Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Oncology > 9 - Chronic Myeloid Leukemia and Myeloproliferative Neoplasms > Flashcards

9 - Chronic Myeloid Leukemia and Myeloproliferative Neoplasms Flashcards

1
Q

Myeloproliferative Neoplasms - Specific disorders

A 
Chronic Myeloid Leukemia
Polycythemia Vera
Essential Thrombocytosis
Primary Myelofibrosis
Chronic Eosinophilic Leukemia
Systemic Mastocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Myeloproliferative Neoplasms

A

Excess of mature myeloid cells
Usually of single lineage
Often some overlap
Activating mutations in Tyrosine Kinases are common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Chronic Myeloid Leukemia - Epi

A

Presents 45 - 55, but incidence increases with age. 12 - 30% are >60
M>F (1.3:1)
50% diagnosed by routine labs
85% diagnosed during chronic phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Chronic Myeloid Leukemia - Symptoms

A

Fatigue
Abdominal fullness
Fever, Chills, Sweats, Weight Loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Chronic Myeloid Leukemia - Physical Findings

A

Hepatosplenomegaly

Ecchymoses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Chronic Myeloid Leukemia - Common Labs

A

Increased mature and immature myeloid cells
Basophilia
Anemia
Thrombocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Chronic Myeloid Leukemia - Peripheral Blood Smear

A

Immature cells in the myeloid lineage

More committed than the blast cells, but still immature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Chronic Myeloid Leukemia - Bone Marrow

A

Hypercellular with increased Myeloid-to-Erythroid ratio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Chronic Myeloid Leukemia - Genetics

A

The Philadelphia Chromosome
t(9;22)
BCR-ABL gene fusions

Quantitative Reverse Transcriptase PCR detecting BCR-ABL can evaluate disease burden

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Chronic Myeloid Leukemia Response to Therapy - Hematologic Response

A

Complete:
Normal peripheral blood count
WBC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Chronic Myeloid Leukemia Response to Therapy - Cytogenetic Response

A

Major:
Complete: 0% Ph+ cells
Partial: 1% - 35% Ph+ cells

Minor: 36% - 95% Ph+ cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Chronic Myeloid Leukemia Response to Therapy - Molecular Response

A

MR3 (“Major”): >3 log reduction in BCR-ABL transcripts from baseline
MR4.5 (“Complete”): >4.5 log reduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CML Survival

A

4ish years median surivval

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CML Phases

A

Chronic (Median 4 -6 years)
Accelerated (Variable duration)
Blast Crisis (Median survival 3 - 6 months)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CML - If a patient responds to Interferon treatment

A

The prognosis from then on is usually good!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CML - If a patient doesn’t respond to Interferon treatment

A

The prognosis is as if they had no treatment at all

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The only way to cure CML

A

Allogeneic Stem Cell Transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Imatinib - Mechanism of action

A

Binds to the ATP binding site of ABL, preventing the transfer of phosphate groups to other proteins, blocking downstream signaling!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Imatinib - Side Effects

A

Bone marrow suppression:
Leukopenia
Anemia
Thrombocytopenia

GI:
Nausea
Vomiting
Diarrhea

20
Q

Imatinib - Metabolism

A

Well absorbed PO
Hepatic metabolism
Cytochrome P450
Majority excreted in biliary tract as metabolites with only a small percent unchanged
Doses must be adjusted in patients with severe liver disease.

21
Q

CML - Patients who attain MR3 with Imatinib treatment

A

Have better survival

22
Q

What can cause imatinib resistance?

A

DDIs
Adherence issues
Multiple copies of the Ph chromosome
Mutations in ABL

23
Q

Clinical indications of Imatinib and other TK inhibitors

A 
Ph+ diseases (ABL)
CML
Ph+ ALL
C-kit diseases
GIST
24
Q

Polycythemia Vera

A

Elevated Hgb/Hct on lab testing

Thrombosis

25
Q

Polycythemia Vera - Symptoms

A

Pruritus - especially after showering
Plethora (Ruddy complexion)
Abdominal fullness/early satiety (splenomegaly)

26
Q

Polycythemia Vera - Most common mutation

A

JAK2 in the Pseudokinase domain

Results in downstream anti-apoptotic signaling through JAK2 in the absence of Erythropoietin

27
Q

Polycythemia Vera - Bone Marrow

A 
Moderate to marked hypercellularity
Increased hematopoiesis
Maturation intact
Large clustered megakaryocytes
Decreased/absent iron stores
Increased reticulin fibers in a minority of cases
28
Q

Polycythemia Vera - Diagnostic criteria

A

Major:
Hgb > 18.5 in men or > 16.5 in women or other evidence of increased RBC volume
Presence of JAK2V617F or JAK2 exon 12 mutation

Minor:
Hypercellular bone marrow with trilineage hematopoiesis
Low serum erythropoietin
Endogenous enrythroid colony formation in vitro

Diagnosis requires both major criteria of elevated Hgb & 2 minor criteria

29
Q

Polycythemia Vera - Differential

A 
Chronic Hypoxia (Altitude, cigarettes, sleep apnea, pulmonary disease)
Erythropoietin abuse
Familial erythrocytosis (mutation in Epo R)
30
Q

Polycythemia Vera - Clinical Course

A

Overall mortality 3% per year
Thrombosis (increased by age >65 and prior thrombosis)
Bleeding
Transformation to AML (influenced by duration of disease)
Myelofibrosis (“spent phase”) - More common in age>70

31
Q

Polycythemia Vera - Management

A

Therapeutic phlebotomy (Maintain Hct

32
Q

Polycythemia Vera - Management - Cytoreduction

A

Consider cytoreduction if:
Patient is intolerant of phlebotomy
Thrombosis develops
Symptomatic or progressive splenomegaly

age 40: Hydroxyurea (Hydroxycarbamide)

33
Q

Essential Thrombocythemia (Essential Thrombocytosis) - Clinical presentation

A

Elevated PLT on labs
Thrombosis
Symptoms:
Pruritus - Especially after showering
Erythromelagia (Severe pain in hands/feet)
Abdominal fullness/early satiety (splenomegaly)

34
Q

Essential Thrombocythemia - Genetics

A

50% of cases - JAK2 mutation, similar to Polycythemia vera
Why the same mutation leads to two diseases is unclear, but may have to do with allele burden.
5% have point mutations in mpl

35
Q

Essential Thrombocythemia - Diagnosis

A

Sustained platelet count > 450,000/μL for at least 2 months

Bone marrow showing primarily megakaryocytic proliferation

No evidence of WHO diagnosis of Polycythemia Vera, Primary myelofibrosis, CML (BCR-ABL translocation), MDS or other myeloid neoplasms

JAK2V617F mutation or other clonal marker (mpl mutation) or in the absence of a clonal marker, no evidence of reactive thrombocytosis

36
Q

Essential Thrombocythemia - Differential Diagnosis

A 
Reactive elevation of platelet count:
Iron deficiency
Inflammation/Infection
Surgery
Splenectomy
Connective tissue disease
Metastatic cancer
Lymphoproliferative disease

Polycythemia Vera
Chronic Myeloid Leukemia

37
Q

Essential Thrombocythemia - Clinical Course

A

Uncertain if ET compromises life span
Thrombosis (higher in patients > 60 w/previous history of thrombosis, cardiovascular risk factors, JAK2V617F mutation)
Bleeding - Higher in patients with plt>1,500,000
Myelofibrosis (4 - 8% at 10 years)
AML (1% in untreated patients)

38
Q

Essential Thrombocythemia - Management

A

All: Aggressive management of cardiovascular risk factors

Low risk: (Age 60, prior thrombosis, cardiovascular risk factors)
Low dose aspirin + hydroxyurea
Consider anagrelide or interferon alfa if hydroxyurea intolerant

39
Q

Primary Myelofibrosis - Clinical Presentation

A

Abdominal fullness (due to splenomegaly)
Splenomegaly (due to extramedullary hematopoiesis)
Symptoms of anemia (Fatigue, pallor, dyspnea on exertion)
Bleeding/bruising
Infection
Cachexia

40
Q

Primary Myelofibrosis - Bone marrow

A

Hypercellular
Megakaryocytic hyperplasia
Pleomorphism of megakaryocytes
Granulocytic/erythroid maturation intact
Fibrotic phase - Loss of hematopoiesis (megakaryocytes spared)
Osteosclerosis - Increased osteoclasts and osteoblasts

41
Q

Primary Myelofibrosis - Peripheral blood smear

A 
Teardrop RBCs
Leukoerythroblastic features (peripheral blood looks like marrow)
42
Q

Primary Myelofibrosis - Major Diagnostic Criteria

A

Major:
Hypercellular marrow with megakaryocytic atypia and reticulin and/or collagen fibrosis

WHO diagnostic criteria for Polycythemia Vera, CML, ET, MDS or other myeloid neoplasms excluded

Presence of JAK2V617 or other clonal marker OR in the absence of a clonal marker, no evidence of reactive fibrosis

Minor:
Leukoerythroblastosis
Elevated LDH
Anemia
Splenomegaly

Diagnosis requires all major criteria AND 2 minor criteria

43
Q

Primary Myelofibrosis - Clinical Course

A

Variable life expectancy - Average 5 years
Months to decades

Risk factors:
Age > 65 yo
Hgb  25k/μL
Blasts > 1%
Constitutional symptoms
RBC transfusion dependence
Unfavorable karyotype (eg +8, abnl 7 or 5, 12p-, inv3, 11q23 rearrangement)
Plt
44
Q

Calreticulin

A

Target of autoantibodies in SLE and Sjogrens
Major calcium storage protein in the ER
Inhibits binding to Glucocorticoid Response Element in the nucleus
Regulates gene transcription

45
Q

Primary Myelofibrosis - Calreticulin mutation

A

Better survival than with JAK2 mutation or mpl

46
Q

Primary Myelofibrosis - Management

A

Supportive measures:
Erythropoietin/transfusions
Hyrdroxyurea
Splenectomy/splenic radiation

Active Therapy:
Stem cell transplant
Thalidomide/corticosteroids
Jak inhibitors

47
Q

Primary Myelofibrosis - Ruxolitinib

A

Reduces splenomegaly and improves survival

Oncology (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions