Brainscape's Knowledge GenomeTM

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


See full index

Heme/Onc > MKSAP 1: Hematopoietic stem cell and their disorders > Flashcards

MKSAP 1: Hematopoietic stem cell and their disorders Flashcards

1
Q

Name the bone marrow failure syndromes

A

Aplastic anemia
Pure red cell aplasia
Neutropenia

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

What are the characteristics of aplastic anemia?

A

a condition characterized by pancytopenia with associated neutropenia, anemia and thrombocytopenia and a severely hypocellular bone marrow (<10%)

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

What the main etiologies of aplastic anemia?

A

Toxic, viral or autoimmune mechanisms

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

Define severe plastic anemia from very severe aplastic anemia?

A

Severe aplastic anemia has two or more of the following:
- ANC 200-500/uL
- Platelet count < 20K/uL
- absolute reticulocyte count <40K/uL
Very severe aplastic anemia has two or more the above except with ANC <200

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

What are some drugs that can cause aplastic anemia?

A

NSAIDs, beta-lactam abx, antiepileptic drugs and psychotropic meds

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

What is the dominant cause of adult AA?

A

autoimmunity as autoreactive T cells attack pluripotent HSCs and cause aplasia

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

What is first line therapy for aplastic anemia?

A

cyclosporine and antithymocyte globulin leads to control in 70% of adults. Allogeneic HSCT is a potentially curative therapy and should be considered for those younger than 50 with compatible donors

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

What are the 3 disorders that are acquired defects of the hematopoietic stem cell?

A

aplastic anemia
paroxysmal nocturnal hemoglobinuria
myelodysplastic syndromes

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

What is PNH?

A

Acquired disorder in which erythrocytes lack membrane proteins CD55 and CD59 required to stabilize complement leading to episodic intravascular hemolysis

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

What is the cardinal feature of pure red cell aplasia?

A

Severe anemia without an adequate reticulocyte response. Examination of bone marrow shows an absence of erythrocyte precursors

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

What is the mechanism for PRCA?

A

predominantly T cell autoimmunity or direct toxicity to erythrocyte precursors

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

List causes of PRCA

A 
Parvovirus B19
Thymoma
Autoimmune disease
Lymphoid lukemia and lymphomas
Solid tumors
Drugs (phenytoin, isoniazid)
Pregnancy 
Anti-EPO antibodies in patients receiving EPO
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What specific subset of patients are susceptible to parvovirus B19 infection causing PRCA? What treatment may they require?

A

sickle cell anemia patients
Can cause severe anemic crisis
IVIG may hasten viral clearance

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

What diagnostic test is required to diagnose PRCA? What else does it exclude?

A

Bone marrow examination

Also excludes secondary causes of PRCA such as CLL or non-Hodgekin lymphomas

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

How do leukemias and lymphomas cause PRCA?

A

Immune mediated mechanisms

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

Name the T cell lymphoproliferative disorder that is associated with PRCA, is associated with RA, diagnosed by peripheral blood smear and shows lymphocyte CD57 positivity on flow cytometry
How can it be treated?

A

large granular lymphocytosis

Treated with methotrexate

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

define felty syndrome

A

clinical triad of RA, splenomegaly and neutropenia

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

How is thymoma excluded as a cause of PRCA?

A

CT scan of the chest

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

How are idiopathic causes of PRCA treated?

A

Immunosuppression with prednisone either administered alone or with cyclosporine or cyclophosphamide

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

What are the possible general causes of isolated neutropenia?

A

Hereditary, toxic or immune causes

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

What are the general categories of toxicities to cause neutropenia?

A

viral, bacterial or meds

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

Name the viruses that can cause neutropenia?

A

Acute HIV, CMV and EBV

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

What specific bacterial infections can cause neutropenia?

A

Rickettsial infection or overwhelming bacterial infection

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

What meds can cause neutropenia?

A

Cytotoxic chemos, NSAIDs, carbamazepine, phenytoin, PTU, cephalopsorins, Bactrim and psychotropic drugs

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

What immune related disorders can cause neutropenia?

A

Connective tissue disease such as SLE and RA

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

What is the main difference between aplastic anemia and the myelodysplastic syndromes?

A

Dysplastic (difficult formation) marrow of MDS is most commonly hypercellular. A full bone marrow yields low blood counts bc cells are ineffectively formed and limited survival

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

What are some etiologies of MDS

A

Past radiation or chemo but more commonly a primary process

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

What is the dreaded complication of MDS

A

Conversion to AML

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

LEFT OPEN FOR WHO Classification of MDS

A

LEFT OPEN FOR WHO Classification of MDS

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

What are patient characteristics to detect MDS?

A

MDS increases with age. Suspect in patients with macrocytic anemia or pancytopenia in whom B12 and folate have been excluded. Basophilic stippling or Howell Jolly bodies and dysplastic neutrophils

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

What is the scoring system used for MDS and what does it incorporate?

A

International Prognostic Scoring System (IPSS-r) weighs percentage of marrow blasts, cytogenetics of the marrow and peripheral blood cytopenias

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

What are the 2 treatment goals for MDS?

A

1) Relieve transfusion dependence

2) Prevent transformation to AML

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

What is the approach with a patient considered low risk MDS?

A

No treatment at all or infrequent transfusions

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

What is the approach with a patient considered high risk or very high risk?

A

Require treatment at diagnosis

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

What are the therapies for MDS?

A

allogeneic HSCT in fit younger patients or chemotherapy such as asacytidine and decitabine

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

Name the myeloproliferative neoplasms

A 
CML
Polycythemia vera
Essential thrombocytopenia
Primary myelofibrosis
Eosinophilia and Hypereosinophilic syndromes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

How do the MPNs present?

A

unusual thromboses, massive splenomegaly

constitutional symptoms such as fevers, chills, weight loss and night sweats

38
Q

What cancer do all MPNs have a gradual connection to?

A

Each has a chronic phase that may progress at varying frequency to AML

39
Q

How might a patient with CML present and what would be seen on peripheral blood smear?

A

Present with constitutional symptoms and splenomegaly , fatigue, early satiety and progressive weight loss
Granulocytic leukocytosis is seen on CBC and earlier myeloid forms such as metamyelocytes, myelocytes and less than 5% blasts are present on peripheral smear

40
Q

What is the main indicator for extreme granulocytic leukocytosis?

A

the leukemoid reactions, >50K WBC

Can also be caused by sepsis and Cdiff

41
Q

What is the genetic cause of CML?

A

The Philadelphia chromosome leading to fusion gene BCR-ABL encoding a mutant tyrosine kinase. Necessary and sufficient to diagnose CML

42
Q

What is the guideline for treatment of CML compared to ET and PMF?

A

Therapy is required at diagnosis otherwise can lead to transitional accelerated phase or progress to an overt blast crisis

43
Q

What are the percentages of leukemias arising from CML?

A

AML (80%)

ALL (20%)

44
Q

What is the treatment for CML?

A

Tyrosine kinase inhibitors
1st gen - imatinib
2nd gen - nilotinib or dasatinib

45
Q

What side effect needs to be monitored for tyrosine kinase inhibitors?

A

QT interval prolongation

46
Q

What are the unique side effects of dasatinib?

A

Pericardial and pleural effusions and associated with pulm arterial HTN
No TKI is safe in pregnancy

47
Q

What are the therapeutic options for CML in pregnancy?

A

Close observation without therapy or interferon alfa

48
Q

Progression of CML is due to medication nonadherence and/or TKI resistance. What new TKI has been approved and what side effects need monitored?

A

Ponatinib overcomes some TKI resistance
Thromboembolic complications
These drugs also cost 100K a year and need assistance obtaining

49
Q

What is polycythemia vera?

A

A disorder of myeloid/erythroid stell cell that causes erythropoietin independence proliferation of erythromcytes, analogous to the Philadephia chromosome in CML
Activating mutation of JAK2 (JAK2 V617F)

50
Q

When is PV suspected?

A

Hgb > 18.5 in men or greater than 16.5 in women after 2nd causes excluded

51
Q

What is the common underlying cause of 2nd erythrocytosis and what is it commonly due to?

A

Elevated erythropoietin level and most common hypoxemia

52
Q

What are some 2nd causes of 2nd erythrocytosis?

A

Hypoxemia: COPD, sleep apnea, congenital heart disease, intrapulmonary shunting, elevated altitude, renal artery stenosis
Elevated erythropoietin: renal cell carcinoma, hepatocellular carcinoma, uterine fibroids

53
Q

What clinical features distinguish MPNs?

A

pruritus after a warm bath, intermittent heat, redness and pain of palms and soles, hepatosplenomegaly, elevated WB and platelets and unusual thormboses

54
Q

What lab findings are classic for PV?

A

Elevated serum B12 causes by increased levels of transcobalamin III produced in proliferating leukocytes
Hyperuricemia as a consequence of DNA turnover

55
Q

What uncommon clots should prompt evaluation for PV?

A

Hepatic vein thrombosis or portal vein thrombosis

56
Q

What are the treatment options for PV?

A

Therapy for PV is required at diagnosis.
Low dose aspirin decreases arterial and venous clot risk
Phlebotomy is the mainstay of therapy and can be used in addition to aspirin in patients younger than 60 years w/o previous thromboembolic event. Goal is Hct <45%
Hydroxyurea can be used in conjunction with phlebotomy in patients older than 60 years or those with previous thromboembolic events

57
Q

What can be seen in PV patients in response to their treatment and in peripheral blood smear as PV progresses to fibrotic stage?

A

Decreasing phlebotomy or hydroxyurea requirements and increasing splenomegaly.
Peripheral smear with teardrop cells, nucleated erythrocytes and immature myeloid forms

58
Q

When is essential thrombocytopenia suspected?

A

Platelet count of greater than 600K detected on 2 or more occasions at least 1 month apart in the absence of secondary causes

59
Q

What are the secondary causes of ET and what is the most common?

A

IDA is the most common followed by reactive states due to infection or inflammation

60
Q

What symptoms may be present in ET?

A

Digital ischemia, erythromelalgia, tranient ischemic attack, visual disturbances, venous thromboembolism, or bleeding

61
Q

What score can be used ot risk stratify patients with ET?

A

The INternational Prognostic Score for ET. Many patients may be observed

62
Q

What patients are considered low risk with ET and can be observed?

A

younger than 60 years, no previous thrombosis, WBC < 11K

63
Q

What treatment options are indicated for ET?

A

Platelet lowering therapy is indicated for any patients at high risk. Hydroxyurea is well tolerated in older patients and considered 1st line in nonpregnant patients.
Anagrelide is an agent that prevents megakaryocyte budding but may cause fluid retention and exacerbation of CHF
Interferon alfa is the only platelet lowering agent safe in pregnancy
Plateletpheresis may be employed emergently to temporarily decrease platelet counts in symptomatic patients with extreme thrombocytosis, usually greater than 1 million

64
Q

How does ET compare to other MPN in terms of AML and symptoms?

A

ET is the least likely to progress to AML or secondary fibrosis and least likely to present with symptomatic splenomegaly or constitutional symptoms

65
Q

What is primary myelofibrosis?

A

Is an MPN that does not present with a dominant blood count elevation rather it is a clonal myeloid disorder characterized by abnormal proliferating megakaryocytes that prodcue excess fibroblast growth factor which causes marrow fibrosis and leads to extramedullary hematopoiesis

66
Q

What can be describe on a bone marrow aspiration in PMF? What happens to LDH and uric acid?

A

“dry tap”

LDH and uric acid are elevated

67
Q

What are the extramedullary hematopoesis sites?

A

Spine or lymph nodes

68
Q

What symptoms can be seen in PMF?

A

fever, chills, night sweats, and malaise, early satiety, weight loss and abdominal discomfort

69
Q

When is treatment required in PMF and what does it entail?

A

Treatment required for symptomatic splenomegaly, worsening cytopenias and constitutional symptoms
Allogeneic HSCT in younger patients
Treatment is palliative otherwise, splenectomy is perilous
Hydroxyurea
Jak2 inhibitor ruxolitinib

70
Q

What is the differential for eosinophilia?

A

C - collagen vascular disease (Churg Strauss)
H - helminthic infection (strongyloides)
I - idiopathic hypereosinophilic syndrome
N - neoplasia (lymphomas)
A - allergy, atopy, asthma, also drug induced (carbamazepine, sulfonamides)

71
Q

What are hypereosinophilic syndromes? Describe primary and secondary

A

Disease characterized by eosinophilia with a count > 1,500 and eosinophilic infiltrates of the tissues resulting in organ damage in addition to systemic symptoms such as fever, chills, night sweats and weight loss
Primary - an MPN with moelcular activation of platelet derived growth factor receptor without a known stimulating factor
2nd - polyclonal expansion in response to identified stimulus such as parasitic infection

72
Q

What is the medication indicated for eosinophilic syndromes?

A

Glucocorticoids have dramatic lytic effect but long term use in HESs is problematic

73
Q

What is the greatest risk factor for AML?

A

Age, mean age of presentation is 67

74
Q

What is the diagnostic criteria for AML?

A

Requires 20% or more myeloblasts in either the peripheral blood or the marrow

75
Q

What are the symptoms on labs in AML?

A

Anemia, thrombocytopenia and neutropenia

90% myeloblastic, 10% lymphoblastic in adults; reverse in children

76
Q

What syndrome can develop in AML and what intervention needs to be considered>?

A

Hyperleukocytosis syndrome including hypoxemia and mental status change from stasis of immature cells in small capillary networks. Leukapheresis

77
Q

What are the acute decisions that need to be determined acutely in suspected acute leukemia?

A
  • Confirm acute leukemia
  • AML vs. ALL (auer rods on blood smear, confirmed on flow cytometry)
  • Exclude APL (Clinically suspected with DIC, classically with promyelocytes and prominent Auer rods, microgranular variant evaluated by flow cytometry; administer ATRA)
  • AML - not APL (Begin induction therapy with cytosine arabinoside and an anthracycline)
  • ALL (Philadelphia chromosome + or -)
78
Q

What is the greatest influence on survival in AML?

A

genetic profile of the leukemic cells

79
Q

What are the favorable AML genetic risk profiles?

A

T(8;21)
inv (16)
t(15;17)

80
Q

What are the high risk genetic risk profiles in AML?

A

complex (>5 abnormalities), -5, -7, del(5q), 3q abnormal

81
Q

What is APL? What is the defining clinical clue, the genetic defect and the indicated treatement even before confirmation testing?

A 
Acute promyelocytic leukemia
DIC
t(15;17)
All-trans retinoic acid (ATRA)
Sometimes in combination with chemotherapy, or more recently, ATO (arsenic trioxide)
82
Q

What syndrome can develop from ATRA and ATO? What is the treatment?

A

Differentiation syndrome -> characterized by hypoxemia, pulmonary infiltrates and fever
Stop meds and give steroids

83
Q

What is the indicated treatment for non-APL AML?

A

7 day course of cytarabine and 3 day course of anthracycline

Less toxic regimen is azacitidine or decitabine

84
Q

What is the main difference in presentation in patients with ALL compared to patients with AML?

A

frequent involvement of the CNS requires staging by CSF and prophylaxis with intrathecal chemotherapy

85
Q

How is ALL defined?

A

25% lymphoblasts in the blood or bone marrow

86
Q

What are the biochemical test features of ALL?

A

terminal deoxynucleotidyl transferase positive and

myeloperoxidase negative

87
Q

What are predictors of poor outcome in ALL?

A 
Advanced age
B cell vs T cell disease
> 30K blasts at diagnosis 
Poor risk cytogenetics
the philadelphia chromosome t(9;22)
88
Q

What drug is indicated in Philadelphia positive ALL?

A

Tyrosine kinase inhibitor dasatinib

89
Q

What are the 2 recombinant growth factors used in common clinical practice?

A

G-CSF - to stimulate production of neutrophils in autoimmune neutropenia to hasten neutrophil recovery after cytotoxic chemo and for HSC mobilization.
Recombinant erythropoietin - ACD in CKD patients if iron, B12 and folate levels replete

90
Q

What are the targets before treatment for ESA in CKD?

A

transferrin sat > 20% and serum ferritin > 100

Heme/Onc (9 decks)

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