Lymphoid malignancy

Question 1

Features of lymphoma?

Answer 1

• Can present with enlarged lymph nodes (lymphadenopathy)
• with extranodal involvement
• with bone marrow involvement
• Weight loss (> 10% in 6 months), fever, night sweats, pruritis, fatigue

Question 2

How many types of lymphoma are there?

How can we tell what type?

Answer 2

• > 50 different disease entities, defined by the malignant cell characteristics
• Biopsy (e.g. lymph node, bone marrow) tells us what type it is
• Clinical examination and imaging (e.g. CT) tell us where it is, not what it is
• Lymphoma vs leukaemia – bone marrow involvement

Question 3

What are the main lymphoproliferative disorders?

Answer 3

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

Question 4

What is Acute lymphoblastic leukaemia (ALL)?

Answer 4

• Neoplastic disorder of lymphoblasts
• Diagnosed by > 20% lymphoblasts present in bone marrow

Question 5

Epidemiology of ALL?

Answer 5

• Incidence 1-2/100,000 population/year
• 75% cases occur in children < 6 years
• 75-90% cases are of B-cell lineage
• Present with 2-3 week history of bone marrow failure or bone/joint pain

Question 6

What would common findings on bloods be for ALL?

Answer 6

• Haemoglobin 38 g/L (120-140)
• White cell count 370 x 109/L (4-11)
• Platelets 68 x 109/L (150-400)
• Bone marrow 90% B-lymphoblasts

Question 7

What is the treatment of ALL?

Answer 7

• Standard treatment
  
  • Induction chemotherapy to obtain remission
  • Consolidation therapy
  • CNS directed treatment
  • Maintenance treatment for 18 months
• Stem cell transplantation (if high risk)

Question 8

What are poor RF for ALL?

Answer 8

• 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 9

What are the likely outcomes for ALL?

Answer 9

• 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 10

ALL useful info:

Answer 10

• Typical presentation:
  
  • Bone marrow failure +/- raised white cell count
  • Bone pain, infection, sweats
• Treated with multi-agent intensive chemotherapy +/- allogeneic stem cell transplant

Question 11

How do we make a diagnosis of CLL?

Answer 11

Chronic lymphocytic leukaemia

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

Question 12

CLL incidence?

Answer 12

• Commonest leukaemia worldwide
• 2 males: 1 female

Question 13

How does CLL present?

Answer 13

• Often assymptomatic at presentation
• Frequent findings:
  
  • Bone marrow failure (anaemia, thrombocytopenia)
  • Lymphadenopathy
  • Splenomegaly (30%)
  • Fever and sweats (< 25%)

Question 14

What is the staging system for CLL?

Answer 14

Binet

A. <3 lymph node areas, survival same as matched controls

B. 3 or more lymph node areas, survival 8 yrs

C. Stage B + anaemia or thrombocytopenia, survival 6 yrs

Question 15

What are indications for treatment in CLL?

Answer 15

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

Question 16

How can we treat CLL?

Answer 16

• Often nothing – “watch and wait” - 50% patients receive chemo, 50% receive no treatment
• Cytotoxic chemotherapy e.g. fludarabine, bendamustine
• Monoclonal antibodies e.g. Rituximab, obinutuzamab

Question 17

What are poor prognostic factors for CLL?

Answer 17

• Advanced disease (Binet stage B or C)
• Atypical lymphocyte morphology
• Rapid lymphocyte doubling time (<12 mth)
• CD38+ expression

Question 18

How does lymphoma present?

Answer 18

• lymphadenopathy/hepatosplenomegaly
• Extranodal disease
• “B symptoms”
• bone marrow involvement

Question 19

How do we stage lymphoma?

Answer 19

• lymph node biopsy/ CT scan/ bone marrow aspirate and trephine

Question 20

How do we stage lymphoma?

Answer 20

Question 21

Non-Hodgkin lymphoma

How are they classified?

Answer 21

• 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 22

How are Non-Hodgkin lymphoma graded?

Answer 22

• Low grade lymphoma
  
  • Indolent, often asymptomatic
  • responds to chemotherapy but incurable
  • median survival varies by subtype
• High grade lymphoma
  
  • Aggressive, fast-growing
  • Require combination chemotherapy
  • Can be cured, but again varies widely

Question 23

What are a couple of specific disease entities of NHL?

Answer 23

• Diffuse Large B cell lymphoma
• Follicular lymphoma

Question 24

Features of diffuse large B cell lymphoma?

Answer 24

• Commonest subtype of lymphoma (of any kind)
• High-grade lymphomaa

Question 25

Features of follicular lymphoma?

Answer 25

• 2nd commonest subtype of lymphoma
• Low-grade lymphoma

Question 26

How are diffuse large b cell and follicular lymphoma treated?

Answer 26

• Both are treated with combination chemotherapy – typically anti-CD20 monoclonal antibody + chemo

Question 27

Brief epidemiology of Hodgkin Lymphoma?

Answer 27

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

Question 28

What is the treatment of Hodgkin lymphoma?

Answer 28

• 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