A. Clinical presentationB. Diseases, disorders, and conditions
1. Quantitative erythrocyte disorders2. Qualitative erythrocyte disorders3. Quantitative leukocyte disorders4. Qualitative leukocyte disorders5. Quantitative platelet disorders6. Qualitative platelet disorders7. Pancytopenia8. Coagulation disorders9. Immune-mediated blood disorders10. Transfusion reaction
ANEMIA (Decreased hemoglobinAnd hematocrit)
MCV
Low High
Iron deficiencyThalassemiaLead poisoningChronic disease
Folate deficiencyVitamin B12 deficiency
Aplastic anemiaPreleukemia (MDS)
Immune hemolytic anemiaLiver disease
Hypothyroidism
Iron deficiencyThalassemia
Lead poisoningChronic disease
Sideroblastic Anemia
Normal
RECTICULOCYTE COUNT
High Low
Anemia can be categorized by MCV (high or low) or
mechanism (are you making too few or destroying too
many or losing red cells
BILIRUBINWHITE CELL ANDPLATELET COUNTNormal
High
Hemorrhage
Hemolytic anemia
COOMBS TEST
Low
NormalIncreased
Bone marrowDepressionMalignancyAplastic anemiaAcquired
Pure red cell aplasiaDiamond Blackfan AnemiaTransient erythroblastopenia Childhood
Infection
Negative Positive
a. CorpuscularExtracorpuscular
Autoimmune hemolytic anemiaPrimarySecondary (e.g., connective tissue disease, drugIsoimmune hemolytic diseaseRh, ABO mismatched transfusion
HemoglobinopathiesHemoglobin electrophoresisEnzyme assaysMembrane defectsAutohemolysisOsmotic fragility
b. Extracorpuscular
IdiopathicSecondaryDrugsInfectionMicroangiopathic
Morphology matters
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Positive Isoimmunization (ABO, Rh, minor blood group, e.g., Kell)
COOMBS TEST
Negative RETICULOCYTE COUNTSubnormal Pure red cell aplasia
Normal or Elevated
MCV
Low Normal or High
Chronic intrauterineblood loss
Alpha Thalassemia syndromes
BLOOD SMEAR
Normal Abnormal
Cont’d
Anemia in the newborn
Normal Blood Smear Abnormal Blood Smear
Rare miscellaneous causesHexokinase deficiencyGalactosemia
Blood lossIatrogenic (samplingFetomaternal/fetoplacental)Twin to twinInternal hemorrhage
Infection, e.gHIVToxoplasmosisCMVRubellaSyphllis
Hereditary spherocytosisHereditary elliptocytosisPyruvate kinase deficiencyG6PD deficiencyDICVitamin E deficiency
Hb MCV RDW FEP Ferritin Ser. Iron TIBC
IDA
Anemia ofChronic Infection
N N N or N or
Beta Thal
N N N or N N
Studies in Microcytic Anemias
THE HISTORY AND PHYSICAL MATTER!
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Hemoglobinopathies:-Quantitative or Qualitative
Sickle Cell Disease:- 1 in 600 African Americans at birth- Autosomal recessive trait- Three major genotypes comprise SCD: HB SS, HB SC, Hb Sthal- Crises include: VOC; Stroke; Priapism; ACS; Splenic Sequestration;Aplastic crisis
- TCD screening for stroke prevention- Importance of Newborn screening
Thalassemias:- Beta and Alpha Thalassemias- Clinical features of Beta thal major- Freq of one or two gene deletions of Alpha gene is 35% in AA- Individuals with both alpha thal trait and SS have less anemia and less stroke than
SS alone but same VOC
Sickle cells - first observationWalter Noel’s blood smear - Dec 31, 1904
Sickle Cell Disease: Pharmacologic Treatment
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Pathophysiology of SCD
In a red blood cell containing mostly Hb S…
…single Hb S molecules in free in solution; allows red cell to be soft, round, and deformable
When oxygenated…
+ O2
- O2
- O2
…Hb S molecules polymerize into long fibers; mishapen, dehydrated and adherent sickle cells.
When deoxygenated
+ O2
Sickle Cell Disease: Pharmacologic Treatment
Pathophysiology of SCD
1. Molecular pathology
2. Biochemical pathology
3. Cellular pathology
4. Vascular pathology
5. Clinical pathology
Sickle Cell Disease: Pharmacologic Treatment
Pathophysiology of SCDConsequences of Hb S polymerization and RBC sickling
• Red cell injury• Hemolysis• RBC dehydration and dense cell formation• Adhesion of RBC to endothelium• Formation of heterocellular aggregates (WBC, ISC)
• Vaso-occlusion
• Local hypoxia, increased Hb S polymer formation
• Propagation of vaso-occlusion in adjacent vasculature
• Deregulations of vasomotor tone by vasodilator
mediators (NO)
Sickle Cell Disease: Pharmacologic Treatment
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Molecular pathology of SCDRegular Hemoglobin Genes and Products
Sickle Cell Disease: Pharmacologic Treatment
F: a2 g2
A2: a2 d2
A: a2 b2
< 2%
< 3%
96%
Hemoglobins by age > 1 yr
Molecular pathology of SCDHemoglobin Genes and Products in SCD-SS
Sickle Cell Disease: Pharmacologic Treatment
Gower 1: z2 e2
Gower 2: a2 e2
Portland: x2 g2
------------------
F: a2 g2
A2: a2 d2
S: a2 bs2
2-20%
3%
80-95%
Hemoglobins in SS by age > 1 yr
Molecular pathology of SCDThe sickle mutation
Sickle Cell Disease: Pharmacologic Treatment
GAG
Glutamic acid
GTG
Valine
The bs Mutation
The same mutation found in all
bs genes around the world
6th Codon of b-Globin Gene
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RBC containing mostly Hb S
- O2
+ O2
+ O2
RBC containing mostly normal Hb
+ O2
- O2
oxygenated deoxygenated
oxygenated deoxygenated
Clinical Pathology of SCD
1. Anemia
2. Vaso-occlusion
3. Acute/Chronic organ damage
Sickle Cell Disease: Pharmacologic Treatment
Clinical Pathology of SCD
1. Anemia• Chronic intravascular hemolytic anemia
• Acute episodes of severe anemia Transient red cell aplasia (parvovirus B19)
Acute splenic sequestration
Acute hemolysis (“hyperhemolysis”)
Sickle Cell Disease: Pharmacologic Treatment
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Clinical Pathology of SCD
2. Vasoocclusive complications
• Microvascular occlusion clinically silent
• Macrovascular occlusion acute ischemic/infarctive damage
pain episodes stroke priapism acute chest syndrome renal papillary necrosis splenic infarction
Sickle Cell Disease: Pharmacologic Treatment
Clinical Pathology of SCD
3. Chronic organ damage
• Splenic dysfunction high risk of bacterial infection
• Progressive dysfunction of: lungs - pulmonary hypertension kidneys - proteinuria, renal failure gallbladder - gallstones eyes - proliferative retinopathy joints - osteonecrosis, arthritis heart - CHF/pulmonary hypertension
Sickle Cell Disease: Pharmacologic Treatment
Pathophysiology of SCDVasoocclusion (1)
A. Prolongation of the RBC microvascular transit time caused by:
Enhanced red cell adhesion to endothelium and heterocellular aggregate formation
Abnormal cation homeostasis with cell dehydration, dense-cell formation, and
irreversibly sickled cell formation
Abnormal vasomotor tone favoring vasoconstriction
Sickle Cell Disease: Pharmacologic Treatment
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Pathophysiology of SCDVasoocclusion (2)
B. Reduction in delay time to HbS polymer formation caused by:
Red-cell deoxygenation
Increase in intracellular HbS concentration
Low concentrations of protective Hb types (eg, HbF, HbA2)
Fall in pH
C. Miscellaneous potential modulators
Free-radical release and reperfusion injury
Coagulation activation with proadhesive thrombin formation
Sickle Cell Disease: Pharmacologic Treatment
1. In vitro gelation studies have shown that Hb F
is effective inhibitor of gelation.
2. Patients with high Hb F levels (> 20%) documented
to have mild clinical course.
3. Patients with S-HPFH produce 25-35% Hb F in every
RBC beyond infancy, and are clinically asymptomatic.
Effect of Hb F on SCD
Hydroxyurea Therapy in Sickle Cell Disease
Hem Onc clinics Kuypers 2014
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Figure 1Pediatric Research (2014) 75, 196–204 doi:10.1038/pr.2013.227
Effect of Hb F on SCD
Hydroxyurea Therapy in Sickle Cell Disease
Beneficial RBC Effects of HU Treatment in SCD-SS
Increase in F-cell numbers and Hb F concentration per F cell
Inhibition of cation depletion and dense-cell formation
Reduction in stress reticulocytes and hemolytic rate
Increased deformability with improved rheology
Inhibition of sickle red cell-endothelium adhesion
Inhibition of sickle erythrocyte adhesion to extracellular
matrix components, including fibronectin,thrombospondin,
and laminin
Hydroxyurea Therapy in Sickle Cell Disease
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• Quantitative reduction in leucocyte count
• Qualitative changes in leucocytes, including reduction in
leucocyte-free-radical production and activation marker
L-selectin
• Reduction in soluble VCAM-1 concentrations (indicative of
decreased endothelial activation)
• In-vivo NO release
Hydroxyurea Therapy in Sickle Cell Disease
Beneficial Non-RBC Effects of HU Treatment in SCD-SS
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Aplastic AnemiaSEVERITY
Moderate aplastic anemia is defined as pancytopenia with the following findings: hypocellular bone marrow aspirate and biopsy and granulocyte count >500/mm, or platelet count>20,000/mm, or red cell transfusion dependency.
Severe aplastic anemia is defined as pancytopenia with the following findings: granulocyte count <500/mm; platelet count, <20,000/mm; reticulocyte count,
<20,000/mm; and bone marrow aspirate and biopsy show aplasia (<25% hematopoietic cells remaining).
Treatment: BMT/ATG-CSA +/- Eltromopag (Promacta)
Aplastic Anemia: Congenital vs. Acquired
Features of Acute and Chronic ITP
Feature Acute Chronic
AgeSex distributionSeasonal predilectionAssociated autoimmuneConditions (e.g., SLEOnsetPlatelet countEosinophilia andLymphocytosis
Antiplatelet antibodiesDurationProgress
Children 2-6 years of ageEqualSpringtime~80%UncommonAcute<20,000/mmCommon
Frequent<12 monthsSpontaneous remission in80% of cases
AdultsFemale: male 3:1NoneUnusualMore commonInsidious40,000-80,000/mmRare
Infrequent12 months +Fluctuating chroniccourse
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Qualitative Inherited Platelet Disorders• Adhesion– Bernard-Soulier• Aggregation– Glanzmann’s• Secretion– E.g. Gray Platelet Syndrome
Glanzmann’s Thrombasthenia• Rare Condition• Inherited absence of GPIIb/IIIa (AR)• Severe Bleeding manifestations• GPIIb/IIIa a key platelet glycoprotein required for aggregation• Absence of aggregation with ADP, Epi, Collagen• Normal ristocetin
Bernard-Soulier• Rare inherited bleeding Disorder: AR• Lack of GPIb which is necessary for the formation of the hemostatic plug by binding to subendothelial von Willebrand factor• Aggregation with ADP, Epi and collagen; absent Ristocetin
. Giant Platelets
PTT
PT Prolonged
Prolonged Normal
TT
Normal Prolonged
Liver diseaseVitamin KDeficiencyCirculatingAnticoagulantCoumadin effect
AfibrinogenemiaDysfibrinogenemiaDisseminatedIntravascularCoagulationHeparin effect
F XIIIdeficiency
Normal PT
Prolonged Normal
F VII,IIDeficiencyFII, XI, VIII,IX
DeficiencyCirculatingAnticoagulantHeparin effectKininogen Deficiencies
Inherited Coagulation Factor Disorders
Associated
WithBleedingEpisodesFactors Deficiency Genetics BT APTT PT
AfibrinogenemiaIIV (parahemophilia)VIIVIII Hemophilia A
von Willebrand's diseaseTypes 1 and 11Type 111
1X (hemophilia B)XX1 (hemophilia c)X11X111
ARARARARXLR
ADARXLRARARADAR
PPPNP
N/PPPPPPN
NNNNN
PPNNNNN
PPPPN
NNNNNNN
++++++++
++++++++++-+
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Von Willebrand Disease (vWD):
- autosomally inherited disorder caused by deficiency (type1) , dysfunction (type 2) or complete absence (type 3) of VWF.- vWF – a large multimeric protein produced in megakaryocytes and endothelial cells as pre pro vWF.-Most common hereditary bleeding disorder - biochemical evidence in 1-2 % of population & bleeding in 0.1%- Type 1 commonest (70-80%) – FVIII dec., vWF:ag dec., R-Co (vWF activity) dec., RIPA induced plt agg N or
Dec.,- Acquired vWF occurs in- Wilms tumor; hypothyroidism; myeloprolif. Dis; angiodysplasia.- Bleeding disorder as opposed to coagulation disorder – in terms of clinical presentation
Lab differences in vWD and Hemophilia
- aPTT Normal or prolonged in vWD Prolonged in Hemophilia- Factor VIII Borderline or decreased Decreased or absent- vWF Ag Decreased or absent Normal or increased- vWF multimers Normal or abnormal Normal
Clinical Indicators of Hypercoagulable State
Family history of thrombosisRecurrent spontaneous thrombosesThrombosis in unusual sitesThrombosis at an early ageResistance to anticoagulant therapyCoumarin necrosis syndromeRecurrent spontaneous abortionsThrombosis during pregnancyMigratory superficial thrombophlebitis
Antiplatelet agentsa. Aspirin 5-10 mg/kg/dayb. Dipyridamole 3-5 mg/kg/day
Coagulation Made Easy
The PTT Pathway The PT Pathway
Rather than thinking about the intrinsic and the extrinsic
pathways, think about the PTT and the PT pathways.
Adapted from Alice Ma MD/UNC
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Coagulation Made Easy
X
The PTT Pathway The PT Pathway
The PT and the PTT pathway
meet at Factor X, because “X”marks the spot.
Coagulation Made Easy
V
X
The PTT Pathway The PT Pathway
Factor V is a cofactor for Factor
X, and you can remember this
because V fits into the notch of
the X.
Coagulation Made Easy
V
X
Prothrombin Thrombin
The PTT Pathway The PT Pathway
Factor Xa converts prothrombin (Factor II) into thrombin, the
most important enzyme on the planet.
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Coagulation Made Easy
V
X
Prothrombin Thrombin
Fibrinogen Fibrin
The PTT Pathway The PT Pathway
Thrombin, among other things,
converts the soluble molecule
fibrinogen into a solid fibrin clot.
The Common Pathway = Small Bills
V + X
II = prothrombin
I = fibrinogen
You can remember the factors in the common pathway by remembering the bills in your
wallet smaller than a $20. Don’t forget the $2 bill!
Coagulation Made Easy: The PT
Prothrombin Thrombin
Fibrinogen Fibrin
7
V
X
The PT PathwayPT has one less letter than PTT, and
PT values are shorter than PTT values,
because the pathway is shorter. It
means that the PT pathway is also
shorter. This means that there’s fewer
steps to remember, and this is lucky, so
the lucky PT pathway uses lucky
Factor 7 to activate Factor X.
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Coagulation Made Easy: The aPTT
Prothrombin Thrombin
Fibrinogen Fibrin
V
X
XIIXI
IXVIII
The PTT pathway has all those
hideous roman numerals. . .
How are we going to remember them?.
.
The PTT Pathway
Coagulation Made Easy: The aPTT
Prothrombin Thrombin
Fibrinogen Fibrin
T
NE
TV
X
E
The PTT Pathway
Well, just remember that the PTT is a
basic TENET of hematology.
TENET stands for. . .
Coagulation Made Easy: The aPTT
Prothrombin Thrombin
Fibrinogen Fibrin
Twelve
Nine
Eight
TenV
X
Eleven
The PTT Pathway
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Coagulation Made Easy: PT and PTT Both Prolonged
V
X
Prothrombin (II)
Fibrinogen
The PTT Pathway The PT Pathway
These factors are in the
common pathway.
Coagulation Made Easy: Only PT Prolonged
7
Deficiency of Factor VII will prolong the PT but not the PTT.
Coagulation Made Easy:
Only PTT Prolonged
Twelve
Nine
Eight
Ten
Eleven
Deficiencies of Factors 12, 11, 9, and
8 will prolong the PTT and not the PT.
Remember that Factor 10 is in the
common pathway, and affects BOTH
the PT and the PTT.
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• Deficiencies of Factor XI, IX,
VIII, VII. X, V, prothrombin, and
fibrinogen are clinically
significant.
• Inhibitors of these factors are
clinically significant for bleeding.
• Deficiency of Factor XII, and the
presence of the lupus
anticoagulant are not.
XII
XI
IX
X
VIII VII
Thrombin
V
Fibrinogen Fibrin
What Matters Clinically
Coagulation Made Easy: The Mixing Study
• Useful to differentiate etiologies of prolonged clotting in a coagulation assay.
• Patient’s plasma is mixed 50/50 with normal plasma. Coagulation assay is repeated.
• If “substantial” correction is noted after mix, suspect clotting factor deficiency, because you replaced deficient factors in the patient plasma with normal factors from the normal plasma.
• If no or not full correction is seen, suspect an inhibitor, because you added the inhibitor (think of this as an anticoagulant) in the patient plasma which inhibits clotting in the normal plasma.
Paroxysmal Nocturnal Hemoglobinuria:
- PIG-A mutation with clonal expansion of hematopoietic cells- Absence of surface CD55/CD59- leads to chronic complement mediated IV hemolysis- Macrocytosis with erythroid dysplasia may evolve in severe AA- Major clinical features:
> PNH with hemoglobinuria and anemia> Bone marrow failure leading to AA – 10%; occ. Leukemia transformation> Venous thrombosis (often cause of mortality)
Rx:> HSCT definitive> Ecluzimab> Cyclosporine / ATG> Support with GCSF/ PRBC Tx/ anticoagulant Rx
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Leucocyte Function Disorders:- About 20% of immune deficiencies- Adhesion deficiencies: LAD 1 - Delayed umbilical cord separation/omphalitis
- Persistent neutrophilia but no pus - Recurrent skin infections; NEC
LAD 2 - Mental Retardation; short stature- WBC 30 to 100K with no pus- Less severe infections
- Chemotaxis: Hyper IgE syndrome(job) - Chronic eczema; delayed teeth shedding; - Recurrent abscesses; Chronic Candida infections- Very high IgE levels; decreased chemotaxis but normal bactericidal fn.
- Degranulation: Chediak Higashi: - oculo--cutaneous albinism; recurrent abscesses; neurol. Features- Death in early childhood- Large granules in in granulated cells and melanosomes; pancytopenia
- Oxidative metabolism: CGD - 65% X linked; absent respiratory burst oxidase; NBT test / Rhodamine- Large nodes; recurrent suppurative infections; granulomas.- Prophylactic antibiotics and rhIFN- Gamma RX
Leukemias:
- Acute Lymphoblastic leukemia: (ALL) 75% - Acute Myeloblastic Leukemia : (AML)- 20%- Acute Undifferentiated Leukemia: <0.5%
Chronic myeloid leukemias: 3% of all childhood leukemias Philadelphia Chr positive ; Juv. Myelomonocytic leukemia- 3-4 cases per 100,000. Peak incidence 2- 5 yrs of age- Account for 25- 30% of all childhood cancers
Hodgkins Lymphoma:- Incidence: 12 per million <20 years; 32 per million 15-19 yrs. - Associated with EBV infection (mixed cellularity type)- Classic hall mark RS cell
Non – Hodgkins Lymphoma: - 6-8% of all malignancies <20yrs age; M:F 2-3:1 Median age 10 yrs- About 70% present with advanced stage disease including extranodal involvement- 25% have Anterior mediastinal mass- Overall survival rates 80-90% EFS
Relative Frequency of Common Childhood Brain Tumors
Location and HematologyFrequency (%)
Supratentorial
Cerebral hemisphereAstrocytomaEpendymoma
GlioblastomaMeningiomaOther
Sella/chiasmCraniopharyngioma
Pituitary adenomaPituitary adenomaOptic nerve gliomaOther
TotalInfratentiorial
CerebellumMedulloblastomaAstrocytomaMeningioma
Brain StemAstrocytomaEpendymomaGlioblastoma
OtherTotal
65544
9322__40
25182
5532___60
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Common Solid Tumors of Childhood
Neuroblastoma: Most common tumor in infancy. 50% are under age 2 ; 75% under 4. - Most common presenting feature- Abd. Mass; with metastases at onset in 75%- Associated Conditions: NF; Hirschsprungs; Heterochromia; Phaeo;Fetal -Hydantoin and alcohol synd.- Increased urine/serum catecholamines . -Opsoclonus-myoclonus
Wilms Tumor: 6% of all childhood cancers. Peak incidence 3- 4 yrs age- 12- 15% associated with congenital anomalies. – aniridia(with 11p13 del); hemihypertrphy, Beckwith –Wiedeman; genito- urinary abn.- S/s: Abd. Mass; hematuria; hypertension; polycythemia; Acq. VWF
Osteosarcoma: Bone tumors account for 2% of all childhood tumors.- Retinoblastoma gene (Rb) Chr 13q14 is implicated on osteosarcoma- Half or more on femur, usually around knee- radioresistant- Amputation/limb spare surg with Chemo
Retinoblastoma: 1/3 cases bilateral and Dx ed during 1st yr of life; 40% hereditary (Auto Dominant)- Most children with Rb have no other abn. - Rb gene assoc, with Soft tissue sarcoma; osteosarc; Adenoca of breast; SCLC- Survivors of Rb have very high risk of sec malig.- Common s/s : Leukocoria; strabismus;Red painful eye.
BMT:Transfusion associated GVHD prevention: Gamma radiated blood; Leucocyte depletion; Selective T cell depletion; UV radiation.
Infections: in first 30 days post Tx: Bacteremia; Invasive fungal; Reactivated herpes simplex- 50- 120 days: Protozoal (PCP; Toxo); Viral – CMV; adeno EBV HHV6; Fungal- After 120 days: Sino- pulmonary infns; Cutaneous Herpes zoster
GVHD: Acute: in first 100 days usually within 30- 40 days; Chronic: after 100 days. Biopsy may be req to differentiate from infection.
Late sequelae of BMT: Growth failure; Chr. GVHD; MEN; second malig; Sterility; cataracts; renal insuff.; Obstruc./ restric. Pulmo disease; cardiomyopathy; Aseptic necrosis of bone; Leukoencephalopathy
Oncologic emergencies: Tumor lysis; Hyperleucocytosis; SIADH; febrile neutropenia; bleeds; typhlitis;
Chronic Effects of Sickle Cell Disease
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Adverse Effect Estimated Risk
Febrile reaction 1/300
Urticaria /other cutaneous reaction 1/50-100
RBC alloimmunization 1/100
Mistransfusion 1/14000-19000
Hemolytic reaction 1/6000
Fatal Hemolysis 1/1000,000
TRALI
HIVHep BHep CAnaphylaxis
1/5000
1/2000,000- 3000,0001/100,0001/1000,0001/20,000 – 50,000
Risks in transfusion per unit Transfused (US)
*Use irradiated cellular products to prevent GVHD especially in preterms and immune compromised
1. Microcytosis in a newborn may indicate all of the following except:
a. A-thalassemia traitb. B-thalassemia traitc. Iron deficiency anemiad. Hemoglobin H disease
2. Persistent reticulocytosis in a newborn suggests the presence of all of the followingexcept
a. Hemolysisb. Hypoglycemiac. Blood lossd. Hypoxiae. G6PD deficiency
3. Fetal to maternal bleeding is suspected in a baby with type A blood to a mother withtype O blood. Which of the following tests may be a strong indicator of this hemorrhage?
a. Positive Coombs test on the babyb. An Acid elution test on the motherc. A rising anti A or anti B titer in the mother following deliveryd. Flow cytometry
4. B-thalassemia trait can be differentiated from iron deficiency because in thalassemia:
a. The RBC count is lower and the MCV is lowerb. The RBC count is higher, the MCV lower and A2 higherc. The RBC count is lower, the MCV lower and A2 higherd. The RBC count is lower, the MCV lower and the A2 normal
5 In thalassemia, iron absorption is:
a. Increasedb. Decreasedc. Unchanged
6 Which of the following newborn screening results is suggestive of sickle cell disease
a. FASb. FSAc. FSCd. FAe. B, c
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Match the site of absorption with the following vitamins and minerals:
a. Duodenumb. Terminal ileumc. Jejunum
7. Iron
8. Vitamin K
9. Vitamin B12
Match the anemia associated with iron deficiency and chronic disorders with the appropriateLaboratory findings:
a. Iron deficiency anemiab. Anemia resulting from chronic disorders (Inflammation, infection) c. Bothd. Neither
10. Reduced serum iron concentration11. Increased erythrocyte protoporphyrin12. Normal or increased total iron binding capacity13. Normal or increased iron stores14. Ferritin less than 25 ng/ml.15. Ringed Sideroblasts in the bone marrow.16. Reduced macrophage iron.
17. In anemia of chronic disorders, serum iron is low because:a. Iron absorption is defectiveb. Erythropoietin response to anemia is inadequate.c. Iron release from macrophages to erythroblasts is defectived. There is increased iron excretion
18. Increased number of the following cells in a bone marrow aspirate of aplastic anemiaIs a poor prognostic indicator:
a. Promyelocytesb. Megakaryocytesc. Lymphocytesd. None of the above
19. Cyclic neutropenia is characterized by all of the following except:
a. Some cases progress to AML if treated with G-CSFb. It is linked to mutation of neutrophil elastase with G-CSFc. Recurring skin infection is commond. G-CSF will improve oscillation of ANCe. GCSF will improve peripheral blood and reduce the signs and symptoms of
Neutropenic nadir
20. Congenital causes of thrombocytopenia include:a. Giant Hemangiomab. Rubellac. Absent radiid. Trisomy syndromee. All of the above
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21. A patient with normal platelet count; normal PTT and prolonged PT has which of the following deficiencies:
a. Factor VII deficiency onlyb. Factors II or VII deficiencyc. Factor V and VII deficiencyd. All of the above
22. All of the factors are produced in the liver except
a. Factor Vb. Antithrombin IIIc. Factor VIIId. Protein Ce. VWF
23. All are true of Aplastic crises except:a. It is caused by B19 parvovirus infection which decreases erythroid activity in the hematopoietic systemb. B19 parvovirus causes Fifth disease and does not cause decrease erythroid activity in the hematopoietic system in
children with sickle cell disesec. Often associated with reticulocytopeniad. Can occur in G6PD deficiency and hereditary spherocytosis
24. All of the following statements are False except:
a. Performing Transcranial Doppler(TCD) is needed for diagnosing stroke in SCDb. A high TCD value suggests high risk of strokec. A low TCD value suggests high risk of stroke in patients with sickle cell traitd. A normal TCD value suggests high risk of stroke
25. On newborn screening for sickle cell disease the following patterns suggest sickle cell trait a. Hb bands F, Sb. Hb F, S, Cc. Hb F, A, Sd. Hb F, A, Barts
26. The nonemetogenic chemotherapeutic agent is:a. Ifosfamideb. Vincristinec. Actinomycin-Dd. Methotrexatee. Cytarabine
27. The clinical presentation of AML in infants less than 2 years of age includes all of the Following characteristics except:
a. Disseminated intravascular coagulationb. Spontaneous remissions occurring frequently in patients with Down Syndromec. t(9;11) with poor, and t(4;11) with favorable prognosisd. Higher leukocyte counts, hepatosplenomegaly and skin lesionse. Petechiae
28. Toxicities of vincristine include all of the following except:a. SIADHb. Insomniac. Constipation and urinary retentiond. Hypotensione. Neurotoxicity, seizure
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29. Testicular relapse in acute lymphoblastic leukemia is most common with all of theFollowing cases of ALL except:
a. White count more than 20,000b. Lymphomatous presentation, T-cell diseasec. CNS involvementd. Significant thrombocytopenia
30. The single greatest determinant of susceptibility to bacterial and fungal infections inA cancer patient is:
a. Colonizing flora and defective skin defenseb. Total white countc. Level of circulating granulocytesd. Circulating immunoglobulin level
31. Infections occurring during the first month after bone marrow transplantationInclude all except:
a. Interstitial pneumonia due mainly to cytomegalovirus before the age ofGanciclovir prophylaxis
b. Pneumocystis jiroveci infectionc. Bacterial sepsisd. Herpes simplex and herpes zostere. Fungal infections
32. Graft versus host disease (GVHD) is caused by and is dependent on all except:a. Humoral antibodiesb. Nature donor T-lymphocytesc. The degree of genetics disparityd. Recognition of non-HLA transplantation antigens by donor T-cellse. Tumor necrosis factor/TNF-1
33. Bone marrow transplant in ALL is strongly recommended in all of the followingsituations except:
a. Persistent minimal residual diseaseb. Early relapsec. Infant ALL with 11q23 rearrangementsd. Bone marrow relapse one years after completion of maintenance therapye. Isolated testicular relapse while receiving chemotherapy
34. Acute tumor lysis may include all of the following except:
a. Hyperuricemia, treated with urate oxidaseb. Hyperkalemiac. Hyponatremia as a result of SIADHd. Hyperphosphatemia with hypocalcemiae. Seizures
35. A history of progressive cranial nerve dysfunction, gait disorder, and cerebellar andPyramidal tract abnormalities is suggestive of:
a. Medulloblastomab. Astrocytomac. Brain stem gliomad. All of the above
36. All of the following are common brain tumors in 2-12 year olds except:
a. Cerebellar astrocytoma (infratentorial)b. Cerebellar astrocytoma (supratentorial)c. Medulloblastoma (infratentiorial)d. Brain stem glioma (infratentiorial)
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37. The most common primary site of osteosarcoma is:a. Distal femurb. Proximal tibiac. Proximal humerusd. Pelvis
38. The primary sites of metastases of osteosarcoma are:a. Lungs and bone marrowb. Lungs and liverc. Lungs and boned. Lungs and brain
39. Clinical presentation of neuroblastoma may include:a. Bone pain and limpingb. Diarrhea, abdominal pain, abdominal mass, anorexia, and weight lossc. Unexplained hypertensiond. Proptosise. Oposclonus-myoclonus syndromef. All of the above
40. The most common presenting symptom of retinoblastoma is:
a. Painful eyes with glaucomab. Strabismusc. Leukocoriad. Blindness
41. Which of the following are included in the etiology of brain tumors?
a. Postnatal radiation exposureb. A late effect of treatment of other cancers, particularly ALLc. A component of Li-Fraumeni syndromed. Increased incidence with neurofibromatosis, tuberous sclerosis and primary
immunodeficiency syndromee. All of the above
42. Neuroblastoma metastasizes to all except:a. Regional and distant Lymph nodesb. Bone marrowc. Liver and Skind. Lungs