MATURE LYMPHOCYTIC LEUKEMIAS

Question 1

: Mainly affects the blood and bone marrow

Answer 1

CLL

Question 2

: Primarily involves the lymph nodes and spleen

Answer 2

SLL

Question 3

Most common leukemia in adults (median age: 69 years)

Answer 3

CLL/ SLL

Question 4

• B-cell malignancy
• Male predominance (M>F)

Answer 4

CLL/ SLL

Question 5

• Can be asymptomatic and incidentally diagnosed on routine blood tests

Answer 5

CLL/SLL

Question 6

CLL/SLL

IWCLL criteria: sustained presence of at least______circulating B lymphocytes with documentation of clonality by flow cytometry

Answer 6

5 × 10^9/L

Question 7

CLL/ SLL median age

Answer 7

69

Question 8

Morphology
• Small and mature cells with minimal cytoplasm and a dense nucleus with condensed chromatin pattern and inconspicuous nucleolus

Answer 8

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Question 9

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• Chromatin pattern:
“_______”
• Nucleus: (3)

Answer 9

cobblestone

“soccer ball”, “pepperoni pizza”, “cracked earth”

Question 10

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• Prolymphocytic progression of
CLL/SLL
• Prolymphocytes______% in BM or
PBS
- More aggressive disease

Answer 10

> 15%

Question 11

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• Fragile CLL lymphocytes damaged during PBS prep
- Counted as lymphocytes

> 30% = better prognosis

Answer 11

• Smudge cells

Question 12

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
_______
CD19, CD20, CD23
_______
• T cell antigen

Answer 12

• B cell markers

• CD5+

Question 13

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Catovsky-Matutes Scoring for Chronic Lymphocytic Leukemia Diagnosis

Score 1 point for each of following:
Weak expression of surface immunoglobulin
Expression of CD5
Expression of CD23
No expression of FMC7
Absent or weak expression of CD79b or CD22

A combined score of_______ is consistent with a diagnosis of CLL, whereas a lower score is suggestive of some other lymphoid neoplasm.

Answer 13

4 or greater

Question 14

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Staging and Prognosis
(2)

Answer 14

Rai Classification
Binet Classification

Question 15

• Risk categories reflecting the degree of organomegaly/ lymphadenopathy or compromise of marrow function

Answer 15

Rai Classification, Binet Classification

Question 16

Low Risk (formerly Stage 0)
Lymphocytosis >5 × 10^9L

Intermediate Risk (formerly
Stages I and lI)
Lymphocytes >5 × 10^9/L and
(lymphadenopathy + splenomegaly) or hepatomegaly, or both

High Risk (formerly Stages Ill and IV)
Lymphocytes >5 × 10%/L and hemoglobin <11 g/dL or platelets <100 × 10^9/L

Answer 16

Rai Classification (Revised)

Question 17

Rai Classification

Low Risk (formerly Stage 0)
Lymphocytosis_____

Intermediate Risk (formerly
Stages I and lI)
Lymphocytes______

High Risk (formerly Stages Ill and IV)
Lymphocytes______

Answer 17

> 5 × 10^9L

> 5 × 10^9/L and
(lymphadenopathy + splenomegaly) or hepatomegaly, or both

> 5 × 10%/L and hemoglobin <11 g/dL or platelets <100 × 10^9/L

Question 18

Stage A
Hemoglobin ≥10 g/dL and platelets ≥100 × 10ª/L and <3 enlarged nodal areas

Stage B
Hemoglobin ≥ 10 g/dL and platelets ≥100 × 10°/L and ≥3 enlarged nodal areas

Stage C
Hemoglobin <10 g/dL or platelets <100 × 109/L and any number of enlarged nodal areas

Answer 18

Binet Classification

Question 19

Binet Classification

Stage A
Hemoglobin _____and platelets_____ and_____ enlarged nodal areas

Stage B
Hemoglobin_____ and platelets_____ and_____ enlarged nodal areas

Stage C
Hemoglobin_____ or platelets_____ and____ of enlarged nodal areas

Answer 19

A: ≥10 g/dL ; ≥100 × 10^9/L; <3

B: ≥ 10 g/dL ; ≥100 × 10^9/L; ≥3

C: <10 g/dL; <100 × 10^9/L; any number

Question 20

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Treatment
• Alkylating agents (chlorambucil, cyclophosphamide)
• Nucleoside analogues (fludarabine)
• Anti-CD20 antibody (rituximab)
• BT inhibitors (ibrutinib, acalabrutinib)
• PI3k inhibitors (idelalisib)
• BCL2 inhibitors (venetoclax)

Question 21

• Documented monoclonal B-cell population but with <5 × 10%/L circulating B lymphocytes

Answer 21

LYMPHOCYTIC LEUKEMIAS
Monoclonal B-Cell Lymphocytosis (MBL)

Question 22

Features:
• Asymptomatic
• Without lymphadenopathy, organomegaly, cytopenias or systemic symptoms

Answer 22

LYMPHOCYTIC LEUKEMIAS
Monoclonal B-Cell Lymphocytosis (MBL)

Question 23

MBL

Risk of progression to CLL:

Answer 23

1-2% per year

Question 24

: <5 x 10%/L circulating monoclonal B lymphocytes but with evidence of disease (adenopathy/organomegaly)

Answer 24

SLL

Question 25

: >5 x 10%/L circulating monoclonal B lymphocytes but ***with evidence of disease (adenopathy/organomegaly)***

Answer 25

- CLL

Question 26

: <5 x 10%/L circulating monoclonal B lymphocytes but ***with evidence of disease (adenopathy/organomegaly)***

Answer 26

- SLL

Question 27

: <5 x 10%L circulating monoclonal B lymphocytes ***without evidence of disease (lymphadenopathy, organomegaly, cytopenias or systemic symptoms)***

Answer 27

MBL

Question 28

• 2% of mature lymphoid leukemias • Disease of the elderly (median: 65 years) • Male = female • Aggressive disorder

Answer 28

T-Prolymphocytic Leukemia (T-PLL)

Question 29

Clinical Manifestations: • Massive splenomegaly • WBC >100 x10^9/L with prolymphocyte predominance • Minimal lymphadenopathy • Skin infiltration

Answer 29

T-Prolymphocytic Leukemia (T-PLL)

Question 30

LYMPHOCYTIC LEUKEMIAS T-Prolymphocytic Leukemia (T-PLL) •_____ of mature lymphoid leukemias • Disease of the elderly (median: ____years) •______ • Aggressive disorder

Answer 30

2% 65 Male = female

Question 31

LYMPHOCYTIC LEUKEMIAS T-Prolymphocytic Leukemia (T-PLL) Clinical Manifestations: • Massive_____ • WBC _______/L with prolymphocyte predominance • Minimal_____ •_____ infiltration

Answer 31

splenomegaly >100 x10^9/L lymphadenopathy Skin

Question 32

T-Prolymphocytic Leukemia (T-PLL) - Previously: PLL is subclassified as (2)

Answer 32

B-cell PLL or T-cell PLL

Question 33

• MCL (+) for IGH::CCND1 fusion gene or • CLL/SLL with prolymphocytic progression or • Splenic B-cell lymphoma/leukemia with prominent nucleoli

Answer 33

B-cell PLL (B-PLL)

Question 34

Laboratory Findings - ***Cytoplasmic protrusions/blebbing of T prolymphocytes***

Answer 34

T-Prolymphocytic Leukemia (T-PLL)

Question 35

• CD7+, TCL-1+ • Inv(14) (80%)

Answer 35

T PLL

Question 36

T-Prolymphocytic Leukemia (T-PLL) Treatment •__________ • Standard of care • Complete response in 90% -_______ • Remission in 20-30%

Answer 36

Anti-CD52 Ab (Alemtuzumab) HSCT

Question 37

• Indolent disease of B-cell lineage

Answer 37

Hairy Cell Leukemia

Question 38

Hairy Cell Leukemia • Middle aged individuals (median:____ years) - Primarily involves (3) - Features: (2)

Answer 38

50 spleen, blood, BM splenomegaly and cytopenias

Question 39

Laboratory Findings • Hairy B cells

Answer 39

Hairy Cell Leukemia

Question 40

• Ovoid or kidney-bean shaped nuclei without nucleoli and abundant blue-gray cytoplasm with ragged, hairlike projections extending circumferentially

Answer 40

• Hairy B cells

Question 41

• BMA: ***dry tap*** • Anti-CD20+ • Annexin A: specific to HCL

Answer 41

Hairy Cell Leukemia

Question 42

Hairy Cell Leukemia Treatment

Answer 42

• Splenectomy • Purine analogues (Cladribine/2-CDA, pentostatin) - BRAF inhibitors (vemurafenib)

Question 43

Leukemia Laboratory Findings • Large Granular Lymphocytes • Abundant ***pale blue cytoplasm with medium to large azurophilic granules***

Answer 43

Large Granular Lymphocytic (LGL)

Question 44

Large Granular Lymphocytic (LGL) Leukemia Laboratory Findings • ____of circulating lymphocytes or_____ in healthy adults - Counted with normal lymphocytes

Answer 44

15% <0.6 ×10^9/L

Question 45

• >2 x10^9/L circulating LGLs persistent for more than 6 mos in the absence of any associated condition - Disease of older adults (median: 60 years) • Asymptomatic

Answer 45

Large Granular Lymphocytic (LGL) Leukemia

Question 46

Large Granular Lymphocytic (LGL) Leukemia Median age

Answer 46

60 years

Question 47

Large Granular Lymphocytic (LGL) Leukemia Diagnosis ________ - Clonal expansion of cytotoxic T cells - CD3+, CD8+, CD57+ • (+) TCR gene rearrangement

Answer 47

• T-large Granular Lymphocytic Leukemia

Question 48

Large Granular Lymphocytic (LGL) Leukemia Diagnosis _________ • Clonal expansion of NK cells • CD3- • CD56+ • Restricted KIR expression

Answer 48

NK-large Granular Lymphocytic Leukemia

Question 49

Large Granular Lymphocytic (LGL) Leukemia Treatment

Answer 49

- Myeloid growth factors - Immunosuppressive agents (MTX, cyclophosphamide, cycloporin A)