Lymphoid Malignancies

Question 1

What does leukaemia actually mean?

Answer 1

White blood

Question 2

What is lymphoma?

Answer 2

Cancer of lymphoid origin which can present with

• Lympadeonpathy OR
• Extranodal involvement OR
• Bone marrow involvement

-Systemic B symptoms including weight loss (>10 % in 6 months), fever, night sweats, pruritus, fatigue

Question 3

How is lymphoma defined?

Answer 3

By the malignant cell characteristics

Question 4

What investigation tells us what type of lymphoma it is?

Answer 4

Biopsy

Question 5

What investigations tells us where the lymphoma is?

Answer 5

Clinical examination and imaging

Question 6

What is non-Hodgkin lymphoma?

Answer 6

A group of ~50 subtypes of lymphoma

Question 7

What can non-Hodgekin lymphoma be divided into?

Answer 7

• High grade

- Low grade

Question 8

Give examples of lymphoproliferative disorders.

Answer 8

• Acute lymphoblastic leukaemia (ALL)
• Chronic lymphocytic leukaemia (CLL)
• Hodgkin lymphoma
• Non-Hodgkin lymphoma (NHL)

Question 9

What is a high grade non-Hodgkin lymphoma?

Answer 9

A diffuse large B cell lymphoma

Question 10

How common is each type of lymphoma?

Answer 10

Most common

• High grade NHL
• Low grade NHL
• Hodgkin lymphoma
• CLL
• ALL

Question 11

What is acute lymphoblastic leukaemia?

Answer 11

Neoplastic disorder of lymphocytes

Question 12

How is acute lymphoblastic leukaemia diagnosed?

Answer 12

By >20% lymphoblasts present in bone marrow

Question 13

What is the epidemiology of acute lymphoblastic leukaemia?

Answer 13

• Incidence 1-2/100,000 population/year
• 75% cases occur in children < 6 years
• 75-90% cases are of B-cell lineage

Question 14

How does acute lymphoblastic leukaemia usually present?

Answer 14

Present with 2-3 week history of bone marrow failure or bon/joint pain

Question 15

What is the standard treatment for acute lymphoblastic leukaemia?

Answer 15

• Induction chemotherapy to obtain remission
• Consolidation therapy
• CNS directed treatment
• Maintenance treatment for 18 months

Question 16

What other treatment is there for acute lymphoblastic leukaemia?

Answer 16

• Stem cell transplantation (if high risk)
• Bispecifc T-cell engagers (BiTe molecules): e.g. Blinatumumab
• CAR (chimeric antigen receptor T-cells)

Question 17

How is CAR treatment carried out?

Answer 17

• Patient/ healthy 3rd party T-cells harvested
• Transfected to express a specific T-cell receptor expressed on leukaemia cells (CD19)
• Expanded in vitro
• Re-infused into patient

Question 18

How does T-cell immunotherapy associated neurotoxicity present?

Answer 18

• Confusion with normal conscious level

- Seizure, headache, focal neurology, coma

Question 19

How does T-cell immunotherapy associated cytokine release syndrome present?

Answer 19

• Fever, hypotension, dyspnoea

- CAR T-cell effect correlated to presence of CRS (significant number require ITU support)

Question 20

What are poor risk factors associated with acute lymphoblastic leukaemia?

Answer 20

• Increasing age
• Increased white cell count
• Immunophenotype (more primitive forms)
• Cytogenetics/molecular genetics: t(9;22); t(4;11)
• Slow/poor response to treatment

Question 21

What are the outcomes of acute lymphoblastic leukaemia?

Answer 21

Adults with ALL

• Complete remission rate 78–91%
• Leukaemia-free survival at 5y 30–35%

Children with ALL

• 5y overall survival ~90%
• Poor risk patients (slow response to induction or Philadelphia positive) 5y OS 45%

Question 22

What is the typical presentation of acute lymphoblastic leukaemia?

Answer 22

• Bone marrow failure +/- raised white cell count

- Bone pain, infection, sweats

Question 23

How is chronic lymphoblastic leukaemia diagnosed?

Answer 23

-Blood > 5 x 109/L lymphocytes
-Bone marrow > 30% lymphocytes
-Characteristic immunophenotyping
(B-cell markers (CD 19, 20, 23) & CD5 positive)

Question 24

What is the incidence of CLL?

Answer 24

• > 1700 new cases CLL per year in the UK
• Commonest leukaemia worldwide
• M:F 2:1
• Occasionally familial
• Rare in far East

Question 25

How does CLL present?

Answer 25

Often asymptomatic Frequent findings - Bone marrow failure (anaemia, thrombocytopenia) - Lymphadenopathy - Splenomegaly (30%) - Fever and sweats (< 25%) Less common findings: - Hepatomegaly - Infections - Weight loss

Question 26

What conditions/states are associated with CLL?

Answer 26

- Immune paresis (loss of normal immunoglobulin production) | - Haemolytic anaemia (20% have positive direct antiglobulin test, 8% clinical evidence of haemolytic anaemia)

Question 27

What system is used to stage CLL?

Answer 27

Binet

Question 28

What are the stages of CLL according to the Binet system?

Answer 28

Stage A - <3 lymph nodes - Same survival as age matched controls Stage B - 3 or more lymph node areas - ~8 year survival Stage C - Stage B + anaemia ro thrombocytopenia - ~6 years survival

Question 29

What are the indications for treatment in CLL?

Answer 29

- Progressive bone marrow failure - Massive lymphadenopathy - Progressive splenomegaly - Lymphocyte doubling time <6 months or >50% increase over 2 months - Systemic symptoms - Autoimmune cytopenias

Question 30

What is the treatment for CLL?

Answer 30

- Often nothing: “watch and wait” - Cytotoxic chemotherapy e.g. fludarabine, bendamustine - Monoclonal antibodies e.g. Rituximab, obinutuzamab - Novel agents: (Bruton tyrosine kinase inhibitor eg ibrutinib) (PI3K inhibitor eg idelalisib) (BCL-2 inhibitor eg venetoclax)

Question 31

What are poor prognostic factors in CLL?

Answer 31

- Advanced disease (Binet stage B or C) - Atypical lymphocyte morphology - Rapid lymphocyte doubling time (<12 mth) - CD 38+ expression - Loss/mutation p53; del 11q23 (ATM gene) - Unmutated IgVH gene status

Question 32

How does lymphoma present?

Answer 32

- Lymphadenopathy/ hepatosplenomegaly - Extranodal disease - “B symptoms” - Bone marrow involvement

Question 33

How is lymphoma assessed and staged?

Answer 33

- Lymph node biopsy - CT scan - Bone marrow aspirate and trephine

Question 34

What are the stages of lymphoma?

Answer 34

-Can be classified by presence of B symptoms - Stage 1= 1 node involved - Stage 2= 2 nodes - Stage 3= multiple nodes - Stage4= node and hepatosplenomegaly

Question 35

How is non-Hodgkin lymphoma classified?

Answer 35

- Lineage (B-cell or T-cell) (Majority are B-cell in origin) - grade of disease (high grade or low grade) - Histological features of disease

Question 36

What are the features of low grade NH lymphoma?

Answer 36

- Indolent, often asymptomatic - Responds to chemotherapy but incurable - Median survival varies by subtype

Question 37

What are the features of high grade NH lymphoma?

Answer 37

- Aggressive, fast-growing - Require combination chemotherapy - Can be cured, but again varies widely

Question 38

Give examples of specific NH lymphoma disease entities.

Answer 38

Diffuse large B-cell lymphoma - Commonest subtype of lymphoma (of any kind) - High-grade lymphoma Follicular lymphoma - 2nd commonest subtype of lymphoma - Low-grade lymphoma

Question 39

How is NH lymphoma treated?

Answer 39

Combination chemotherapy, typically anti-CD20 monoclonal antibody and chemo

Question 40

What is the epidemiology of Hodgkin lymphoma?

Answer 40

- 30% of all lymphomas - Bimodal age curve with 1st peak at 15-35y and 2nd peak later in life - M:F 1.9:1 - association with Epstein Barr virus; familial and geographical clustering

Question 41

What is the treatment for Hodgkin lymphoma?

Answer 41

- Combination chemotherapy (ABVD) - +/- radiotherapy - Monoclonal antibodies (anti-CD30) - Immunotherapy (checkpoint inhibitors) - Use of PET scan to assess response to treatment and to limit use of radiotherapy