Heme/Onc - Week 1 Review - Part 2

Question 1

Four Major Chemotherapy Drug Classes

Answer 1

1) Alkylators
2) ANtimetabolities
3) DNA Repair Inhibitor
4) Anti-Tubulins

Question 2

Cancers with a Chemotherapy as a Possible Cure (3)

Answer 2

1) Hodgkin
2) NHL
3) Testicular

Question 3

Cancers with Chemotherapy Survival Benefit (6)

Answer 3

1) Breast
2) Ovarian
3) Endometrial
4) Cervical
5) Small Cell Lung
6) Colorectal

Question 4

Alkylating Agents - Major Mechanism + Major Toxicities (4)

Answer 4

Mechanism - Trigger bifunctional moieties –> cause double strand breaks

Toxicity - GI Tract + Bone Marrow + Vesicant (infiltration) + Carcinogenic (Increased risk for of AML later in life)

Question 5

CHOP Therapy for NHL and CLL

Answer 5

Cyclophosphamide (Alkylator) + Hydroxydaunorubicin (Doxorubicin) + Nocovorin (Vincristine - Microtubule Inhibitor) + Prednisone

Generics = CDVP

Question 6

Capecitabine - Major Function + Toxicity

Answer 6

Function - Prodrug - Antimetabolite

Causes Foot and Hand Syndrome

Question 7

Leucovorin - Mechanism + Toxicity

Answer 7

Mech - Methotrexate Rescue Drug

No Tox (Tricky)

Question 8

6-MP - Key Toxicity

Answer 8

6-MP Deactivated by Xanthine Oxidase - XO is knocked out by allopurinol - must be careful for co-administration

Question 9

Topoisomerase Inhibitors - Class + Name (3)

Answer 9

Topotecan - Top-1 Inhibitor = Single Strand DNA

Etoposide - Top-2 Inhibitor = Double Strand DNA

Question 10

Vinblastine vs. Vincristine - Major Side Effect

Answer 10

Vinblastine - Vesicant (Infiltration)

Vincristine - Neurotoxicity

Question 11

Lead Time Interval + Bias

Answer 11

Interval - Time from when you would detect disease on screening vs. when the patient would naturally present with s/sx

Bias - Because you see disease early patients who are screened may “live longer” but you may not be slowing the disease, you’re just seeing the course longer

Question 12

Length Bias

Answer 12

Diseases caught on screening are more likely to be slower and less aggressive (rapid/aggressive will show symptoms fast)

Question 13

Prevalence Impact on Screening

Answer 13

High Prevalence increases PPV of a test (more likely to get it right) - Over time screening reduces the prevalence of disease which reduces the effectiveness of the test

Question 14

PSA Testing - Screening Basics

Answer 14

10/100 People Screened with PSA will be Postive

Of Those 10 who are positive 3 will have disease (30%)

Of The 90 who are negative 1 will have the disease (1/90)

Question 15

Imantinib - Key Mechanism + Resistance Site

Answer 15

Mechanism - Blocks BCR-Abl fro t(9:22) in CML

Resistance Pathway - Change in the binding cleft of BCR-Abl

Question 16

Trastuzumab - Mechanism + Key Toxicity

Answer 16

Alternative Name - (Herceptin)

Mechanism - HER2 Signaling

Toxicity - Cardiotoxic (with Doxorubicin)

Question 17

Chronology of Hematopoesis Location During Development - 5 Sites Prior to Birth

Answer 17

1) Yolk Sac
2) Placenta
3-4) Spleen + Fetal Liver
5) Bone Marrow

Question 18

Hematopoeisis Over A Life Time - Locations (After Birth)

Answer 18

High In tibia and femur at both - degenerate and central locations take over
Age 75 - Vertebrae still 75% cellular
Age 20 - Femur only 25% cellular

Question 19

Embryological Origin of Bone Marrow

Answer 19

Mesoderm

Question 20

HSC Niche - 5 Major Factors

Answer 20

1) Osteoblast Notch Pathway
2-4) Endothelial Cells - Kit + CXCL12 and 4
5) Thrombopoetin (Platlet stimulating factor)

Question 21

Major HSC Markers (3)

Answer 21

1) CD34+ - N-Terminus binds ICAM and holds in the Niche
2) Thy1+
3) CD33(-)

Question 22

Other Normal CD Markers (5)

Answer 22

1) CD2-10 - T-Cells
2) CD11-15 - Myeloid + Monocyte Markers
3) CD19-23 - B-Cells
4) CD33 - Immature Myeloid Marker - AML Sign
5) CD56+ - NK Cells

Question 23

HSC Develops into Two Lineages (IL Markers)

Answer 23

1) Common Myeloid Progenitor (CD33+) - IL-3

2) Common Lymphoid Progenitor (TdT+) - IL-7

Question 24

Major Small Lymphocyte IL Molecules - 2 Lineages

Answer 24

T-Lymphocyte (CD2-10) - IL 7 and IL-2

B-Lymphocyte (CD19-23) - IL-4

Question 25

Major IL Molecules for Myeloblast Development (3) + 4 Major Cell Types Produced

Answer 25

1) GM-CSF 2) IL-3 3) IL-5 1) Basophil 2) Eosinophil 3) Neutrophil 4) Monocyte/Macrophage

Question 26

JAK/STAT Pathway - 4 Key Steps

Answer 26

1) Receptor Binding 2) Triggers JAK Activation (Tyrosine Kinase) 3) Phosphorylates STAT 4) STAT Turn on Nuclear Signals

Question 27

Major Interlukins (IL1-8)

Answer 27

Hot T-Bone stEAK IL-1 - Fever + Acute Inflammation IL-2 - T-Cell Activation IL-3 - Bone - Marrow Activation (Common Myeloid Progintor) IL-4 - IgE + IgG Class Switching + Th2 Differentiation + B-Cell Growth (Think Hemoatopoesis) IL-5 - IgA Class Switching + Eosinophilia IL-6 - K - Acute Phase Protein Production (Fever + Protein Synthesis) IL-7 - T-Cell Stimulation IL-8 - Clean-Up on Aisle 8 - Neutrophil Chemotraction

Question 28

EPO Stimulation of RBC Production - 4 Effects

Answer 28

1) Cells Get Small (Microcytic) 2) Cytoplasm Changes - Blue to Pink (More chromatic) 3) Nucleus/Cytoplasm Ratio Falls 4) Nucleus extruded prior to the reticulocyte being kicked out

Question 29

EPO Mechanism of Stimulation

Answer 29

JAK/STAT-5 Pathway

Question 30

Polycythemia Vera - Mechanism (Genetics)

Answer 30

Acquired Jak2 Mutation - Valine to Phenylalaine - Continuous activation of JAX2/STAT5 leads to hypervisciousity

Question 31

Signs of T-Cell Deficiencies (3)

Answer 31

1-2) Fungal Infections - Pneumocystis + Cryptococcus) - Thrush! 3) Herpes

Question 32

Signs of B-Cell Deficiencies (5)

Answer 32

1) Bacterial Pneumonia + Streptococcus 2) Bacterial GI Infection 3) Parasitic Infections (Giardia) 4) Endovirus Infection 5) Encapsulated Bacterial Infection

Question 33

Signs of Granulomatous Phagocyte Deficiencies (4)

Answer 33

1) Recurrent Skin Infection 2) Staph 3) Nocardia (Pneumonia) 4) Aspergillus - Respiratory)

Question 34

Signs of Complement Deficiencies (2)

Answer 34

1) Straight to Sepsis | 2) Neisseria

Question 35

Major T-Cell Deficiencies (4)

Answer 35

1) SCID 2) DiGeorge 3) Ataxia Telangiectasia 4) Wiskott-Aldrich

Question 36

SCID - Genetics + Cause

Answer 36

Genetics - X-Linked Cause - Complete failure of immune T-Cell Function

Question 37

DiGeorge - Cause + Key Facts (5)

Answer 37

Cause - Defects om 3rd + 4th Pharygeal Arch End Organs Key - Facts - CATCH C - Cardiac Abnormality (Tetrology of Fallot) A - Abnormal Facies T - Thymic Aplasia (No T-Cells) C - Cleft Palate H - Hypercalciema due to hypo-parathyroid

Question 38

Ataxia Telangiectasia - Genetics + Cause + Key Facts

Answer 38

Genetics - Variable T-Cell (CD3/4) Deficit Cause - Variable T-Cell (CD3/4) Deficit Key - Facts - 3A's 1) Ataxia 2) Spider Angiomas 3) IgA Deficiency

Question 39

Wiskott Aldrich - Genetics + Key Facts

Answer 39

Genetics - X-Linked (Male) Key - Facts - WATER - Wiscott Aldrich Leads to Thrombocytopenic Purpura + Eczema + Recurrent Infection Low IgG/IgM - High IgE

Question 40

Major B-Cell Deficiencies (3)

Answer 40

1) Selective IgA Deficiency 2) X-Link Agammaglobulinemia - Burtons 3) CVID

Question 41

Selective IgA Deficiency - Cause + Key Facts

Answer 41

Cause - Only IgA Low Key Facts - Transfusion is key - body thinks IgA is foreign (first time builds Abs - second transfusion body attacks)

Question 42

X-Linked Agammaglobulinemia - Genetics + Cause + Key Facts

Answer 42

Genetics - X-Linked Cause - Defect in Burton tyrosine kinase - No B-Cell Maturation Key Facts - High level of infection after 6-months (maternal IgG gone) - Enterovirus common

Question 43

Common Variable Immunodeficiency - Cause + Key Facts

Answer 43

Cause - Low levels of serum Ig with normal B-Cell Levels - don't mature + produce Ig Key Facts - Late Onset (10-30 y/o)

Question 44

Autosomal Dominant Heme/Onc Disorders (7) - With explanations

Answer 44

1) Familial Adenomatous Polyposis - APC Defect predisposes for Colon Cancer 2) Hereditary Spherocytosis - Normocytic Extravascular Anemia - Spheriod erythrocytes from defect in spectrin or ankyrin - Increased MCHC (Red) + RDW (Cell size variety) 3) Li-Fraumeni Syndrome - p53 abnormalities - massive increased risk for cancer 4) Von Hipple Lindaue 5) Retinoblastoma Mutation 6) Job's Syndrome - Overactivation of JAK/STAT3 - Eosinophila + Hyper IgE 7) Diamond Blackfan Anemia - Snub Nose + Short + Pure RBC Aplasia

Question 45

Autosomal Recessive Heme/Onc Disorders (4)

Answer 45

1) Sickle Cell Anemia 2) Thalessemia 3) Leukocyte Adhesion Deficiency Type I 4) Fanconi Anemia

Question 46

X-Linked Recessive Heme/Onc Disorders (8)

Answer 46

1) Burton (X-Linked) Agammaglobulinemia) - B-Cell Disorder 2) Wiskott-Aldrich (T-Cell Disorder) 3) GP6D Deficiency - Low Glutatione = Low tolerance for oxidative stress (fava beans etc.) 4) Hemophilia A 5) Hemophilia B 6) SCID 7) Hyper IgM Syndrome 8) Dyskeratosis Congenita (DKC)

Question 47

Major Granulomatous/Phagocytosis Disease (3)

Answer 47

1) Chronic Granulomatous Disease 2) Chediak-Higashi Syndrome 3) Leukocyte Adhesion Deficiency Type 1

Question 48

Chronic Granulomatous Disease - Pathophysiology + Common Infections (6) + Key Facts (3)

Answer 48

Pathophysiology - Defect in NADPH Oxidase - No respiratory burst and superoxide formation ``` Infections - Catalatse Postive PLACES Pseudomonas Listeria Aspirgilius Candida E. Coli S. Aureus ``` Key Facts - Suceptible to Catalase + Organisms (because they avoid the alternative superoxide pathway) Nitroblue Terazolium Test Postive Major Treatment = PEG-Interferon

Question 49

Chediak-Higashi Syndrome - Pathophysiology + Key Facts

Answer 49

Pathophysiology - Defect in transport to the lysomome Key Facts - Albanism + giant granules in the neutrophils

Question 50

Leukocyte Adhesion Deficiency Type 1 - Genetics + Pathophysiology + Key Facts

Answer 50

Genetics - Autosomal Recessive CD18 Defect Pathophysiology - CD18 Defect Key Facts - Delayed separation of umbilical cord + increased circulating neutrophils

Question 51

Chronic Granulomatous Disease - Key Test + Major Treatment Option

Answer 51

Nitroblue Tetrazolium Test - No NADPH Burst = Negative Test (Doesn't Turn Blue) Positive Test (Functional Burst/No Disease) - NTT Turns Blue Treatment - PEG-Interferon Gamma

Question 52

Think T-Cell vs. Think B-Cell

Answer 52

T-Cell - Infant + Thursh | B-Cell - Otitis Media

Question 53

Myeloperoxidase Defeciency - Key Facts (3)

Answer 53

Loss of Conversion of H2O2 to HOCl Increased Candida Infection Normal Nitro Blue Test

Question 54

Job's Syndrome - Key Fact (4) - Big For Exam

Answer 54

1) Hyper IgE Syndrome (B-Cell) - Eosinophilia 2) Triad - Eosinophilia + Eczema + Recurrent Sinopulmonary Infactions 3) Autosomal Dominant 4) JAK/STAT3 Over-activation