Hematology 2/ Ex. 2/ Intro to leukemia Flashcards

(63 cards)

1
Q

Leukemia definition

A

Progressive, malignant disease of hematopoietic system
Characterized by unregulated proliferation of (usually) 1 cell line

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2
Q

Where do the abnormal cells originate? What happens after?

A

Abnormal cells originate in bone marrow & then spread into peripheral blood

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3
Q

What is the cause of malignancy?

A

Unknown (Exception: radiation, chemo)

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4
Q

How are leukemias grouped?

A

By cell lineage and by the maturity of the affected cells (Acute or chronic)

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5
Q

Acute leukemia is characterized by ______ and is commonly seen in what age group?

A

immature cells; seen commonly in children

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6
Q

What is Leukemic hiatus? What leukemia do we see this in?

A

Gap in normal maturation; No myelos or metas
Seen in acute leukemia

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7
Q

Leukemia is sudden onset, short term, and aggressive, causing lots of

A

infections and hemorrhaging

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8
Q

FAB defines acute leukemia by:
WHO defined acute leukemia by:

A

FAB defines acute leukemia by >30% blasts in bone marrow

WHO defined acute leukemia by >20% blasts in bone marrow (-blastic)

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9
Q

FAB defines acute leukemia by:
WHO defined acute leukemia by:

A

FAB defines acute leukemia by >30% blasts in bone marrow

WHO defined acute leukemia by >20% blasts in bone marrow (-blastic)**

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10
Q

In chronic leukemia, we see what kind of wbcs?

A

ALL stages of maturation, but predominantly mature cells

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11
Q

What kind of onset is chronic leukemia?

A

Insidious onset (Takes a while)

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12
Q

Although chronic leukemia is lengthier and less aggressive, it is harder to recover from than

A

acute leukemia

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13
Q

FAB defines chronic leukemia by:
WHO defined chronic leukemia by:

A

FAB defines chronic leukemia by <30% blasts in bone marrow
WHO defined chronic leukemia by <20% blasts in bone marrow (-cytic)**

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14
Q

What is blast crisis?

A

When chronic turns into acute, meaning end of diagnosis…

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15
Q

Most time, chronic leukemia affects what group?

A

Adults

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16
Q

What is the WBC count in acute and chronic leukemia?

A

Acute: variable (can be very low)
Chronic: high!

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17
Q

What is the plt count in acute and chronic leukemia?

A

Acute: variable (can be very low)
Chronic: normal to increased

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18
Q

Organomegaly in acute is?

A

mild

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19
Q

Organomegaly in chronic leukemia is

A

severe

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20
Q

How did the French-American-British system diagnose leukemia?

A

Cytochemical stains

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21
Q

What are the four methodologies uses for identifying and classifying leukemias?

A

1A. Morphological review of bone marrow
1B. morphological review of peripheral blood smears
2. Cytochemical stains
3. Immuno-phenotyping
4. Cytogenetic and molecular analyses

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22
Q

A morphological bone marrow MUST be done with:

A

a peripheral blood smear (and vise versa)

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23
Q

Bone marrow review is only good for differentiating

A

acute or chronic

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24
Q

Cytochemical stains (NSE, LAP, etc). identifies

A

specific molecules in malignant cells associated w/ specific cell lines (Lipids, enzymes)

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25
Immunophenotyping using flow cytometry for:
specific cell lineage and.or specific maturation stage markers
26
What kind of markers can we find with immunophenotying
surfacem cytoplasmic, nuclear
27
Anauploidy:
increase in risk of relapse
28
Terminal deoxynucleotidyl transferase (TdT) is an enzyme that:
is present only in early lymphoid cells, so you find this increased levels n lymphoblastic leukemias (ALL), but not really in AMLs
29
What are the four major types of leukemia?
1. ALL: Acute lymphoblastic (less specifically, lymphocytic) Leukemia 2. CLL: Chronic lymphocytic leukemia 3. AML: Acute myeloblastic (less specifically, Myelocytic or Myeloid) Leukemia; aka ANILL (Acute Nonlymphocytic Leukemia) 4. CML: Chronic myelocytic/Myelogenous/Myeloid Leukemia
30
Acute myeloid leukemia (AML) subclassifications
Myelocytic/Myelogenous Promyelocytic Monocytic Myelomonocytic (AMML) Erythrocytic (AEL) Megakaryocytic (AMegL)
31
Acute lymphoid (ALL) subclassification
T-Lymphocytic B-Lymphocytic Null Cell (?)
32
chronic myeloid leukemia subclassifications:
Myelocytic/ Myelogenous (CML) Myelomonocytic (CMML)
33
Chronic lymphocytic leukemia subclassifications:
Lymphocytic (CLL) Plasmacytic Hairy Cell (HCL) Prolymphocytic (PLL)
34
Few exceptions to 'unknown' cause:
Genetics Leukemoge Viral infections Radiation
35
What are leukemogens?
Chemicals causing bone marrow depression and aplasia predispose to leukemia later on (Ex. benzene, chloramphenicol, sulfa drugs, insecticides, antineoplastics)
36
How do viral infections cause leukemias?
Some retroviruses transform N. cells by inserting their own oncogenes into the host cell's genome, causing them to become malignant. [EBV linked to Burkitt non-hodgkin lymphoma]
37
Proto-oncogenes are normal genes which become altered by mutation to become
oncogenes (genes that cause cancer mutations)
38
2 examples of mutated versions of proto-oncogene
CML t(9;22) and Burkitt Lymphoma t(8;14) CML: ABL proto-oncogene on chromosome 9 is activated when fused with the BCR component of chromosome 22 Burkitt lymphoma: MYCproto-oncogene on chromosome 8 is activated when fused with Ig on chromosome 14
39
Aneuploid:
chromosome number that is abnormal
40
Tumor suppressor genes code for
proteins which resist malignancy
41
Lab evaluation steps
1. Preliminary workout up of peripheral blood: CBS w/ plt and diff., RBCs smear, Plt and WBC count, and differential 2. Secondary stage workup: bone marrow aspirate and biopsy analysis, cytochemistry (special stains), immuno-phenotying (ABs and fluorescent stains), cytogenic studies (PCR and FISH)
42
Minimal residual disease (MRD) is detected via cytogenic studies (PCR and FISH) to detect:
lowest level of disease detectable in patients who are in continous clinical remisssion
43
What is the minimum % of blasts in bone marrow required for acute diagnosis in FAB system?
30%
44
What is the minimum % of blasts in bone marrow required for acute diagnosis in WHO system?
20%
45
Methods are sensitivity to
levels of tumor burden (amount of cancel cell present in pts body)
46
Treatment must start with a good and accurate: What are the two goals?
Must start with a good/accurate diagnosis Two goals: (Depends on prognosis/treatments) 1. Eradicate leukemic cell mass 2. Provide supportive care for symptoms
47
Four factors playing roles in prognosis & treatment modalities are the patients:
Pretreatment health status Age Concurrent infection Abnormal cytogenetics
48
The younger the patient & the less symptomatic, the greater the
response to therapy likely will be
49
Categories of leukemia therapy:
1. Chemotherapy 2. Radiation therapy 3. Supportive therapy 4. Targeted therapy 5. Stem cell transplantation
50
Describe the first line of leukemia therapy and its three stages of therapeutic strategy
Typically given through IV w/ antibiotics for diffuse malignancies Three stages of therapeutic strategy: 1. Induction – of complete remission (Normal bone marrow cellularity = < 5% blasts!) 2. Consolidation – low dose chemo. To prevent recurrence 3. Maintenance – of remission
51
Describe the 2nd line of leukemia therapy
Radiation; Produces unstable ions that damage cancer cells’ DNA Used for localized malignancies
52
Describe the 3rd line of leukemia therapy
-Used to support cancer patients -Allow for more efficient and effective delivery of chemotherapy regimens by preventing delays or dose reductions due to low blood counts -Examples are colony stimulating factors & EPO (to help spare the remaining cells)
53
Describe the 4th line of leukemia therapy
Targeted therapy: Monoclonal antibodies which bind directly to affect cell, activates complement, and cell lysis
54
Describe the best, but last line of leukemia therapy
Bone marrow or stem cell transplant!! -Patient should be in good clinical condition & in 1st clinical remission for best results -The effort to isolate stem cells from non-embryonic sources is making tremendous strides -Classic approach typically requires intensive chemotherapy, then total body irradiation
55
What are the three types of donors for BMT, or SCT?
1. Syngeneic: identical twin donor (most rare most desired) 2. Allogenic: donor genetically diff. from recipeient 3. Autologous: patients own marrow or peripheral blood stem cells
56
Common clinical symptoms of all leukemias (to a greater or lesser degree), due to (5)
Due to bone marrow overcrowding: Myelopthisic anemia Due to anemia: Malaise, fatigue, pallor (dyspnea if severe) Due to thrombocytopenia: petichiae, epistaxis, hemorrhage Due to extreme anemia: extramedullary hematopoiesis, causing hepatosplenomegaly (Can further exacerbate anemia!!) Due to neutropenia: increased overwhelming infections **Primary cause of death in leukemia*
57
Leukemoid reaction
a. Transient, reactive leukocytosis due to infection b. Temporary resemblance of peripheral blood picture to “leukemic picture” c. Severe left shift & very rare nRBCs (WBCT > 50,000/uL)
58
Leukoerythroblastic reaction (aka. Leukoerythroblastic anemia, or Leukoerythroblastosis)
a. Presence of both nRBCs & left shift in peripheral blood b. Caused by bone marrow damage from a malignant, “space-occupying lesion”, with consequent extensive extramedullary hematopoiesis c. May be mild or severe, & occurs in CML & in lymphomas
59
What is the LAP stain?
Leukocyte Alkaline Phosphatase (LAP): An enzyme found in the secondary granules of neutrophils The substrate naphthol AS-B1 phosphate is hydrolyzed by the enzyme at an alkaline pH, and dyed to produce a colored precipitate **Two slides are obtained per patient, and activity as graded from o to 4+ (performed by two techs, and must agree within 10%)
60
How can we differentiate leukemoid reaction vs CML?
LAP stain!!!
61
LAP is ____ in early leukemia
decreased; because leukemic neutrophils are too abnormal to expresses the LAP that normal mature bands & segs would
62
LAP is ___ in leukemoid reaction due to left shift
increased; because there are tons of band & segs full of secondary granules containing LAP, just waiting to attack the infectious invaders – it only looks like leukemia because of the high WBC count. Also, you see only very rare nRBCS!
63
Normal LAP score?
15-170