Week 24 Hematologic Malignancies Flashcards
1
Q
What is acute leukemia?
A
Neoplasm arising in bone marrow.
Usually sends malignant cells to the blood.
Acute Myeloid leukemia (AML)
Acute lymphoid leukemia (ALL)
2
Q
Leukemia vs Lymphoma
A
Leukemia predominantly in the blood and marrow.
Lymphoma predominantly in the lymph nodes.
3
Q
Indications for RBC transfusions
A
Symptomatic anemia.
Improved O2 carrying capacity.
Acute blood loss.
Suppression of abnormal erythropoiesis.
4
Q
Hemoglobin levels and RBC transfusions
A
> 90 g/L: not needed.
70-90 g/L: only if s&s of anemia present.
<70 g/L: Likely appropriate.
<50g/L: recommended.
5
Q
What type of antigens are expressed on RBCs?
A
Carbohydrates.
O, A, B, AB.
6
Q
What type of antibodies react to ABO antigens?
A
IgM.
React immediately, fix complement.
7
Q
Which ABO group is the universal plasma donor?
A
AB
8
Q
Which ABO group is the universal RBC donor?
A
O
9
Q
What is a group and screen?
A
Group: determines ABO group and RhD status.
Screen: checks for allo antibodies.
Used to determine which blood components can be transfused to the patient.
10
Q
What is the consequence of incompatibility of ABO and plasma?
A
IgM abs will activate complement, causing hemolysis.
Critically important in transfusion safety, maternal-fetal health, and organ transplantation.
11
Q
What condition can occur d/t ABO incompatibility?
A
Acute hemolytic transfusion reaction.
12
Q
Why is it important to screen plasma?
A
Patients may acquire alloantibodies.
Typically IgG antibodies.
13
Q
Discuss ordering a group and screen
A
Required for everyone who gets a routine transfusion.
Done if patient might need a transfusion.
Result is good for 96 hours.
14
Q
Discuss crossmatch
A
Final compatibility test before transfusion.
Mixes patient plasma with donor.
Can be electronic, immediate spin, indirect antiglobulin.
15
Q
What components of blood are available for transfusion?
A
RBC
Plasma
Platelets
16
Q
Discuss minimal effective dose for transfusions
A
Single unit transfusion.
Minimize risk and donor exposure.
Reassess symptoms and HGb after 1 unit.
17
Q
What are the parts of an order for a transfusion?
A
Component.
Volume.
Route.
Rate.
Other (patient on other drugs, age, CV status, reason…)
18
Q
What is the approach to a suspected transfusion reaction?
A
STOP THE TRANSFUSION.
Assess the patient.
Follow up tests.
19
Q
What are the 2 types of transfusion reactions?
A
Acute: <24 hrs.
Delayed: >24 hrs.
20
Q
Signs and symptoms of acute transfusion reactions
A
Minor reactions and life threatening symptoms overlap.
FEVER: >1C increase and >38C up to 4 hours post transfusion.
HYPOTENSION: Drop in systolic of >30 within 1 hour and systolic <80.
HYPOXIA: SpO2<90%
21
Q
What is the ddx for hives or itching post transfusion?
A
Minor allergic reaction.
Anaphylaxis.
22
Q
What is the ddx for fever or chills post transfusion?
A
Primary: Febrile non-hemolytic transfusion reaction.
23
Q
What is the ddx for SOB or hypoxia post transfusion?
A
Primary: Transfusion associated circulatory overload.
Most common cause of death related to transfusion.
24
Q
What is your role as MD in a transfusion reaction?
A
Assess and examine patient.
Form differential.
Order treatments and tests.
Call Transfusion MD to interpret reaction from tests done.
25
Are hematologic malignancies involving platelets myeloid or lymphoid?
Myeloid.
26
Acute myleoid malignancies
Acute myeloid leukemia AML
Subtype APL
(Myelodysplastic syndrome - can progress to AML)
27
Mature myeloid malignancies
Myeloproliferative Syndrome (MPS):
Chronic myeloid leukemia,
Polycythemia Vera,
Essential Thrombocytopenia,
Myelofibrosis.
28
Acute lymphoid malignancies
ALL (t or b cell).
29
Mature lymphoid malignancies
B-cell small lymphocytic lymphoma (SLL).
B-cell chronic lymphocytic lymphoma (CLL).
Diffuse large B-cell neoplasm.
Follicular lymphoma.
Multiple myeloma.
30
History for bleeding disorders
When did bleeding start?
How long does it last?
How much blood was lost?
Trauma?
Easy/spontaneous bruising?
Size of bruises?
Any symptoms of anemia?
Med conditions.
Changes in health.
Past bleeding issues.
MENSTRUAL HX.
Dental/surgical challenges?
Meds?
OTC/supplements?
Fam hx.
31
Physical exam for bleeding disorders
Look for evidence of recent bleeding.
Mouth: mucosal bleeding.
Skin: hematoma/ecchymosis/petechiae.
MSK: hemarthrosis.
Signs of conditions that lead to secondary bleeding disorders: liver, kidney, lymph.
32
Labs for bleeding disorders
CBC
Blood film
PT/INR
PTT
consider liver enzymes, creatinine
33
Mucocutaneous bleeding with normal platelet count indicates what type of platelet abnormality?
Qualitative.
34
What are the types of factor abnormalities that can contribute to bleeding disorders?
Deficiency.
Inhibitor.
35
What lab test helps differentiate between factor deficiency vs inhibitor?
Mixing test.
36
Discuss DIC
Important cause of coagulopathy.
Indiscriminate activation of clotting factors, leading to consumption of clotting factors and platelets.
Causes are numerous (underlying illness).
Presents as SUPER SICK.
PTT/INR both prolonged with similar increase.
Platelets low.
Some schistocytes.
Fibrinogen low.
37
How does warfarin lead to prolonged INR/PT?
Warfarin inhibits Vit K reductase.
Vit K needed for 1972.
38
What are the broad reasons for abnormality of coagulation factors?
Reduced production.
Increased consumption.
Inhibition.
39
Lupus anticoagulant
NOT a coagulant.
Can be triggered by acute viral infections, drugs, or AI conditions.
Causes prolonged PTT in lab only.
Antiphospholipid autoantibodies that bind to phopholipid and proteins involved in cascade.
Stimulates cascade, risk of pathologic thrombosis.
PROCOAGULANT IN PATIENT.
40
What are the 3 main questions used to classify hematologic malignancies?
1. What is the main finding on CBC?
~Up/down/normal
2. Are the malignant cells myeloid or lymphoid?
3. What are the malignant cells doing?
~Stuck/maturing/not good enough
41
What are some reasons for increased blood cell counts?
Increased proliferation.
Increased division.
Avoiding cell death.
42
What are some reasons for low blood cell counts?
Reduced production because of a bad neighbour.
Ineffective/dysplastic cell line.
43
Discuss flow cytrometry
Immunophenotyping.
Monoclonal abs used to characterize surface proteins.
Helps define cell type, age, and whether they are reactive (infection) or clonal (malignancy).
44
What tests are performed to help with hematologic malignancies?
Flow cytrometry.
FISH.
Karyotyping.
Bone marrow aspirate and biopsy.
Lymph node biopsy.
PCR.
SPEP.
45
Malignancy predominantly in the blood and marrow
Leukemia
46
Malignancy predominantly in the lymph nodes
Lymphoma
47
What markers are targeted in B-cells for autoantibody therapy?
CD20 - gets the teenagers.
48
What is the key finding on CBC for CLL?
Very high lymphocyte counts.
Arises in bone marrow and then sends malignant cells into the blood.
49
How is CLL diagnosed?
CBC
Blood film.
Flow cytrometry.
Bone marrow.
Genetic tests.
50
How is CLL treated?
Chemotherapy.
Targeted therapies.
51
What are the key points for MPNs?
Aries in bone marrow and send malignant cells into the blood.
Malignant cells are maturing, not all blasts.
CBC counts usually increase.
52
What are the 4 types of MPNs
Chronic myeloid leukemia (CLL).
Polycythemia Vera (PV)
Essential thrombosis (ET)
Myelofibrosis (MF).
53
What testing is used to diagnose MPNs?
CBC.
Blood film.
Bone marrow.
Molecular testing for individual mutations that are unique to each subtype.
54
What is the treatment for MPNs?
Chemotherapy.
Drugs targeting specific driver mutations.
55
Key findings for MDS
Present with symptoms of low blood counts.
Low counts on CBC.
Abnormal cells may die before leaving marrow.
Blasts can transform to AML.
56
How is MDS diagnoses?
CBC.
Blood film.
Bone marrow.
Genetic tests.
57
Treatment for MDS
Difficult to treat.
Supportive care.
Chemotherapy.
Bone marrow transplant.
58
Discuss supportive treatments for ALL
Blood products.
Lysis suppression.
Fever suppression.
59
Discuss specific treatments for ALL
Chemo - over a course of 2 years.
Radiation.
Steroids to decrease risk of spread to CNS.
Rituzimab.
60
What are the 5 phases of therapy for ALL
Induction.
Consolidation.
Interim maintenance.
Delayed intensification.
Maintenance.
61
What are the 2 major classifications of lymphadenopathy?
Benign.
Malignant.
62
What is needed to diagnose lymphoma?
Excisional lymph node biopsy.
63
What type of cells present in lymph node biopsy as "owl's eye" morphology?
Reed-Sternberg.
64
What are the cells seen in Hodgkins lymphoma?
Hodgkin and Reed-Sternberg (HRS).
These are the only malignant cells so flow cytrometry will not be helpful.
65
Staging of Hodgkin Lymphoma
I - one node area.
II - 2 or more node areas on same side of diaphragm.
III - 2 or more node areas of both sides of diaphragm.
IV - node areas + diffuse or disseminated disease.
66
What is used after the stage to indicate unexplained fever, drenching night sweats, or unexplained wt loss?
B for B symptoms.
A is used if no B symptoms present.
67
How is staging of Hodgkin Lymphoma establised?
Physical exam.
CT scans.
PET scans.
68
Treatment and prognosis of Hodgkin Lymphoma?
Multi-agent chemotherapy.
Possible radiation.
85-80% cure rate for advanced stage.
90-95% cure rate for limited stage.
69
What is a characteristic appearance of CLL lymphocytes on blood film?
Clumped chromatin pattern in nucleus.
"Soccer ball" appearance.
Smudge cells which may also be present in benign lymphocytosis.
70
How can CLL be dianosed?
One of the few that can be diagnosed based on blood film and flow cytrometry alone.
71
Define indolent lymphomas
Generally slow growing, but not curable.
72
Define aggressive lymphomas
Generally fast growing, but curable.
73
What are the 3 main causes for splenomegaly?
Congestive
Infiltrative
Reactive (Work hypertrophy)
74
Causes of congestive splenomegaly
Organ failure: heart/liver.
Obstruction: IVC, thrombosis of portal, hepatic, or splenic veins.
75
Causes of Infiltrative splenomegaly
Metabolic: storage diseases.
Benign: Hamartoma, cyst.
Malignant: Leukemia, lymphoma.
76
Causes of Reactive spelomegaly
Immune hyperplasia: chronic infections, chronic inflammation.
Red cell sequestration: hemolytic anemia, extramedullary hematopoiesis, thalassemia, MPNs
77
Extramedullary hematopoiesis
Hematopoietic stem cells from marrow displaced to spleen d/t some sort of infiltrate in bone marrow.
Spleen tries to compensate by becoming site of hematopoiesis.
Also can occur in beta thalassemia major.
78
What are the 4 major criteria for diagnosis of Essential Thrombocytopenia?
Platelets >450
Marrow biopsy shows increased and abnormal megakaryocytes.
Criteria for other MPNs not met.
JAK2, CALR, or MPL mutation.
79
What is the appearance of marrow in ET?
Increased megakaryocytes.
Abnormal megakaryocytes.
Nomocellular marrow with normal fat spaces.
80
Erythromelalgia
Burning and redness of digits related to microvascular platelet thrombi.
Responds well to aspirin therapy.
81
Rouleaux
Stack of coin appearance of RBCs on blood film.
D/t increased serum proteins that enhance membrane interaction between RBCs.
Increased fibrinogen, immunoglobulins, or abnormal proteins.
82
Plasma cell myeloma
(multiple myeloma)
CRABi
hyperCalcemia
Renal impairment
Anemia
Bone pain
infections
83
Diagnostic criteria for myeloma
>=10% clonal plasma cells in bone marrow
AND
1 CRAB feature.
84
Imaging for plasma cell myleoma
CT skeletal survey.
Whole body MRI.
Plain x-ray skeletal survey (if no CT/MRI available).
These give an idea of the extent, fractures, spinal cord compression.
85
What do marrow aspirate films show you?
Assess the number of all cell lines.
Morphology.
Abnormal infiltrate.
86
List common myeloma emergencies
Hypercalcemia
Acute kidney injury
Severe anemia
Severe pain
87
Discuss treatment and prognosis of myeloma
Treatment is complex, usually:
Chemotherapy
Immunotherapies
Stem cell transplantation.
Prognosis:
Incurable
Life expectancy 5-10 years.
88
What does SPEP detect?
Monoclonal immunoglobulins secreted by clonal cells.
SPEP detects the intact immunoglobulin with both heavy and light chains.
89
What does UPEP detect?
Monoclonal free light chains.
90
What is an abnormal SPEP result?
Narrow and tall peak for gamma fraction.
91
What is the critical test for CML
Philedelphia chromosome t(9;22).
Molecular analysis for the fusion of BCR::ABL.
92
Lymphoid neoplasm
Lymphoproliferation d/t uncontrolled accumulation of lymphocytes
93
What is a shift left in immune system?
Immunodeficiency
94
What is a shift right in immune system?
Lymphoproliferative disease
95
What occurs in Burkitt lymphoma?
Translocation of (8;14) resulting in IGH-MYC fusion gene.
Constitutive expression of IGH causes overexpression of MYC leading to excessive proliferation.
96
Examples of oncogenic viruses
EBV
HIV
HCV
HHV-8
97
Discuss antigenic overstimulation as a mechanism for genetic transformation.
Too much antigen stimulation can lead to genetic alteration, leading to cells that are no longer recognized by T-suppressor cells.
98
Common causes of antigen overstimulation
Micro-organisms: H-pylori, C. psittaci, B. burgdoferi.
AI disease: RA, SLE, celiac, IBD
99
Discuss immunosuppression as a mechanism for genetic transformation.
Immunosuppression d/t meds, HIV, senile immunosuppression.
Escape T-suppressor cells.
100
Prognosis for SLL/CLL
Incurable.
Indolent disease.
Patients can liver for years with the disease.
101
Discuss follicular lymphoma
Middle age- elderly W>M.
Predominantly involves nodes.
Most patients present with stage III/IV.
t(14;18) decreased tumour suppressor gene.
102
Discuss Large B-Cell Lymphoma
Most common lymphoma.
Mostly elderly M>W.
Anywhere in the body.
Rapidly enlarging mass.
50% of patients present stage III/IV
103
Which condition has presence of M-protein
Plasma cell myeloma
104
Functions of the spleen
Filter blood.
Immunity.
Recycles old cells.
105
What is the risk of no spleen
Susceptible to encapsulated organisms.
106
How does lymphoma affect the spleen?
Malignant transformation of white pulp.
107
What is meant by left shift in CBC?
Presence of immature WBCs.
108
Common clinical presentation of MPN.
Increased blood counts.
Fatigue.
Weight loss.
Night sweats.
Abdominal fullness (d/t splenomegaly).
Anexoria.
109
What causes CML?
Malignant clonal disorder of pluripotent stem cell.
Increased granulocytic cells.
Philadelphia chromosome.
t(9;22)
BCR::ABL gene.
110
Phases of CML
Chronic phase: 5-6 years stabilization.
Accelerated phase: 6-9 months.
Blast crisis: 3-6 months survival.
111
CMT treatment
TKi's specific to BCR::ABL.
ImaTINIB, **all the TINIBs
112
Polycythemia
Elevated hematocrit
113
Causes of polycythemia
Spurious
True polycythemia (consistent presentation):
Primary
Secondary (d/t O2 depletion).
114
Spurious polycythemia
Hematocrit increased d/t low plasma volume (dehydration).
115
Secondary polycythemia
Marrow response to hypoxia or high EPO levels.
116
Polycythemia Vera
Increased RBO production WITHOUT elevated EPO.
Mutated JAK2 binds to EPO receptor.
Will have decreased EPO levels, but RBC production continues.
117
Clinical presentation and complications of PV
Facial plethora, erythromelalgia.
Thrombosis.
Platelet dysfunction - bleeding.
Elevated histamine - pruritis/PUD.
Increased uric acid - gout.
Progression to myelofibrosis and AML.
118
Management of PV
Hydroxyurea (over 60 years or thrombotic hx).
Phlebotomy.
Aspirina.
Management of CV risk factors.
119
Clinical presentation and complications of ET
Clotting or bleeding (dysfunctional platelets).
Thrombosis.
Bleeding complications.
120
Treatment for ET
Aspirin for all patients.
Hydroxyurea over 60 or hx of thrombosis.
RuxoTINIB (JAK2i).
121
What mutations or genetic changes can be present in AML
t(15;17) PML::RARA
122
What unique feature of AML is present in blood film?
Auer rods
123
Bone marrow presentation in AML
Lots of blasts.
Little or no normal marrow.
Fat spaces absent.
124
Discuss emergency presentation of AML
Hyperviscosity
Tumour lysis
DIC
Febrile neutropenia
125
Treatment and prognosis for AML
Younger fit patients: intensive chemotherapy +/- stem cell transplant. Aim is for cure.
Older unfit patients: palliative treatment.
Supportive for all:
RBC & plt transfusions.
Treat infections
Lower blast count (hydroxyurea).
126
MDS clinical presentation
Older age.
Fatigue, bleeding, infections.
127
Treatment for MDS
Supportive care:
RBC/plt transfusions.
Treat infections.
Lower blast counts (hydroxyurea).
Chemotherapy
Stem cell transplant
Prognosis depends on age and risk 1-9 years.
128
HLA matching
Determined by DNA, common between ethnic groups.
Best outcomes when donor and recipient are well matched.
ABO is not a limit for stem cells but HLA is.
129
Describe the SPIKES protocol
S: Setting
P: Perception
I: Invitation
K: Knowledge
E: Empathy
S: Summarize/strategy
130
What are the most important features in the delivery of bad news?
Attitude of the person giving the news.
Clarity of the message.
Privacy.
Ability to answer questions.
131
Physician fears when delivering bad news
Being blamed.
Fear of triggering a reaction.
Fear of expressing emotion.
Fear of not knowing all the answers.
132
What are some pitfalls to be cautious of when delivering bad news?
Creating false expectations.
Giving erroneous information.
Lack of humility.
133
List 4 types of shock
Hypovolemic
Distributed
Cardiogenic
Obstructive
134
What leads to hypovolemic shock?
Hemorrhage.
Burns.
Other forms of fluid loss.
135
What systems are involved in the multi-system response to shock?
Cardiovascular.
Pulmonary.
Renal.
Hematologic.
Hormonal.
136
How does the SNS become a driving force of the physiologic response to hemorrhage?
Ctx of vessels in extremities.
Increased heart rate and contractility.
137
CV system response in hypovolemic shock
Increased heart rate.
Increased contractility.
Ctx peripheral blood vessels.
Redistributes blood to brain, heart, and kidneys.
138
What causes the CV responses in shock?
Increased release of epinephrine.
Decreased baseline vagal tone d/t to barorecptors in carotid arch, aortic arch, left atrium, and pulmonary vessels.
139
Respiratory response in shock
Decreased blood flow to brain leads to acidic environment (CO2 buildup).
Low pH drives increased respiration via chemoreceptors in medulla.
Increased respiratory centre activation and sympathetic drive.
140
Renal system response in shock
Increase renin secretion leading to increased angiotensin II:
Vasoconstriction of arteries and veins.
Stimulation of aldosterone.
Aldosterone leads to Na+ reabsorption and H2O conservation.
141
Neuroendocrine response in shock
Increased ADH d/t decrease in BP and [Na+].
142
Hematologic response in shock
Activation of coagulation cascade.
Contraction of bleeding vessels.
Platelet activation.
Collage exposure of damaged vessel stimulates fibrin deposition and clot stabilization.
24 hours for complete clot fibrination and mature clot formation.
143
How is homeostasis restored via the systemic response in shock.
Drop in BP moved fluid from interstitium into plasma.
This dilutes the blood causing decreased hematocrit.
Conservation of H2O from renal system/hormones.
EPO stimulation from low O2.
Activation of thirst centre via baroreceptors, blood volume receptors, osmoreceptors, angII
144
Anticipatory guidance
proactive counselling that addresses the potential medical issues that may arise d/t the underlying diagnosis.
145
Symptomatic therapies
Interventions to alleviate the symptoms of the disease without directly targeting the underlying root cause.
146
Disease-modifying therapies
Interventions that delay or slow the progression of a disease by targeting the underlying root cause.
147
Curative therapies
Interventions that eradicate the causative genetic or molecular aberration thereby eliminating the root cause and preventing symptoms from developing.
148
Inborn errors in metabolism
Group of genetic disorders characterized by disruption of metabolic pathways due to deficient enzymes, cofactors, or transporters.
149
How can pathways be manipulated in inborn errors in metabolism?
Dietary restriction and supplementation.
Toxin removal.
Substrate reduction therapy.
150
Enzyme replacement therapy
Directly replaces deficient enzyme in order to reduce the accumulated substrate.
151
Gene therapy
A set of strategies that modiry the expression of an individual's genes or repair abnormal genes.
Involves the administration of a specific nucleic acid via viral or non-viral vector.
152
RNA based vectors
Target RNA.
Do not alter DNA.
Often need repeat dosing.
153
DNA based vectors
Target DNA altering the production of RNA and proteins.
Must be delivered to nucleus.
Greater chance of permanent alteration (single dosing).
154
Types of RNA based therapies
RNA interference: reduce toxic protein expression by degrading specific mRNA.
Exon skipping: Small stranded sequences of single stranded DNA interfere with RNA typical functions. Goal is to exclude and exon from pre-mRNA, changes protein to have no function.
155
Types of DNA based therapies
Replace a disease causing gene with a healthy copy of the gene.
Inactivate a disease causing gene.
Introduce a new or modified gene to help treat a disease.
156
What are the requirements for gene therapy?
Known molecular defect.
Functional copy of the gene.
Appropriate vector.
Knowledge of the pathophysiology mechanism.
Risk:benefit ratio.
Regulatory components for the transgene.
Appropriate target cell.
Strong evidence for efficacy and safety.
Regulatory approval.
157
CAR T-cell therapies
Receptor proteins that have been engineered to give T-cells a new target antigen.
T-cells are harvested, adjusted to be specific to the tumour.
158
