Lymphoma 2: Chronic Lymphocytic Leukaemia and Lymphoproliferative disorder quiz

Question 1

HL: Diagnosis and Staging, Tx and Prognosis

Answer 1

Question 2

Lymphoma morphology process

Answer 2

Question 3

HL: epidemiology

Answer 3

1% of all cancer
M>F (women sclerosis sub-type more often)
Bimodal age incidence: 20-29 (most common), >60 (smaller peak)

Question 4

HL: Signs and Sx

Answer 4

Painless enlargement of lymph nodes (-> may cause obstructive symptoms/signs)

• B symptoms: fever, night sweats, weight loss
• rarely: pruritus, alcohol-induced pain

Question 5

Nodular sclerosino HL sub-type

Answer 5

• F > M (20-29yo)
• Neck nodes and a mediastinal mass; may have B symptoms
• Spreads contiguously
• Needs tissue diagnosis

Question 6

HL classification

Answer 6

Classical HL:

• Nodular sclerosing 80% Good prognosis (causes the peak incidence in young women)
• Mixed cellularity 17% Good prognosis
• Lymphocyte rich (rare) Good prognosis
• Lymphocyte depleted (rare) Poor Prognosis

Nodular Lymphocyte predominant HL 5% (disorder of the elderly multiple recurrences)

Question 7

Staging of HL

Answer 7

• FDG-PET / CT scan
• Biopsy if other sites infilitrated

The diaphragm is key for staging  see diagram above…

Question 7

Staging of HL

Answer 7

• FDG-PET / CT scan
• Biopsy if other sites infilitrated

The diaphragm is key for staging  see diagram above…

Question 8

HL tx

• All patients with HL should receive chemotherapy however, radiotherapy is also often given after chemotherapy because HL is highly responsive to radiotherapy to clear up remaining cells
• Combined modality = radiotherapy and chemotherapy used
• Chemo and radiotherapy combined can lead to a HIGH risk of reoccurrence

Answer 8

Question 9

Outcome of HL therapy

Answer 9

Question 10

HL Tx dilemma

Answer 10

Treatment dilemma:

• HL is curable (~80%)
• Intensify therapy → more cures (>80%) but more secondary cancers (>10%)
• Reduce therapy → less secondary cancers (<10%) but less cures (<80%)

Non-Hodgkin’s Lymphoma

Question 11

NHL General

Answer 11

Question 12

Different types of NHL and their clinical behaviour

Answer 12

Question 13

Managing NHL

Answer 13

Question 14

Common and interesting lymphomas

Answer 14

• COMMON = DLBCL, FL
• INTERESTING = H. pylori MALToma, EATL, HIV-associated

Question 15

DLBC NHL (HIGH-GRADE, AGGRESSIVE)

Answer 15

• Common form of NHL (30-40% of all NHLs)
• Aggressive / high-grade
• Prognosis and treatment determined by:
  
  • Histological diagnosis
  • Anatomical stage
  • IPI (International Prognostic Index)

Question 16

DLBCL Tx

Answer 16

Question 17

Follicular NHL (LOW-GRADE/INDOLENT) features

Answer 17

• Indolent lymphoma
• 35% of NHL
• Associated with a t(14; 18) → over-expression of bcl-2 (an anti-apoptotic protein)
• Used a FLIPI score (a modified version of IPI)
• Incurable (median survival 12-15 years; requires 2-3 chemotherapy schedules over this period)

Question 18

Follicular NHL (LOW-GRADE/INDOLENT) initial tx options

Answer 18

Question 19

Extra-nodal Marginal Zone Lymphomas

Answer 19

Question 20

Enteropathy Associated T-cell Lymphoma (EATL)

Answer 20

Question 21

CLL definition and epidemiology

Answer 21

• Proliferation of mature B cells
• Epidemiology:
  
  • Most common (UK = 4.2/100,000/year) leukaemia in West
  • Tends to affect Caucasians
  • Median age at presentation: 72 years (10% aged <55yo)
  • Relatives have 7 x increased risk

Question 22

CLL Lab findings

Answer 22

• Lymphocytosis (5-300 x 10⁹/L)
• Smear cells (weak cells so break when put on a slide)
• Normocytic normochromic anaemia
• Thrombocytopaenia
• Bone marrow lymphocytic replacement of normal marrow elements

NOTE: as this is an indolent leukaemia, it is often only picked up during routine blood tests for other reasons

Question 23

How do we check maturity of B cells (what about T cells?)

Answer 23

• Maturity of B cells can be determined from its antigen expression, identified through immunophenotyping– B-cells express different antigens as they progress through development – mature B-cells specifically express:
  
  • sIg
  • CD-19

Question 24

CLL Prognosis: VH mutations

Answer 24

* VH = variable heavy chain (the part that undergoes somatic hypermutation by VDJ recombination) * Pre-germinal centre B cells will have Ig-genes (VH genes) that have **_NOT_** undergone somatic hypermutation. In other words, they are UNMUTATED and conform precisely to the germline sequence * Once antigen selection is complete, the **_B cell has undergone somatic mutations in the VDJ region_** and so it can be said that the B cell has had it’s VH region mutated (physiologically), post-germinal centre * Half of CLL patients have MUTATED VH (i.e. arising from post-germinal centre cells) and half have UNMUTATED VH (i.e. arising from pre-germinal centre cells)  **_prognosis much worse in patients with an UNMUTATED VH_** * **_Mutated = 25 years survival_** * **_Unmutated = 8 years survival_**

Question 25

CLL Prognosis: biological prognostic factors which common genetic abnormality is important

Answer 25

* There is a collection of common genetic abnormalities that are screened using FISH: * Deletion of 13q ~133 months survival * Trisomy 12 ~114 * Deletion of 11q (ATM) ~79 * Deletion of 17p (TP53)  loss of p53 tumour suppressor gene * The most important is **DELETION of 17p (TP53)** * These don’t tend to respond to chemotherapy

Question 26

CLL clinical issues

Answer 26

* Although high lymphocytes, the cells are mono-clonal and so NOT useful for antibody production and an abundance of non-functioning B cells  hypogammaglobulinemia as normal B cells are being suppressed * This leads to increased risk of infection (e.g. pneumonia, sinusitis) * Healthy bone marrow will become suppressed leading to bone marrow failure (anaemia, infection, bleeding) * Malignant lymphocytes can spread to lymphoid organs (e.g. lymph nodes, spleen) * Although this is an indolent disease, there is a 1% chance every year that CLL can acquire more mutations and undergo a **RICHTER TRANSFORMATION** (become a high grade lymphoma) * Presence of a population of malignant B cells  deregulation of the surviving normal B cell population * This can result in autoimmune disease (e.g. autoimmune haemolytic anaemia)

Question 27

CLL treatment (3)

Answer 27

(1) **Supportive** (as 50% of CLL-related deaths due to infections) * Vaccination (_flu_, _pneumococcus_) – *no live vaccines* *(i.e. VZV)* * Anti-infective prophylaxis and treatment * Acyclovir for viral infections * PCP prophylaxis for those that are immunosuppressed * IVIG for those with hypogammaglobulinaemia and recurrent bacterial infections (2) **Specific Scenarios**: * High-Grade (Richter) Transformation  treat as high grade lymphoma (R-CHOP) (3) **Leukaemia-directed Treatment**: * Tailored to the patient * Elderly * Young * Need irradiated blood products if they are at risk of transfusion-associated graft-versus-host disease * Incurable by chemo → watch and wait preferred over any active treatment, esp. in elderly patients * The decision to treat is often dependent on the age and comorbidities of the patient * The aim of therapy is to establish remission

Question 28

CLL indications for tx (i.e. when to stop watching and waiting)

Answer 28

* Progressive lymphocytosis (count doubling \< 6 months) * Progressive bone marrow failure (Hb \< 100; Platelets \< 100; Neutrophils \< 1) * Massive or progressive lymphadenopathy/splenomegaly * Systemic symptoms (B symptoms)

Question 29

CLL 1st line chemo-immunotherapy (TP53 intact)

Answer 29

(1) **FCR** or **R-Bendamustine** (combination chemotherapy) * Fludarabine * Cyclophosphamide * Rituximab (anti CD20 moab) (2) **Obinutuzumab** (anti CD20) + **Chlorambucil** (single agent chemo) (3) Supportive care only

Question 30

High-risk CLL cases

Answer 30

Patients with TP53/17p deleted CLL 1^st Line Refractory disease or early relapse (\<24 months)

Question 31

CLL new agent tx (VERY EXPENSIVE)

Answer 31