Hematology 2/ Ex. 2/ Intro to leukemia Flashcards

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
Q

Immunophenotyping using flow cytometry for:

A

specific cell lineage and.or specific maturation stage markers

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26
Q

What kind of markers can we find with immunophenotying

A

surfacem cytoplasmic, nuclear

27
Q

Anauploidy:

A

increase in risk of relapse

28
Q

Terminal deoxynucleotidyl transferase (TdT) is an enzyme that:

A

is present only in early lymphoid cells, so you find this increased levels n lymphoblastic leukemias (ALL), but not really in AMLs

29
Q

What are the four major types of leukemia?

A
  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
Q

Acute myeloid leukemia (AML) subclassifications

A

Myelocytic/Myelogenous
Promyelocytic
Monocytic
Myelomonocytic (AMML)
Erythrocytic (AEL)
Megakaryocytic (AMegL)

31
Q

Acute lymphoid (ALL) subclassification

A

T-Lymphocytic
B-Lymphocytic
Null Cell (?)

32
Q

chronic myeloid leukemia subclassifications:

A

Myelocytic/
Myelogenous (CML)
Myelomonocytic (CMML)

33
Q

Chronic lymphocytic leukemia subclassifications:

A

Lymphocytic (CLL)
Plasmacytic
Hairy Cell (HCL)
Prolymphocytic (PLL)

34
Q

Few exceptions to ‘unknown’ cause:

A

Genetics
Leukemoge
Viral infections
Radiation

35
Q

What are leukemogens?

A

Chemicals causing bone marrow depression and aplasia predispose to leukemia later on (Ex. benzene, chloramphenicol, sulfa drugs, insecticides, antineoplastics)

36
Q

How do viral infections cause leukemias?

A

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
Q

Proto-oncogenes are normal genes which become altered by mutation to become

A

oncogenes (genes that cause cancer mutations)

38
Q

2 examples of mutated versions of proto-oncogene

A

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
Q

Aneuploid:

A

chromosome number that is abnormal

40
Q

Tumor suppressor genes code for

A

proteins which resist malignancy

41
Q

Lab evaluation steps

A
  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
Q

Minimal residual disease (MRD) is detected via cytogenic studies (PCR and FISH) to detect:

A

lowest level of disease detectable in patients who are in continous clinical remisssion

43
Q

What is the minimum % of blasts in bone marrow required for acute diagnosis in FAB system?

A

30%

44
Q

What is the minimum % of blasts in bone marrow required for acute diagnosis in WHO system?

A

20%

45
Q

Methods are sensitivity to

A

levels of tumor burden (amount of cancel cell present in pts body)

46
Q

Treatment must start with a good and accurate:

What are the two goals?

A

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
Q

Four factors playing roles in prognosis & treatment modalities are the patients:

A

Pretreatment health status
Age
Concurrent infection
Abnormal cytogenetics

48
Q

The younger the patient & the less symptomatic, the greater the

A

response to therapy likely will be

49
Q

Categories of leukemia therapy:

A
  1. Chemotherapy
  2. Radiation therapy
  3. Supportive therapy
  4. Targeted therapy
  5. Stem cell transplantation
50
Q

Describe the first line of leukemia therapy and its three stages of therapeutic strategy

A

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!)

  1. Consolidation – low dose chemo. To prevent recurrence
  2. Maintenance – of remission
51
Q

Describe the 2nd line of leukemia therapy

A

Radiation; Produces unstable ions that damage cancer cells’ DNA
Used for localized malignancies

52
Q

Describe the 3rd line of leukemia therapy

A

-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
Q

Describe the 4th line of leukemia therapy

A

Targeted therapy: Monoclonal antibodies which bind directly to affect cell, activates complement, and cell lysis

54
Q

Describe the best, but last line of leukemia therapy

A

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
Q

What are the three types of donors for BMT, or SCT?

A
  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
Q

Common clinical symptoms of all leukemias (to a greater or lesser degree), due to (5)

A

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
Q

Leukemoid reaction

A

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
Q

Leukoerythroblastic reaction (aka. Leukoerythroblastic anemia, or Leukoerythroblastosis)

A

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
Q

What is the LAP stain?

A

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
Q

How can we differentiate leukemoid reaction vs CML?

A

LAP stain!!!

61
Q

LAP is ____ in early leukemia

A

decreased; because leukemic neutrophils are too abnormal to expresses the LAP that normal mature bands & segs would

62
Q

LAP is ___ in leukemoid reaction due to left shift

A

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
Q

Normal LAP score?

A

15-170