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Oncology > 4 - Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia > Flashcards

4 - Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia Flashcards

1
Q

ALL

A 
Acute LymphoBLASTic Leukemia
Focuses on very early immature cells
Aggressive
Requires immediate treatment
Curable
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2
Q

CLL

A

Chronic LymphoCYTic Leukemia
Often indolent
May not need treatment for years
Incurable

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3
Q

ALL - Detected but not treated

A

You could die within days to weeks

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4
Q

Malignant lymphocytes mainly in the lymph nodes

A

Lymphoma

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5
Q

Malignant lymphocytes mainly in the blood and bone marrow

A

Leukemia

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6
Q

Lymphocytic Leukemia - Arrested a mature state

A

CLL

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7
Q

Lymphocytic Leukemia - Arrested at an immature state

A

ALL

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8
Q

2 Types of ALL

A

B Cell

T Cell

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9
Q

ALL - Incidence

A

Rare

~1000 cases per year

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10
Q

ALL - Prognosis

A

Pediatrics - Curable, even at relapse

Adults - Often fatal

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11
Q

ALL - Risk Factors

A

Radiation exposure

Trisomy 21

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12
Q

ALL - Patient Presentation

A

Acute complications of cytopenias (Bleeding, Infection, Fatigue, Dyspnea, Dizziness)
Fever
Bone Pain
Rarely lymphadenopathy

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13
Q

Acute complications of cytopenias

A 
Bleeding
Infection
Fatigue
Dyspnea
Dizziness
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14
Q

ALL - Microscopic

A 
Large redundant lymphocytes
Open chromatin
Prominent nucleoli
Light purple cytoplasm
No granules
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15
Q

ALL - Physical Exam

A 
Signs of anemia
Ecchymosis, petechiae
Lymphadenopathy (rare)
Splenomegaly (rare)
Rash (from an infection)
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16
Q

ALL - Diagnosis

A 
Bone Marrow Tests:
Core biopsy
Flow cytometry
Aspirate slides
Cytogenetics

Source for core biopsy: Superior iliac crest (feel through the skin)

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17
Q

Flow Cytometry

A

Critical test for all lymphoid malignancies
Less critical for myeloid malignancies

Suck fluid out of bone marrow, or take blood
Label the cells with fluorescent antibodies
Shoot cells down a channel
Hit them with a laser and see what lights up

Therapeutic implications:
Once you know which surface markers are on a cancer cell, you can target those cells using that surface marker.

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18
Q

B Cell ALL - Diagnosis on Flow Cytometry

A 
TdT
CD19 (can be therapeutic target)
CD22
CD79
Immunoglobulin
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19
Q

T Cell ALL - Diagnosis on Flow Cytometry

A

TdT
CD7
CD2
CD3

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20
Q

CD19

A

B Cell ALL Marker

Can be therapeutic target

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21
Q

T Cell ALLs often present with

A

Large mediastinal mass

When it disappears, it means you’ve given good chemotherapy and it’s worked

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22
Q

Components of Therapy - ALL

A

Induction
CNS Therapy
Intensification
Maintenance

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23
Q

ALL Therapy - Induction

A 
Prednisone
Dexamethasone
Vincristine
Doxorubicin
Cyclophosphamide
Asparaginase
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24
Q

ALL Therapy - CNS Therapy

A

Craniospinal irradiation
Intrathecal Methotrexate and Cytarabine

This is important because ALL spreads to the CNS through the CSF

Maybe don’t radiate kids though if you can avoid it. Check CSF to see if there’s any cancer in there.

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25
Q

ALL Therapy - Intensification

A

Similar to Induction:

Prednisone
Dexamethasone
Vincristine
Doxocubicin
Cyclophosphamide
Asparaginase
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26
Q

ALL Therapy - Maintenance

A

Prednisone
Mercaptopurine
Methotrexate

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27
Q

ALL Therapy - Time Course

A

2+ years

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28
Q

Chemotherapy - Dexamethasone

A

Directly toxic to lymphocytes

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29
Q

Chemotherapy - Prednisone

A

Directly toxic to lymphocytes

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30
Q

Chemotherapy - Vincristine

A

Inhibits microtubule polymerization

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31
Q

Chemotherapy - Doxorubicin

A

Inhibits Topoisomerase II

Used in lymphoma, leukemia, breast cancer, etc

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32
Q

Chemotherapy - Cyclophosphamide

A

Alkylating agent - Induces bulky DNA lesions

33
Q

Chemotherapy - Asparaginase

A

Depletes asparagine
ALL cells are particularly sensitive to this.
Most other tumors are not.

34
Q

Chemotherapy - Methotrexate

A

Folate antagonist

35
Q

Complications of ALL

A

DIC

Tumor Lysis Syndrome

36
Q

DIC Labs

A 
PT ↑
aPTT ↑
Fibrinogen ↓ (sometimes "spuriously" normal)
D-Dimer ↑
Platelets ↓
Schistocytes +/-
37
Q

DIC - Treatment

A

Cryoprecipitate

38
Q

Tumor Lysis Syndrome Labs

A

K+ ↑ (from lysed cells and reduced renal clearance)
Creatinine ↑ (from acute renal failure due to Uric Acid)
Uric Acid ↑ (from DNA breakdown)
Phosphorous ↑ (from lysed cells)
LDH ↑ (from lysed cells)
Calcium ↓ (it binds to phosphorous)

39
Q

How do you prevent the complications of Tumor Lysis Syndrome?

A

Allopurinol (prevent Uric Acid formation)

Rasburicase (break down Uric Acid)

40
Q

Allopurinol

A

Prevents breakdown from xanthine to uric acid

Doesn’t help the problem if the patient already has high levels of uric acid.

41
Q

Rasburicase

A

Recombinant enzyme
Breaks down Uric Acid into Allantoin (white stuff in bird poop)
Costs more than $10,000

42
Q

ALL - Adverse Prognostic Factors

A 
Younger than 1 year old
Older than 10 years old
Adults - Increasing age, especially over 60
WBC > 30K (B-Cell)
WBC > 100K (T-Cell)
Adverse cytogenetics
B-Cell Phenotype
Presence of minimal residual disease
43
Q

Minimal Residual Disease

A

Detect DNA left over from leukemia cells when in apparent remission
Test: PCR
Indicates likelihood of relapse

44
Q

ALL - Adverse Cytogenetic Risk Factors

A

t(9;22) “Philadelphia Chromosome” - Poor Prognostic Marker, more common in adults

t(4;11) “Mixed Lineage Leukemia” - Poor Prognostic Marker, more common in infants

Hyperdiploidy - Favorable Prognostic Marker, more common between ages 1 and 10

45
Q

ALL - Allogeneic Bone Marrow Transplant

A

Young patients with adverse cytogenetics in first remission
Standard treatment for relapsed ALL in young patients

Important factors in other scenarios:
Patient Age
Presence of HLA-matched sibling

46
Q

2 new therapies for ALL

A

Blinatumomab

CART therapy

47
Q

Blinatumomab

A

Bispecific T-Cell engaging Ab (BiTE)
Redirects T cells to lyse CD19+ malignant and nonmalignant B cells

It’s essentially an adaptor, hooking up T Cells and CD19 B Cells

Effective in patients who have not responded well to standard therapy

Costs $200,000

48
Q

CART Cells

A

Chimeric Antigen Receptor T Cells

Take T Cells out of the body, transfect them with DNA that causes them to express a novel T Cell receptor specifically looking for CD19

Effective in getting rid of refractory ALL

They may never make antibodies again, though.

49
Q

CLL - Incidence

A

Most common form of leukemia
Only form of leukemia with NO increased incidence with a-bomb survivors
Disease of the elderly

50
Q

CLL - Microscopic Smear

A

Small redundant lymphocytes (around the size of an RBC)
Clumped chromatin
Absent nucleoli
Light purple cytoplasm
Smudge cells (not pathognomonic, but frequently seen)

51
Q

CLL - Patient Presentation

A

Asymptomatic Lymphocytosis
Lymphadenopathy (Common)
Chronic complications of cytopenias (recurrent sino-pulmonary infections, gradual fatigue, dyspnea, dizziness)
Chronic weight loss

52
Q

Chronic complications of cytopenias

A

Recurrent sino-pulmonary infections

Gradual fatigue, dyspnea, dizziness

53
Q

CLL - Diagnosis on Flow Cytometry

A 
Predominance on lymphocytes of:
CD5
CD19
CD20 (can be therapeutic target)
CD23

Adverse prognosis: High expression of CD38 & ZAP-70

Look for “light chain restriction” meaning only kappa or lambda light chains are expressed, not both (which would indicate normal light chains)

54
Q

CLL Diagnosis

A

No bone marrow needed. Can do flow cytometry on the blood

55
Q

CLL - Cytogenetics order of prognosis (Worst-to-best)

A 
17p Deletion (lose p53)
11q Deletion
12q Trisomy
Normal
13q Deletion as SOLE abnormality
56
Q

CLL - Heavy Chain Hypervariable Region Mutations

A

If you see mutations in the hypervariable region of the heavy chains on surface Ab, it is a FAVORABLE prognosis.
Wild type hypervariable regions indicate POOR prognosis.

57
Q

CLL - Stage 0

A

Monoclonal lymphocytosis

>6,000/μL

58
Q

CLL - Stage 1

A

Lymphadenopathy

59
Q

CLL - Stage 2

A

Hepatosplenomegaly

60
Q

CLL - Stage 3

A

Hemoglobin

61
Q

CLL - Stage 4

A

Platelets

62
Q

If a patient has asymptomatic CLL, when do we treat?

A

At Stage 3!

63
Q

Immune Dysregulation due to CLL

A 
Immune Thrombocytopenic Purpura (ITP)
Autoimmune Hemolytic Anemia (AIHA)
Hypogammaglobulinemia
Pure Red Cell Aplasia (PRCA)
Other auto-immune diseases
64
Q

Venn Diagram of Mechanisms of Thrombocytopenia

A

ITP (platelets low, out of proportion to the hemoglobin)
Splenic sequestration
Marrow involvement

65
Q

CLL - Indications for treatment

A 
Stage 3/4 CLL
Rapid lymphocyte doubling time (faster than every 6 months)
Symptomatic lymphadenopathy
Fevers, night sweats, weight loss
Transformation to high grade lymphoma
66
Q

CLL Treatment - Agents

A 
Cyclophosphamide (C)
Fludarabine (F)
Rituximab (R)
Bendamustine (B)
Alemtuzumab
Ofatumumab
Chrlorambucil
67
Q

CLL Treatment - Regimens

A

FCR:
Fludarabine
Cyclophosphamide
Rituximab

FR:
Fludarabine
Rituximab

BR:
Bendamustine
Rituximab

68
Q

Chemotherapy - Fludarabine

A

Nucleoside Analogue

69
Q

Chemotherapy - Rituximab

A

Monoclonal Ab to CD20

Partially humanized, but synthesized in mouse ovaries
Opsonizes CLL B Cells

70
Q

Chemotherapy - Ofatumumab

A

Monoclonal Ab to CD20

71
Q

Chemotherapy - Obinotuzumab

A

Monoclonal Ab to CD20

72
Q

Chemotherapy - Alemtuzumab

A

Monoclonal Ab to CD52

73
Q

Chemotherapy - Chlorambucil

A

Alyklating agent - Induce bulky DNA lesions

74
Q

Chemotherapy - Bendamustine

A

Aklylating agent - Induce bulky DNA lesions

75
Q

Idelalisib

A

New Therapy for CLL. Blocks PI3kδ
PO therapy

Small molecular inhibitors of growth pathways in CLL cells

B cell receptors aren’t just important in recognizing antigen. They also trigger proliferation. Poison that pathway with these drugs.

76
Q

Ibrutinib

A

New Therapy for CLL. Blocks BTK
PO therapy

Small molecular inhibitors of growth pathways in CLL cells

B cell receptors aren’t just important in recognizing antigen. They also trigger proliferation. Poison that pathway with these drugs.

77
Q

Idelalisib & Ibrutinib

A 
Oral Monotherapy
Highly effective in relapsed CLL
Effective in 17p- Disease
Effective in the infirm
Induce transient lymphocytosis
78
Q

Only cure for CLL

A

Allogeneic Bone Marrow Transplant

Carries a high mortality rate (10 - 40%)

Oncology (23 decks)

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