Sect 7 - ALL, CLL, PLL, HCL

Acute Lymphoblastic Leukemia

What does ALL stand for?

Chronic Lymphocytic Leukemia

What does CLL stand for?

Prolymphocytic Leukemia

What does PLL stand for?

Hairy Cell Luekemia

What does HCL stand for?

T-cell: CD3, CD4, CD8

B-cell: CD19, D20, CD23, CD5

What CD marker can be used to differentiate T cells and B cell leukemias

ALL: children

CLL: adults (median age is 70)

What age group are ALL and CLL most common in?

ALL

acute leukemia of immature lymphocytic cells that occurs most often in children

clinical features of ALL

malaise, fatigue, pallor, easy bruising

epistaxis

bone tenderness

acute onset, progressive

most common in 2-10 year olds

ALL lab features

increased WBC count (>100,000/ul)

1/3 of pts will have normal/low WBC

neutropenia, thrombocytopenia, and anemia

increased LD/uric acid

fibrinogen levels increased

cytochemical stains

blasts neg with Peroxidase, SBB, and NSE

PAS pos

TdT pos

hypercellular with lymphoblastss

bone marrow of ALL

AML has Auer rods

What cellular inclusion helps to differentiate between AML from ALL?

L1: dark, no cytoplasm

L2: larger with more cytoplasm, prominent nucleoli

L3: "starry sky", lots of vacuolization

Differentiate ALL-L1, L2, and L3.

ALL-L1

Clumps of cells

Clefting of cells

NO cytoplasm

ALL-L2

Larger with more cytoplasm

Prominent nucleoli

Vacuolization

Look like receive lymphs & monos

ALL-L3

"Starry Sky" - A LOT of vacuolization

Related to Burkitt's Lymphoma (B-cell lymphoma)

immunological types of ALL

Pro-B (early precursor)

Intermediate Pre-B (common ALL)

Pre-B cell ALL

Burkitt type (B-cell ALL)

Precursor T (T-cell ALL)

Natural Killer cell ALL

1. Remission Induction

2. CNS directed therapy

3. Consolidation

4. Continuation

4 phases of ALL treatment

CLL

malignant monoclonal proliferation of mature B lymphs

- immunologically incompetent

- disease blocks further development of B-cells

- median age 70 years

- men more affected (2:1)

causes of CLL

genetic factors

chromosome add/del (trisomy 12, del 13q, 16q, 11q)

immune imcompentency

clinical features of CLL

fatigue, reduced tolerance to exercise

lymphadenopathy, splenomegaly

persistent infection

easy bruising

pallor

increased bone tenderness

CLL lab features

neutropenia

thrombocytopenia

absolute lymphocytosis (10,000-150,000/ul) (mature)

fragile lymphocytes (smudge cells)

increased uric acid

fragile lymphocytes (smudge cells)

What cells are characteristic of CLL?

albumin

How do we correct smudge cells in CLL?

CD5, 19, 20, 23

CD markers of CLL

**hint: mature B cell lymphs

hypogammaglobulinemia

protein electrophoresis of CLL

stage 1

CLL Stages

lymphocytosis without anemia and thrombocytopenia

less than 3 areas of lymphoid involvement

stage 2

CLL Stages

lymphocytosis without anemia and thrombocytopenia

greater than 3 areas of lymphoid involvement

stage 3

CLL Stages

lymphocytosis with anemia and thrombocytosis

greater than 3 lymphoid involvement

- around 3% of CLL pts develop Richter's transformation (aggressive B-cell lymphoma)

treatment of CLL

control WBC count

reduce symptoms

corticosteroids

most pts are not treated initially

PLL

rare but very aggressive leukemia

- can have either mature B or T cell phenotype

- most cases are de novo, but some arise from CLL

clinical features of PLL

marked splenomegaly

minimal lymphadenopathy

frequent lymphadenopathy, hepatomegaly & skin lesion

7.5 months

median survival for PLL

PLL lab features

extremely high WBC count

absolute lymphocytosis (>300,000/ul)

>55% prolymphocytes

CD20 and 22+

FMC-7+

CD markers for B-cell PLL

CD2, 3, 4, 5+

CD marker for T-cell PLL

HCL

Leukemic Reticuloendotheliosis

- uncommon disorder

clinical features of HCL

disease of middle-aged men

malaise and fatigue

massive splenomegaly

HCL lab features

pancytopenia

bone marrow shows fibrotic replacement (dry tap)

CD19, 20, 22, and 11c

CD marker of HCL, mature B-cells

Tdt (terminal deoxynucleotidyl transferase)

stain that stains DNA polymerase

- stains lymphocytes (fluorescent)

- does not stain Burkitt's lymphoma

TRAP stain

all cells will stain positive for acid phosphatase

BUT only Hairy cell lymphs are resistant to tartaric acid and will remain positive

treatment for HCL

splenectomy

chemo with Cladribine (2-chlorodeoxyadenosine, Leustatin)

CLL: 10,000-150,000 /uL

PLL: >300,000 /uL

Differentiate between CLL and PLL in terms of WBC count

uric acid and Lactate Dehydrogenase (LD)

What two chemistry tests would you expect to be increased when cell proliferation increases?

B-cell leukemia

Is CLL a B-cell or T-cell leukemia?

determines the severity of the disease; helps with treatment

What is the importance of staging in terms of diagnosis?

Myeloblast

Myeloblast OR Lymphoblast

Larger, irregular/lobulated appearance

Positive for: Myeloperoxidase, Sudan Black B, and Specific Esterase

Lymphoblast

More uniform but still big

Positive for PAS