Lymphoid Leukemia Application

Question 1

What does this patient have?
What demographic?
Normal/abberant immunophenotype?
Poly/monoclonal?
Symptoms?

Answer 1

Mononucleosis
Teenager
Normal
Polyclonal
Fatigue, pharyngitis, splenohepatomegaly

Question 2

What does this patient have?
What demographics?
Normal/abberant immunophenotype?
Poly/monoclonal?

Answer 2

CLL
Elderly
Abnormal
Monoclonal

Question 3

What is absolute lymphocytosis?
What is the difference between reactive or neoplastic? (Duration, Morphology, Absolute Count, Associated Clinical Findings, Flow cytometery)

Answer 3

>4,000/microL of lymphocytes
Reactive - Acute Duration, Heterogenous, 10-12K or less, Flow reveals polyclonal
Neoplastic - Chronic Duration, Homogenous (Monotonous), 20-40K, Flow reveals monoclonal

Clinical findings are actually pretty common, specific things such as excessive fatigue and weight loss push towards neoplastic

Question 4

What other viruses/pathogens cause mono-like syndromes?

Answer 4

CMV, Adeno, Acute HIV, Toxo

Question 5

How do we assess B cells for clonality?

Answer 5

Light chain restriction on cell surface (kappa v lambda) via flow or immunohistochem
IgH variable gene PCR - One (mono) vs multiple (poly) rearrangements
Immunophenotypic aberrancy (e.g. CD5 (T-cell marker) expression on B cells)

Question 6

T/NK assessment for clonality?

Answer 6

TCR gene PCR
Immunophenotypic aberrancy

Question 7

Flow assessment for clonality? What’s left vs right?

Answer 7

Left - Polyclonal
Right - Monoclonal

Question 8

What is this cell indicative of disease?
What kind of cell is this?
What would be the next step to characterize these cells?

Answer 8

ALL
Immature cell (Lymphoblast)
Flow cytometery (determine clonality and lineage)

Question 9

What is a smudge cell count used for?
Is it specific?

Answer 9

Determine CLL
No, also occurs with mono, but it is classically tested

Question 10

What markers are indivative for B-ALL?

Answer 10

CD10+/CD19+ (B-cell specific)/CD34+ (Blast specific))
CD3- (T-cell)/CD20- (Mature B-cell)

Question 11

Where can B-ALL expand to?

Answer 11

CSF
Lymph nodes
Bone marrow
Splenic sinusoids

Question 12

Is hypocellularity a finding with ALL?

Answer 12

Not in bone marrow (hypercellulairty in bone marrow)
Cytopenias would appear in peripheral blood

Question 13

What are good prognostic genetics for B-ALL?
What are bad prognostic genetics?
Where are the karyotypes taken from?

Answer 13

Good: Hyperdiploidy, t(12;21)

Bad: Hypodiploidy, t(9;22),11q23 abnormalities (MLL)

They are taken from the specific aberrant cells, can be compared to a buccal swab which should find normal karyotypes

Question 14

What is a large mediastinal mass from an adolescent male indicates?
What would be a charactersitic immunophenotypic finding of this tumor?

Answer 14

T-ALL
CD3+ phenotype

Question 15

Ratio of B-ALL vs T-ALL

Answer 15

85% to 15%

Question 16

Definition of acute leukemia
Can it involve extramedullary sites?
What are the two big categories and the morphology/immunophenotype?

Answer 16

>20% blasts in the blood or bone marrow
Yes

Myeloid - CD13,14,15,33,117 w/w/o Auer rods
Lymphoid - CD3,CD19,CD20

Question 17

What is the pre-leukemic state of AML?
What are the classification states of AML?

Answer 17

Myelodysplasia - Pre-leukemia
AML w/recurrent cytogenic abnormalities
AML w/myelodysplasia-associated changes
AML/MDS, therapy-related
AML, NOS

Question 18

Prognostic factors in B-ALL

Answer 18

Age (2-10 is good, otherwise bad)
Cytogenetic
Elevated WBC count is poor (>100K/uL)
CSF involvement is poor
Marrow involvement at day 15 is poor

Question 19

Treatment of ALL (stages)

Answer 19

Induction - Initiate remission
Intensification - Keep up remission
CNS Prophylaxis - Chemo doesn’t enter the brain
Maintenance

Question 20

How is CNS prophylaxis done for ALL?
What other part of the body needs special concern for ALL?

Answer 20

Irradiation or IT methotrexate

Testes also is protected from chemo

Question 21

Cure rate for Adult vs Pediatric ALL

Causes of differences?

Answer 21

Adult - 50%
Pediatric - 80-90%

Differences in disease and resillience of the body to handle the chemo

Question 22

What is so special about bispecific T-cell engaging (BiTE) antibody?

Answer 22

Directs cytotoxic T-cells to CD19 expressing B-cells to kill them
Blinatumonab

Question 23

How is prognosis for Philidelphia ALL?
What drug improves it?

Answer 23

Horribly bad (7%)
Dasatinib raises it up to 40%+

Question 24

What is the characteristic cell description for CLL?
What are the immunophenotype of CLL?

Answer 24

“Soccer ball” or “Ginger-snap”
CD5+/CD19+/CD20+/CD23+ with monoclonality (single light chain)

Question 25

What are the causes of anemia in CLL?

Answer 25

Primarily due to crowding out in bone marrow Secondarily due to immune-mediated destruction of precursors

Question 26

Prognostic Indicators in CLL/SLL

Answer 26

Good: Low Rai stage, Mutated Ig Heavy Variable (IGHV) gene, Deletion 13q Bad: High Rai stage, Unmutated IGHV gene, CD38/ZAP70 expression, Deletion 11q,17p

Question 27

What is the classification criteria for small B cell leukemia/lymphomas with

Answer 27

Question 28

"Natural" prognosis based on stage for CLL/SLL

Answer 28

Stage 0 - 150 months Stage I - 101 months Stage II - 71 months Stages III/IV - 9 Months

Question 29

What are CLL/SLL indications to treat? What do we treat with?

Answer 29

Lab: Rapid lymphocyte doubling time (\< 6 months), Hgb \< 10g/dL (Stage III), Platelets \< 100k/uL Clinical: Autoimmune anemia or thrombocytopenia, richter transformation (large cell transformation), enlaarging symptomatic lymph nodes, B symptoms FCR

Question 30

What are we trying to do with 17p CLL patients?

Answer 30

Target B-cell signaling (specifically Rituximab (PI3 Kinase) with a BTK inhibitor)

Question 31

What diseases have atypical lymphocytes +/- lymphocytosis?

Answer 31

CLL/SLL Leukemic lymphoma (follicular, mantle, etc) Hairy cell leukemia Adult T cell leukemia/lymphoma Sezary

Question 32

Classic presentation of Hairy cell leukemia: Demographics, symptoms, exam finding, immunophenotyping

Answer 32

40-60 y/o males Any symptom associated with pancytopenia Splenomegaly Flow diagnosis: Bright CD11c and CD22 expression; TRAP+

Question 33

What cells are affected by Sezary syndrome? Whats the triad? What is the classical histology? Which skin condition is it affiliated with? Potential prognostic complication?

Answer 33

CD4+ T-cell neoplasm Triad of erythroderma, generalized, lymphadenopathy, circulating sezary cells Cells have "cerebriform nuclei" Related to mycosis fungoides SS/MF may transform to aggressive T-cell tumor

Question 34

What is adult T-cell leukemia/lymphoma associated with cell wise? What virus is it paired with? Place in world associated with? Histological finding? Lab finding? Clinical course?

Answer 34

CD4+ Neoplasm HTLV-1 Associated (Not specific) Japan, Caribbean, Africa Flower cell with lymphocytosis Hypercalcemia Aggressive

Question 35

What cells are associated with large granular lymphoytic leukemia? What is the clinical course? What does it present with? What other diseases is it associated with?

Answer 35

Cytotoxic T cells, NK cells Indolent disorder Neutropenia, anemia, splenomegaly Autoimmune disorders (rheumatoid arthritis)