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Pathobiology of Neoplasia > Leukemia > Flashcards

Flashcards in Leukemia Deck (28):
1

Pathobiology of Leukemia

• Cell arrest in early phase of maturation
• Accumulation of immature cells (Blasts)
• Abnormal proliferation of blasts
• Crowding of marrow elements





2

Etiology of Leukemia

*Cause is unknown
-Related to genetic disorders
 -Down's syndrome, Bloom's syndrome, Fanconi's sarcoma, Klinefelters syndrome
-55-78% of patients have ACQUIRED chromosome abnormalities
-XRT (atomic bomb survivors)
-Chemicals (Alkylators & antibiotics)
-Chemotherapy (20-25% of cause)
• -Etoposide & Topoisomerase II inhibitors

Viruses:
 Adult T-cell leukemia & HTLV-1 virus

3

Epidemiology of Leukemia

Most common type in adults is AML and CLL

Over 1/2 of cases are acute

Increasing incidence

4

Clinical Manifestations of Leukemia

Caused by:
• Increased proliferation of blasts in blood forming organs
• Infiltration of blasts into other organs
• Decrease in normal leukocytes, erythrocytes & thrombocytes
• displayed by Granulocytopenia, Anemia, Leukemic Infiltrates, Thrombocytopenia 

*Signs & symptoms usually present for

5

Diagnostic Tests for leukemia

Bone Marrow biopsy is standard
-AML is Myeloid line of cells (myelocytes)
-ALL is Lymphoid line of cells (lymphocytes)
-Usually Hypercellular
-Auer rods are diagnostic of AML

Cytogenetic studies
--2/3 of pt's have chromosomal abnormalities 
prognostic indicators
Flow cytometry
-AML vs. ALL
-lymphoid & myeloid markers= biphenotypic

*Peripheral smear may show blasts


6

Classification of Leukemia

AML
-malignant clone of myeloid, monocytes, erythroid or megakaryocyte

M1 (Acute Myelocytic Leukemia)
-most common type

M3 (Acute Promyelocytic Leukemia)
• high risk of DIC; best response/prognosis at 95%

-M4 (Acute Myelomonocytic Leukemia)
-extra medullary infiltration 

M5 (Acute Monocytic Leukemia)
-extra medullary infiltration 

-M7 (Acute Megakaryocytic Leukemia)
◦ rare disease from platelet precursor line



7

Classification Systems for Leukemia

FAB
• Morphology, cell stains and flow cytometry
• Myeloid M0-M7
◦ MDS vs. AML threshold= 30% blasts
◦ Lymphoid L1-L3

WHO
• uses prognostic factors
◦ molecular markers
◦ chromosome translocations
◦ dysplasia present?
◦ 17 subclasses
◦ MDS vs. AML threshold= 20% blasts




8

AML w/ characteristic genetic abnormalities

-chromosome 8 and 21 translocations
-chromosome 15 and 17 translocations
-chromosome 16 inversion
◦ Most favorable; no transplant in first remission

9


AML w/ multi lineage dysplasia


patients with MDS or MPD 


10

AML and MDS (therapy related)





prior treatment w/ chemo and/or XRT





11

AML; not otherwise categorized





other subtypes





12

Acute leukemia w/ ambiguous lineage


-both myeloid and lymphoid cells 
-or not distinguishable
-Mixed or biphenotypic 


13

AML Treatment

Induction
-normally 7+3

Evaluation
-Day 14 BM Bx
-CR =

14

Classification of APL and treatment

Also called M3
Chromosome 15 and 17 translocation
Treated with Arsenic and Atra
Monitored by PML-RAR alpha

15

Description of ALL

Originates in thymus, lymph nodes and bone marrow
T-cell, B-cell, or NK cell
CNS disease common
Can be Philly positive (BCR-ABL testing)

16

ALL Presentation

Lymphadenopathy
Splenomegaly

17

Induction therapy for ALL?

HyperCvad x8 treatments
A: Cytoxan, vincristine, doxorubicin, decadron
B: MTX, cytarabine, IT MTX
Also use IT Cytarabine

18

Blinatumomab

TX of Relapse, refractory, Philly negative ALL
CD19 positive cells are attacked by cytotoxic T-cells
*CD19 is a specific B-cell marker

19

Treatment of Philly + ALL

25% of ALL diagnosis
Need allo transplant
Tx with TKI: dasatinib, ponatinib

20

How is MDS scored?

The IPSS
-blast percentage
-cytogenetics
-# of cell types affected in circulating blood
*Higher score=decreased survival rate (I.e. >2.5)

21

Treatment for MDS

Observation
Vidaza
Growth factors (procrit)
Revlimid
Decitabine
Clinical trial
HSCT w/ HLA identical donor

22

Description of CML

95% of pts Philly +
Chromosome 9 and 22 translocation
BCR-ABL +

23

S/S of CML

LUQ pain
Early satiety
Bone, joint pain
Abd fullness
*MANY ARE ASYMPTOMATIC

24

Diagnosis of CML

BM BX for FISH and BCR-ABL
-elevated WBC
-Decreased Hgb
-elevated platelets in chronic phase

25

Treatment for CML

TKI's
-ponatinib
-dasatinib
-imatinib

26

Description of CLL

Also called Small lymphocytic lymphoma
Accumulation of NORMAL appearing lymphocytes in marrow, spleen, liver and nodes
*RAI staging system

27

Treatment of CLL

Fludarabine
Bendamustine
Ibrutinib (improves prognosis when used in conjunction)
Ofatumumab

28

Hairy cell Leukemia

Chronic
Presents with pancytopenia and severe splenomegaly
Tx'd with cladrabine
Oral drugs for BRAF mutation