Brainscape's Knowledge GenomeTM

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


See full index

Heme > Myeloproliferative Diseases > Flashcards

Myeloproliferative Diseases Flashcards

1
Q

What are the myeloproliferative syndromes?

A

Chronic granulocytic leukemia
Idiopathic myelofibrosis
Primary Thrombocythemia
Polycythemia Rubra Vera

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

What is the incidence of CML per 100,000?

A

1-2 (typical of all myelogenous leukemias)

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

What is the median presentation age of CML?

A

45-55yrs

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

Does incidence of CML increase with age?

A

Yes. 12-30% are >60

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

What is the ratio of male to female patients with CML?

A

1.3-1

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

How are most CML’s diagnoses at presentation?

A

50% by routine lab tests

85% diagnosed in the chronic phase

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

What are the etiologic factors associated with chronic granulocytic leukemias?

A

Idiopathic
Radiation exposure
Chemical exposure

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

What symptoms are seen in pts. with CML?

A

Fatigue, weight loss, abdominal fullness, easy bruising or bleeding, abdominal pain

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

What are the physical findings seen in pts. with CML?

A

Splenomegally, hepatomegally, sternal tenderness, purpura, retinal hemorrhage, fever, and palpable lymph nodes (pretty rare)

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

Is uric acid level elevated in CML?

A

Yes

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

Do you get a high or low leukocyte alkaline phosphatase score in CML?

A

Low

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

Do you see high or low B12 levels with CML?

A

Elevated

B12 binding protein also elevated. Transcobalamine 1

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

What are the clinical phases of CML? What are the survival times associated with each?

A

Chronic phase: 5-6 yrs stabilization
Accelerated phase: 6-9mo median duration
Blast Crisis: 3-6mo survival

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

What is the name of the abnormal chromosome found in CML? Who discovered it?

A

Philadelphia. Janet Rowley in 1960

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

What translocation is seen in the Ph chromosome?

A

9/22

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

In how many pts. with CML is the Ph chr found?

A

95% of pts. Ph chr. is present in 100% of RBCs, WBCs, monocytes, and platelets

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

What happens as a results of the 9,22 translocation?

A

Fusion protein Bcr-Abl with tyrosine kinase activity

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

Which phase of pts. with CML is most likely to have leukemia free survival with BM transplant? Least likely?

A

Chronic phase most likely to do well. Blast crisis phase pts. most likely to do the worse

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

What drug is used as a targeted therapy for CML?

A

Imatinib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does Imatinib do?

A

Blocks ATP from binding Bcr-Abl tyrosine kinase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Imatinib has steady state PK at what dosing?

A

400-600mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How is the bioavailibility of imatinib?

A

98%. It’s rapidly and completely absorbed after oral administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the hematologic response of CML pts. in chronic phase that receive imatinib?

A

100% rapid response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Is there a 100% hematologic response in pts. with blast crisis myeloid or blast crisis lymphoid CML?

A

No.
Blast myeloid=56%
Blast lymphoid=70%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the overall survival of pts. receiving imatinib for 72mo?

A

Good, somewhere between 90-100%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What’s the estimated annual rate of treatment failure for CML with imatinib?

A

Very low. Between 3.3%-7.5% during the first two yrs of treatment and even lower percentages of treatment failures from 3-5yrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What gives clinical resistance to Imatinib?

A

Mutation T-3151- BM transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are 2nd generation molecules to treat CML?

A

Dasatinib and Nilotinib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What hormone is crucial in RBC formation?

A

Epo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How is Jak2 important in RBC formation?

A

It’s bound to the EpoR and activated upon Epo binding to the receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What pathway is activated with Epo signaling? What does signaling result in?

A

Signaling of EpoR starts with activation of Jak2, then activation of STAT, Map-kinase, Pi-3 kinase, and AKT. Results in proliferation and differentiation of RBC precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the mutation found in Jak2 associated with myeloproliferative diseases?

A

Guanine to thymidine mut. results in substitution of val to phe at codon 617, within the pseudokinase domain of Jak2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Jak2 mutations are found in which diseases?

A

PV: 95%
ET:50-70%
MF: 40-50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Can homozygous mutations be found in some pts?

A

Yes. Pts. with PV can have homozygous Jak2V617F which are the result of recombination and duplication of the mutant allele

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the median age for idiopathic myelofibrosis (PMF)? Male female ratio? Incidence?

A

65yrs. 1:1 male to female incidence. 1.4 cases per 100,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What causes PMF?

A

Myeloproliferation with granulocytic hyperplasia and megakaryocytosis. Marrow fibrosis with increased collagen types I, III (most), IV, and V

37
Q

Fibrosis in PMF correlates closely with what?

A

Increases dysmorphic megakaryocytes in the marrow

38
Q

Fibrosis in PMF is the result of what?

A

Cytokines released from abnormal megakaryocytes

39
Q

What are the clinical symptoms of PMF?

A

Fatigue, weakness, SOB, palpitations, weight loss, dragging sensations in LUQ, early satiety, pain in L shoulder, bone pain in the lower extremities

40
Q

What are the physical findings in PMF?

A

Splenomegally (100%), hepatomegally (75%), muscle wasting, peripheral edema, purpura, bone tenderness, neutrophillic dermatosis

41
Q

What are the lab findings in PMF?

A

Early on: thrombocytosis

Bizarre changes in Megs.
Ansiocytosis, poikilocytosis, tear drops Nucleated RBCs and WBCs
WBC elevated
Marrow: increased fibrosis and abnormal megs

42
Q

Where can fibromatopoietic extra medullary tumors occur in PMF?

A

Anywhere

43
Q

What are other symptoms of PMF?

A

portal HTN, results in ascites, esophageal and gastric varices. Osteosclerosis: proximal femur and humerus, pelvis, vertebral bodies, ribs and skull

44
Q

What are some therapies for PMF?

A

androgens, procrit, hydroxyurea, thalidomide, lenalimide

45
Q

For lenalimide, del 5q31 may achieve what?

A

Remissions accompanied by marked reduction in numbers of cells bearing marker chr. and JAK2V617F

46
Q

What is radiation therapy used for in PMF?

A

Splenic pain, massive spleen enlargement, focal bone pain, and extra medullary tumors

47
Q

When are splenectomies done in PMF pts?

A

painful enlargements, excessive transfusions, severe thrombocytopenia, and portal HTN

48
Q

Can BM transplant cure PMF?

A

Yes

49
Q

Why don’t most pts. with PMF have BM transplants?

A

B/c they are too old or have co-morbidity

50
Q

Can acute leukemia cause death in idiopathic myelofibrosis?

A

Yes (25%)

51
Q

What things can cause secondary thrombocytosis?

A

trauma, surgery, acute bleeding, Fe deficiency, infection, chronic inflammatory disease, neoplasia, splenectomy

52
Q

What are Characteristics of secondary thrombocytosis?

A

Generally have no splenomegally
Extreme platelet elevations don’t r/o secondary thrombocytosis
Platelet morphology and function is normal
Bone marrow megakaryocytes are normal
Thrombosis and bleeding is rare

53
Q

What are Special cases of secondary Thrombocytosis

A

Rebound thrombocytosis and splenectomy

54
Q

What’s associated with rebound thrombocytosis?

A

Recovery from marrow suppression

May stay elevated for 10-14 days

55
Q

What would you see in thrombocytosis from splenectomy?

A

May be greater than 1 million one week after operation. May not return to normal for 2 months

56
Q

What is the Clinical epidemiology of ET?

A

It is the least common of the MPDs :0.5 per 100,000 in the U. S. Age at diagnosis is 50-60 years. 1:1 male to female ratio

57
Q

What are the clinical feats of ET?

A

Spenomegaly in 40% of patients
Aortic and mitral valvular leaflet thickening or vegetations(similar to non-bacterial thrombotic endocarditis)
Leukemic transformation is less than the other MPDs
Fever, night sweats and weight loss are uncommon.

58
Q

What are the serum TPO levels in ET?

A

Serum Thrombopoetin levels are normal or elevated and does not coorelate with the platelet count

59
Q

Are most forms of secondary thrombocytosis associated with elevated levels of TPO?

A

Yes

60
Q

What are major risk factors for thrombosis in pts. with ET?

A
  1. previous thrombosis
  2. advanced age
  3. associated cardiovascular risk factors(smoking)
61
Q

What increases the risk for bleeding in pts. with ET?

A

platetlets >1,500,000

62
Q

Where are bleeding sites seen in pts. with ET?

A

Mucosal and GI tract, cutaneous, genitourinary, and post-op

63
Q

What are Thrombotic complications of ET?

A

50% of patients have at least one episode in 9 years of followup

64
Q

Are arterial or venous thrombosis more common in ET?

A

Arterial thrombosis is more frequent than venous. Venous complications usually of the lower extremities

65
Q

Where are the arterial sites of thrombosis in ET?

A

CVA, peripheral vasculitis, coronary artery disease

66
Q

What are some other complications of ET?

A 
Placental insufficiency
	spontaneous abortions
	fetal growth retardation
	premature deliveries
	abruptio placenta
Budd-Chiari syndrome
67
Q

What is the treatment of ET?

A

Hydroxyurea: Cycle specific agent interfering with S phase progression of DNA synthesis

68
Q

How is hydroxyurea given?

A

Oral tablet

69
Q

What are the associated toxicities with hydroxyurea?

A

leucopenia, anemia, thrombocytopenia

70
Q

What is another drug treatment of ET?

A

Anagrelide

71
Q

What does Anagrelide do?

A

Interfers with terminal differentiation of megakaryocytes

72
Q

How is Anagrelide given?

A

Oral

73
Q

What are the associated toxicities with Anagrelide?

A

Thrombocytopenia, congestive heart failure, headaches

74
Q

What are causes of excess production of Epo?

A

Cellular hypoxia, Local renal hypoxia.

75
Q

WHat are causes of secondary polycythemia?

A

Renal vascular impairment and tumors.

76
Q

What are epidemiological characteristics of Characteristics of polycythemia rubra vera (PRV)?

A

2.8/100,000 men
1.3/100,000 women
Commonly presents in 50-60th decade
1.5% risk of leukemic transformation in 18 years

77
Q

What is the median survival of PRV?

A

13.9 years

78
Q

What are symptoms of PRV?

A

Headache, weakness, pruritis!, dizziness, sweating, visual disturbances, weight loss, parathesias, dyspnea, joint symptoms, epigastric distress

79
Q

What are the lab findings in PRV?

A 
Hematocrits of 55-65
2/3d have leucocytosis
2/3d have basophilia
LAP score and B12 levels elevated in 70%
Platelets elevated in ½ patients 
Marrow hypercellularity
Absence of iron stores in most patients
80
Q

How many PRV pts. have thrombotic events?

A

1/3d. 3/4th are arterial and 1/4th are venous

81
Q

What happens with the majority of arterial episodes in PRV?

A

Ischemic strokes and TIAs

82
Q

How often is Budd Chiari seen in PRV?

A

10%, but it is fatal

83
Q

What is another thrombotic complication of PRV?

A

Erythromelalgia

84
Q

What is Erythromelalgia?

A

warm extremities, painful digits, burning sensation, may lead to necrosis of the digits

85
Q

What is the therapy for PRV?

A

Phlebotomy. Take off 500 ml of blood at intervals of 2-4 days and then back off to weekly and then monthly when Hmt stabilizes. And Myelosuppresive agents when platelets or WBC rises or for severe pruritis

86
Q

What is the key treatment for PRV?

A

Phlebotomy

87
Q

What is the spent phase of PRV?

A

Anemia
Leucocyosis
Marrow fibrosis
Enlarging spleen

88
Q

At the spent phase, PRV mimics what?

A

MF

89
Q

Can you treat ET, PRV and MF with aspirin?

A

Yep. Use low dose aspirin

Heme (38 decks)

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