(F) L2.2: Acute lymphoblastic leukemia - primary myelofibrosis Flashcards
(76 cards)
1
Q
- 25% are childhood cancers, 75% of childhood leukemias
- 85% are B-ALL, typically manifests as childhood acute leukemias
- T-ALL mostly presence in adolescent males as thymic lymphoma
- Infiltration of malignant cells into the meninges, testes, and ovaries
Clinical presentation:
* anemia, fever, mucocutaneous bleeding
* lymphadenopathy, with lymph node enlargement
* hepatosplenomegaly
* bone pain
* petechiae (or other evidence of hemorrhage)
A
Acute lymphoblastic leukemia
2
Q
ALL matching type
a. children
b. adults
- poor outlook
- 95% remission, 80% cure rate
- good prognosis
- 80-90% remission, 40% cure rate
A
BAAB
3
Q
What are the most reliable indicators of cellorigin
A
immunotyping and genetic analysis
4
Q
T cell vs B cell matching type
General markers
1. CD19, CD20, CD22, CD24, CD79a, CD10, cytoplasmic u-PAX-5
2. CD2, CD4, CD5, CD8, CD3, CD1a
A
- B cell
- T cell
5
Q
stages of B cell ALL matching type
a. Pro-B , Pre-pre B ALL
b.intermediate B-ALL
c. Pre-B-ALL
- cytoplasmic u
- 5% in children, 11 in adults
- CD10 (cALLa)
- 65% in children, 51% in adults
- 15% in children, 10% in adults
- CD19, cytoplasmic CD79a, cytoplasmic CD22, nuclear TdT
A
- C
- A
- B
- B
- C
- A
6
Q
what are the differential of ALL and AML
A
- morphological
- immunophenotyping
- cytochemical
- cytogenetics
- molecular criteria
7
Q
FAB classification of ALL
- small blasts
- indistinct nuclear shape
- scant nucleoli
- invisible cytoplasm
- single nucleolus
- chromatin is slightly reticulated with perinucleolar clumping
A
L1
8
Q
FAB classification of ALL
- large blasts
- regular oval to round nuclear shape
- prominent, basophilic nucleoli
- prominent cytoplasm with vacuoles
- two to five nucleoli
- chromatin is coarse with clear parachromatin
A
L3
9
Q
FAB classification ofALL
- large, neterogenous blasts
- indented, prominent nuclear shape
- large and abundant nucleoli
- moderately clefted cytoplasm
- single to several indistinct nucleolli
- fine chromatin
A
L2
10
Q
FAB classification of ALL matching type
a. L1
b. L2
c. L3
- Lymphoblastic
- acute lymphoblastic
- Burkitt-type
A
BAC
11
Q
FAB classificaltion of ALL
- most common type of ALL in children
- nucleus is regular with occasional cleft
- nucleoli is prominent and cytoplasm is scant
A
ALL1
12
Q
FAB Classification of ALL
- seen in adults
- cells are large; varying in size
- nucleus is regular with variable basophilia
A
ALL2
13
Q
FAB classification of ALL
- rare form
- can occur in both children and adults
- cells are large with abundant, intensely basophilic cytoplasm
- prominent cytoplasmic vacuolation
- prominent nucleoli
A
L3
14
Q
AML vs ALL
Peroxidase: +
SBB: +
Naphtol A-SDChloroacetateesterase: +
PAS: - or diffusely +
Tdt: -
A
AML
15
Q
AML vs ALL
Peroxidase: -
SBB: -
Naphtol A-SDChloroacetateesterase: -
PAS: + (Coarsegranular or block-like)
Tdt: +
A
ALL
16
Q
Myeloproliferative neoplasm
What are the 5 catergories of MPNs by WHO
A
- Chronic myeloid leukemia (CML)
- Polycythemia vera (PV)
- Essential (primary) thrombocytopenia
- primary myelofibrosis (PMF)
- Other MPNs
17
Q
myeloproliferative neoplasm
what are the other MPNs not included in the main classification done by WHO
A
- chronic neutrophilic leukemia
- chronic eosinophilic leukemia
- not otherwise specified (CEL-NOS)
- MPN unclassified (MPN-U)
18
Q
Myeloproliferative leukemia
which MPNs are genetically related to Jak2+ and Ph(-)
A
polycythemia vera
essential thrombocytopenia
primary myelofibrosis
19
Q
MPNs common features
- cytogenic abnormalities
- (overproduction/underproduction) of one or more types of blood cells with dominance of a transformed clone
- (Hyper/Hypo)cellular marrow or marrow fibrosis
- thrombotic and or hemorrhagic bleeding
- (Extra/intra)medullary hematopoiesis
- Transformation to acute leukemia
A
overpoduction
Hyper
Extramedullary
20
Q
MPNs
what are the treatment for myeloproliferative anemia (2)
A
- molecular therapy
- interferon therapy
21
Q
MPNs
- 20% of leukemias
- clonal proliferative disorder w/c originates from a single abnormal HSC involving ALL hematopietic cell line
- characterized by t(9:22) - Philadelphia chromosome
- Predominant in ages 46-53 years old
Signs and symptoms
1. fatigue
2. decreased tolerance of exertion
3. anorexia
4. abdominal discomfort
5. weight loss
6. symptomatic effects from splenic enlargement
A
chronic myelogenous leukemia
22
Q
what is t(9:22)
A
Philadelphia chromosome
23
Q
left upper quadrant pani is due to ?
A
sign of splenomegaly
24
Q
3 phases of chronic myelogenous leukemia
- 3-4 years
- highly treatable
A
initial (chronic) phase)
25
# 3 phases of chronic myelogenous leukemia
* 6-18 months
* resistance (to treatment) develops
accelerated phase
26
# 3 phases of chronic myelogenous leukemia
* 3-4 months
* generally unresponsive (to treatment)
blast crisis (Acute)
27
# aMPNs
what are the samples used to diagnose chronic myelogenous leukemia
peripheral blood and bone marrow
28
# MPNs
what are the test results indicative of chronic myelogenous leukemia
* hypercellular
* (+) pseudo-Gaucher cells
* molecular techniques
* LAP
29
what is the treatment for chronic myelogenous leukemia
* chemotherapy
* IFN-a; allogenic stem cell transplantation
30
the hematopoietic stem cell of CML contains t(9;22)(q34;q11) resulting in ?
Philadelphia chromosome
31
refers to the shortened chromosome 22
philadelphia chromosome
32
* has tyrosine kinase activity that regulates cell growth
* deregulation results in uncontrolled activity and deregulatioin ocellular proliferation -> decreased apoptosis -> cancer cells will proliferate in the bone marrow and peripheral blood -> increased leukemic cells
BCR / ABL gene
33
what are the three types of the BCR/ABL gene
BCR 1
BCR 2
BCR 3
34
* Best single agent for newly diagnosed patients w CML
* Oral drug
* Introduced in 1998 but was FDA approved on May 10 2001
* Rationale: target the CML positive cells with philadelphia chromosomes
* Resistance is rare in Initial/Chronic phase patients but majority in hthe advanced phase is resistant to imatinib
* If there’s an adequate response and no donor yet = continue the treatment with this until you find donor so you can proceed with allogenic stem transplantation
* If inadequate response = allogenic stem cell transplantation
* If no donor = increase the dose combined with other conventional therapy
IMATINIB mesylate
35
* Presence in CML
* Responsible for the accumulation of lipids
* Presence is important morphological feature of CML
* Crumpled tissue appearance
* a macrophage
Pseudo-Gaucher Cell
36
Caused by chromosomal rearrangements leading to activation of tyrosine kinases (TKs).
CML and Ph+ ALL
37
Effective for Ph+ leukemias, but resistance can develop due to BCR-ABL mutations
Imatinib
38
# CML matchingtype
Median survival:
a. ~1 year
b.~3-4 years
c. <6 months
1. with Ph1
2. without Ph1
3. blast crisis phase
BAC
39
# CML
Treatment, often used after imatinib, with high survival rates in chronic-phase patients.
stem cell transplantation
40
# CML
Can induce hematological remission in early, chronic-phase CML, sometimes combined with cytarabine.
Interpheron alpha
41
# CML
All but one is a prognostic factor for transplantation
* donor type
* donor's age
* disease stage
* gender match
* time from diagnosis to transplantation
donor's age
- it should be RECIEPIENT'S age
42
# common morphologic changes in CML
(decreased / normal/ increased)
**peripheral blood**
1. erythrocytse
2. reticulocytes
3. nucleated red blood cells
4. total white blood cells
5. lymphocytes
6. neutrophils
7. basophils
8. eosinophils
9. myelocytes
10. leukocyte alkaline phosphatase
11. platelets
1. normal or decreased
2. normal
3. present
4. increased
5. normal or increased
6. increased
7. increased
8. increased
9. increased
10. decreased
11. normal or increased
42
# common morphologic changes in CML
(decreased / normal/ increased)
**bone marrow**
1. cellularity
2. granulopoiesis
3. erythropoiesis
4. megakaryopoiesis
5. reticulin
1. increased
2. increased
3. decreased
4. increased or normal
5. increased
43
# common morphologic changes in CML
(sea blue/decreased/ increased)
**macrophages**
1. Gaucher-like
2. Green-gray crystals
1. sea blue
2. increased
44
# common morphologic changes in CML
**megakaryocytes**
1. small
increased
45
# common morphologic changes in CML
(decreased / normal/ increased/ present)
**Extramedullary tissues**
1. splenomegaly
2. sinuspidal
3. medullary
4. hepatomegaly
5. sinusoidal
6. portal tract
7. local infiltrates
present lahat
46
* Characterized by engorged veins, plethora, and elevated red blood cell count.
* Leukocytosis and thrombocythemia are additional features.
* Clonal stem cell disorder.
* Hyperproliferation of erythroid, myeloid, and megakaryocytic lineages.
* Two distinct phenotypes due to gene profiling and cytokine mapping.
* PRV-1, a novel hematopoietic receptor, is highly expressed in normal bone marrow.
* Incidence: 2.3 per 100,000 people.
* Median age at diagnosis: ~60 years.
* Slight male predominance.
* Risk factors: Exposure to radiation, benzene, and petroleum refineries.
Polycythemia vera
47
# PRV
Hallmark of PRV
Plethora
48
# PRV
Which one is not a sign and symptom of PRV
a. Plethora
b. splenomegaly
c. hypotension
d.hypervolmia
c. hypotension, should be hypertension
49
# Diagnostic criteria for PRV
Major or minor criteria
1. endogenous erythroid colony formation
2. hypercellular bone marrow
3. JAK2 mutation
4. low serum erythropoietin levels
5. high hemoglobin
1. minor
2. minor
3. major
4. minor
5. major
50
# Major criteria for PRV
HIGH hemoglobin
a. 18.5 g/dL
b. 16.5 g/dL
1. males
2. females
AB
51
# association type
Treatment for PRV
a. phlebotomy
b. chemotherapy
both
52
* A condition characterized by a significant increase in circulating platelets, usually over 1,000 × 109/L.
* Can be a primary bone marrow disorder or a reactive phenomenon secondary to other conditions.
* Also known as primary thrombocytosis, idiopathic thrombocytosis, and hemorrhagic thrombocythaemia.
* A clonal myeloproliferative neoplasm (MPN) characterized by increased megakaryopoiesis (production of megakaryocytes) and thrombocytosis (high platelet count).
Essential Trombocythemia
53
# Essential trombocythemia
all of the following are major criteria for essential trombocythemia except
a. hyperplasia of megakaryocytes in the bone marrow
b. not meeting criteria for other MPNs
c. presence of a clonal marker
d. presence of JAK2V617F
C
minor criteria
54
* Least common MPN.
* Most frequently occurs in people in their 50s and 60s.
* Affects men and women equally
essential trobocythemia
55
* Originates from multipotential cells and is part of the MPNs, including PRV, CML, and PMF.
* Involves mucocutaneous hemorrhagic diathesis (bleeding tendency) and thromboembolic events (blood clots).
* Both high platelet counts (thrombocytosis) and platelet dysfunction can cause these symptoms.
* Qualitative platelet abnormalities are believed to be the main cause of thromboembolic events.
clonal disorder
56
# essential trobocythemia
T or F
this may have a benign for in patients aged 15-25 years old
T
57
# Association type
clonal disorders with low-grade hyperproliferation of two stem cell lines and significant stimulation of a third
a. PRV
b. essential trombocythemia
c
58
# association type
essential trobocythemia
a. can transform into myelofibrosis
b. can transform to acute leukemia
c.
both essential trombocythemia and PRV can transform to myelofibrosis or acute leukemia
59
how are PRV and essential trombocythemia differentiated?
absence of an expanded RBC (in trombocythemia)
60
# essential trombocythemia
Treatment
a. Therapeutic hemapheresis
b. Alkylating agents and Radioactive Phosphorous (32P)
c. Anagrelide
d. a and b
D
61
* a type of myelofibrosis, which includes primary myelofibrosis, postessential thrombocythemia (ET), and postpolycythemia vera (PPF-MF).
* Characterized by fibrosis (scarring) of the bone marrow and blood cell production outside the bone marrow (extramedullary hematopoiesis).
* Causes:
Secondary myelofibrosis can be caused by other diseases, infections, or exposure to chemicals and radiation.
primary myelofibrosis (PMF)
62
What type of disorder is Primary Myelofibrosis (PMF)?
A. Lymphoid disorder
B. Clonal disorder
C. Infectious disorder
D. Autoimmune disorder
B. Clonal disorder
63
What happens early in PMF regarding the blood-marrow barrier?
A. It becomes more rigid
B. It is disrupted, allowing immature cells into the bloodstream
C. It strengthens to protect the bone marrow
D. It disappears completely
B. It is disrupted, allowing immature cells into the bloodstream
64
What percentage of PMF patients develop bone sclerosis?
A. None
B. half
C. All patients
D. 25%
B. half
65
What causes myelofibrosis in PMF?
A. Direct clonal proliferation of fibroblasts
B. Reaction to abnormal hematopoietic cells
C. Infection in the bone marrow
D. Overactivation of osteoblasts
B. Reaction to abnormal hematopoietic cells
66
What abnormalities are observed in megakaryocytes in PMF?
A. Giant forms and micromegakaryocytes
B. Lack of nucleus
C. Only giant forms
D. Only micromegakaryocytes
Answer: A. Giant forms and micromegakaryocytes
A. Giant forms and micromegakaryocytes (+ naked nuclei)
67
Where does extramedullary hematopoiesis commonly occur in PMF?
A. Liver
B. Spleen
C. Brain
D. Lymph nodes
B. Spleen
68
Which growth factors are involved in the development of myelofibrosis?
A. Erythropoietin and insulin-like growth factor
B. Platelet-derived growth factor (PDGF) and PF4
C. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)
D. Tumor necrosis factor (TNF) and interleukin-6 (IL-6)
B. Platelet-derived growth factor (PDGF) and PF4
69
What type of cells increase in the hematopoietic microenvironment in PMF?
A. Transitional reticular cells and myofibroblasts
B. Osteoblasts and osteoclasts
C. Lymphocytes and macrophages
D. Adipocytes and endothelial cells
A. Transitional reticular cells and myofibroblasts
70
# primary myelofibrosis
Prognostic scoring system
a. 69 months survival
b. 33 months survival
c. 4 months survival
1. intermediate risk group
2. high-risk group
3. low-risk group
BCA
71
# association type
rare presentation for primary myelofibrois
a. breast mass
b. skin lesions with two types of blood cells
a
(skin lesions with **three** types of blood cells: myeloid, erythroid, and megakaryocytic)
72
# primary myelofibrosis
longer or shorter survival rate?
hgb level >10g/dL
platelet counts >100 x10^9 g/dL
osteomyelosclerosis
longer survival rate
*shorter if less than the values above and without osteomyelosclerosis
72
73
# primary myelofibrosis
Disease phases
a. 29% blast cells, poor prognosis
b. <10% blast cells in blood or bone marrow
c. 10-19% blast cells
1. Accelerated phase
2. Chronic phase
3. Blast phase
CBA
74
# Pimary myelofibrosis treatment association type
blood transfusion
a. symptomatic
b. asymptomatic
a
*asymptomatic patients do not require treatment
