Chronic Lymphoproliferative Disorders, Plasma Cell Myeloma And Amyloidosis

Question 0

How does one class chronic lymphoproliferative disorders?

Answer 0

Are either B or T cell malignancies.

*some are more leukaemic and some are more lymphomatous.

Question 1

What is the difference between a lymphoma and leukaemia?

Answer 1

Lymphoma- solid lymph node mass.

Leukaemia- circulating cells in peripheral blood.

Question 2

List the types of B Cell chronic leukaemias.

Answer 2

Chronic lymphocytic leukaemia (common)
Hairy cell leukaemia
Prolymphocytic leukaemia
Some typical Non-Hodgkin lymphomas may spill into peripheral blood when advanced

Question 3

Types of chronic T cell leukaemias?

Answer 3

T prolymphocytic leukaemia
Large granular lymphocytic leukaemia
Adult T cell leukaemia/lymphoma

Question 4

Some of the methods used to diagnose chronic leukaemias?

Answer 4

Blood tests - chronic persistent lymphocytosis
Morphology 
Immunophenotype
Cytogenetics
Genetics

Question 5

Who are most at risk with regards to chronic lymphocytic leukaemia (CLL)?

Answer 5

Older age group (60-80)

There is a genetic predisposition

Question 6

What is the problem in chronic lymphocytic leukaemia (CLL)?

Answer 6

Accumulation of monoclonal mature B Lymphocytes in the:

• blood
• bone marrow
• liver
• spleen
• lymph nodes
• is due to reduced apoptosis

Question 7

Clinical features or chronic lymphocytic leukaemia?

Answer 7

Males affected 2:1
Lymph node enlargement --> non-tender, symmetrical 
Anaemia
Thrombocytopenia
Splenomegaly
Immunosuppression

Question 8

Which sex is more affected with regards to chronic lymphocytic leukaemia?

Answer 8

M:F 2:1

Question 9

Lab features of chronic lymphocytic leukaemia?

Answer 9

Lymphocytosis
Normocytic anaemia/autoimmune haemolysis (spherocytes)
Sometimes neutropenia/thrombocytopenia
Decreased serum Ig

Question 10

Features of a peripheral blood smear regarding chronic lymphocytic leukaemia?

Answer 10

WCC - lymphocytosis
Small round lymphocytes
Smear cells (due to fragile B cells)

Question 11

Which staging system is used to stage CLL?

Which end of the scale indicates a poorer prognosis?

Answer 11

Rai staging system.
Rai 0 or 1 - good prognosis.
2-4 associated with more advanced disease.

Question 12

How to treat CLL?

Answer 12

Will partially respond to chemo but more about managing symptoms:

• treat problamatic organomegaly
• bone marrow suppression(anaemia, thrombocytopenia, neutropenia)
• haemolytic episodes

Question 13

Ehat are the aims of treatment with regards to CLL?

Answer 13

Support not cure (cure is rare)

Control symptoms and limit extent of leucocytosis (using chemo).

Question 14

What group of people does one see Hairy Cell Leukaemia in?

Answer 14

More in males of older age (40-60yo).

Is rare!

Question 15

How do people with Hairy Cell Leukaemia present?

Answer 15

Severe infectons.
Anaemia.
Splenomegaly.

Question 16

What does hairy cell leukaemia NOT present with?

Answer 16

Lymphadenopathy.

Question 17

Why is it called hairy cell leukaemia?

Answer 17

Affected B cells appear ‘hairy’ beneath a microscope due to radial projections from their surface.

Question 18

Where do abnormal cells accumulate in hairy cell leukaemia?

Answer 18

Bone marrow–> anemia, thrombocytopenia, infections

Question 19

How does one diagnose hairy cell leukaemia?

Answer 19

Peripheral blood morphology.
Flow cytometry.
Bone marrow biopsy.

Question 20

Prognosis of hairy cell leukaemia?

Answer 20

May respond well to certain chemotherapies.

Question 21

Characteristics of B cell prolymphocytic leukaemia?

Answer 21

Very rare.
Aggressive.
Poor prognosis.

Question 22

Some characteristics of T prolymphocytic leukaemia?

Answer 22

Very high WCC.
Skin invlovement.
Serous effusions.

Question 23

Some characteristics of large granular lymphocyte leukaemia?

Answer 23

Cytopenias - anaemia, neutropenia

Associated with rheumatoid arthritis.

Question 24

Characteristics of adult T-cell leukaemia?

Answer 24

``` Commonly seen in Caribbean and Japan. Associated with HTLV1 virus associaton. Signs+symptoms: - skin lesions - hepatosplenomegaly - lymphadenopathy - hypercalcaemia ```

Question 25

What is multiple myeloma (plasma cell myeloma)?

Answer 25

A neoplasm of plasma cells that infiltrate the bone marrow and disrupt regular function of the bone marrow. Tissue damage may be a feature.

Question 26

Group of people in which MM is mostly seen?

Answer 26

Develop after 40y.o.a. | Peak in the 60's

Question 27

What is thought to be a key factor in the development of MM?

Answer 27

Overexpression of cyclin D.

Question 28

What may be a common complaint that is associated with MM?

Answer 28

An elderly patient who complains about persistent bone pain/back pain.

Question 29

What are the clinical features of MM?

Answer 29

Bone pain - RANKL activation--> stimulates osteoclast activity (bone lesions). Anaemia - lethargu, weakness, pallor, dyspnoea, tachycardia. Recurrent infections- neutropenia, lack of normal Ig. Renal- failure (calculi due to hypercalcaemia, Ig's), polyuria, polydipsia, anorexia. Bleeding- paraprotein interferes with platelets and coagulation factors. Amyloidosis. Hyperviscosity- haemorrhage, loss of vision, CNS sx, neuropathies, cardiac failure.

Question 30

Diagnosis of MM?

Answer 30

Serum and urine protein electrophoresis looking for monoclonal protein. Increased clonal plasma cells in bone marrow. Increased serum calcium. Cytogenetics and FISH

Question 31

Pneumonic for MM symptoms?

Answer 31

C - hypercalcaemia R - renal impairment A - anaemia B - bone involvement

Question 32

What is seen in a trephine biopsy in MM?

Answer 32

Diffuse infiltrate of plasma cells.

Question 33

Immunophenotyping of MM?

Answer 33

Monoclonal Ab staining. (Light chain)

Question 34

Other investigations to diagnose MM?

Answer 34

Presence of paraproteins (mostly IgG). Urine BJP - bence jones protein (monoclonal globulin protein) Anaemia (normochromic/normocytic) Neutropenia/thrombocytopenia High ESR and rouleaux formation Skeletal survey - osteolytic lesions or osteoporosis.

Question 35

Management (supportive) of MM?

Answer 35

Renal: rehydrate, management of hypercalcaemia and hyperuricaemia Bone disease: biphosphonates Anaemia and infections: transfusions, antibiotics, Ig, antifungals Bleeding: plasmapheresis

Question 36

Management(specific) of MM?

Answer 36

Intensive - younger patients- intensive chemo | Non-intensive: oral chemo, steroids, thalidomide

Question 37

Prognosis of MM?

Answer 37

Depends on genetics and disease burden. A few years with non-intense chemo. Variable.

Question 38

What is MGUS?

Answer 38

Monoclonal gammopathy of undetermined significance. Is a precursor of myeloma. No clinical complications at this stage.

Question 39

What is plasma cell leukaemia?

Answer 39

When large amounts of circulating plasma cells. | Rare + poor prognosis.

Question 40

What is amyloidosis?

Answer 40

A group of disorders --> deposition of protein in fibrillar form extracellularly. *disrupts organ/tissue function.

Question 41

Amyloidosis: inheritance? Pattern of spread?

Answer 41

Is congenital or acquired. | Focal or systemic.

Question 42

Systemic effects of amyloidosis?

Answer 42

Heart - failure Nerves - neuropathy, carpal tunnel Kidneys - failure Tongue - macroglossia