11.4 Introduction to Haematologic Malignancies Flashcards
What is leukaemia?
Malignant process involving excess of clonal white blood cells
Acute vs chronic leukaemia
Excess:
Acute: immature cells; “blasts”
Chronic: end-stage cells
Leukaemia vs lymphoma
Leukemia: affects circulating WBCs
Lymphoma: localised to lymph nodes
What is the incidence of haematological malignancies in adults?
20%
List some risk factors for haematological malignancies
- Smoking
- Genetic abnormalities
- Family history
- Exposure to carcinogens/radiation
- Viral infections (e.g. Epstein Barr Virus)
Indolent vs aggressive lymphoma; which is curable, and which is incurable?
Indolent: slow cellular accumulation (incurable)
Aggressive: rapid cellular division (curable)
Why is the term “metastasis” not commonly used in the context of lyphoma or leukaemia?
- Lymphocytes usually migrate around the body
- Therefore, the movement of these cells is not metastasis, but regular movement
“Infiltrate” vs “involved with” in terms of haematological malignancies
Infiltrate: a cancerous lymphocyte has moved to an area where it does not belong (e.g. lymph node cell in skin)
Involved with: cancerous lymphocyte in an area that it is local to
What percentage of cells in the peripheral blood/bone marrow must be blast cells for a diagnosis of acute lymphoblastic leukaemia?
> =20%
What structure(s) differentiate between hodgkins and non-hodgkins lymphoma?
Reed-Sternberg cell (multinucleated giant cell made of lymphocytes)
Hodgkins has one, non-hodgkins doesn’t.
Which type of lymphocytes does hodgkin’s lymphoma affect? Therefore, is it acute or chronic?
- Affects B lymphocytes (mature)
- Therefore, it is chronic
List cancers in B cells, T cells, and NK cells in order from most to least common
- B Cells (85%)
- T Cells (15%)
- NK Cells (<1%)
How are indolent haematological malignancies most commonly found?
- Incidentally
- They are found on routine blood tests, or when imaging
- After all, if they are not causing the patients any symptoms (since the cells are slow replicating), how would we notice them?
How can lymphoma cause splenomegaly?
- Lymphocytes are homed to the spleen
- As they rapidly proliferate, the spleen is enlarged
What are some signs of aggressive lymphoma?
- Rapidly enlarging lymphadenopathy
- High cell turnover = high LDH
- Bone marrow infiltration would cause anaemia, thrombocytopaenia, neutropaenia
- Constituional symptoms (explained on another card)
Is bone pain more common in lymphoma or multiple myeloma?
Myeloma
What are constitutional B symptoms?
- Fever (>38.3°C)
- Drenching night sweats
- Weight loss (>10% body weight over few months) -> intentional or unintentional
What is the most common form of lymphoma?
Diffuse large B cell lymphoma (DLBCL)
Is DLBCL aggressive or indolent?
Aggressive
Typical blood work results for DLBCL
- Mild anaemia
- LDH 450
What scans are performed in patients with suspected lymphoma? Why?
- PET scan: activity in tissues
- CT scan: anatomy
Nodal vs extranodal blood/lymph cancers
Nodal: Isolated within lymph nodes and spleen
Extranodal: Anything outside of this
Ann arbor staging classifies the spread of lyphoma. What are stage 1, 2, 3, and 4?
Stage 1: 1 site of disease
Stage 2: 2+ site on same side of diaphragm
Stage 3: Disease on both sides of diaphragm
Stage 4: Widespread involvement of extralymphoid sites
Explain the concept of sanctuary sites. Where are these sites located?
Sanctuary sites are areas where it is difficult for anti-cancer drugs to penetrate due to barriers. These include the brain, the eyes, and the testes
What factors influence the prognosis in cancer (particularly lymphoma?)
What kind of damage has it done?:
- LDH (how aggressive?)
- Cytopenia?
- What stage?
- Extranodal sites?
Patient related factors:
- Age?
- Comorbidities?
- Organ function?
- Frailty/disability?
Response to treatment:
- Depth of response
- Minimal residual disease
- Relapse time?
Why do we systemic therapy (like chemotherapy) for lymphoma?
- It is considered systemic
- We can’t cut it out, because these cells can exist all throughout the body
Rituximab cancer therapy mechanism. What other mechanisms can monoclonal antibodies use to kill haematologic malignancies?
- Monoclonal antibody for CD20; which is a B cell surface marker
- Causes immune destruction/removal of cancerous cells, or you can attach radioactive particles/chemotherapy that kill the cell once engulfed
There are other monoclonal antibodies. Not just this one.
Describe CAR-T cancer therapy
- Take out patient’s T cells
- Engineer them to kill cancer
- Put them back in
- KABOOM
Describe the genetics behind Follicular Lymphoma
- Translocation of antiapoptotic gene from chromosome 14-18
- Moved next to highly-expressed immunoglobulin gene
- Enhanced activity, leads to overproliferation
Describe the role of Reed-Sternberg cells in Hodgkin’s Lymphoma
- They command the rest of the immune system in such a way that drives the disease
- The actual amount of cancer burden is very low
What are the two most common age groups for Hodgkin’s
- Young adults (20-24)
- Older adults (80+)
What is the most common cause of death in patients with hodgkin’s lymphoma?
Second malignancy
What are some common comorbidities that arise alongside T cell lymphoma?
- Shingles
- Cold sores
- Urticaria
Chornic Lymphocytic Leukaemia can be reclassified as a lymphoma. What is it called then?
Small lymphocytic lymphoma (SLL)
Mutated vs unmutated Chronic Lymphocytic Leukaemia. Which generally requires therapy, and which doesn’t
Mutated: Memory B Cells
Unmutated: Naive B Cells
Most common way of finding Chronic Lymphocytic Leukaemia (CLL)?
Incidental findings on CBC
Presenting symptoms of chronic lymphocytic leukaemia
- Recurrent infections
- Constitutional symptoms
- Splenomegaly, adenopathy
- Rashes
Describe the three stages of Binet CLL staging
Stage A: No anaemia, no thrombocytopenia, <3 lymph node areas
Stage B: No anaemia/thrombocytopenia, >3 lymph node areas
Stage C: Anaemia, thrombocytopenia, any number of lymph sites
What is hypogammaglobulinaemia?
Reduced serum antibody levels
Describe multiple myeloma, including cell of origin
- Cancer of plasma cells in bone marrow
- Decreases production of other cells, and causes bone pain
Describe the 2 mechanisms by which plasma cells can decrease haematopoiesis in multiple myeloma
- Crowding out
- Communicating with microenvironment to reduce haematopoiesis
Do the hyperproduced antibodies in multiple myeloma even work?
Nope. Not good.
Which two antibody isotypes are most commonly mutated in multiple myeloma?
- IgG (2/3)
- IgA (1/3)
Peripheral blood findings in myliple myeloma
Presence of circulating plasma cells
Bone marrow aspirate findings of multiple myeloma
Large presence of plasma cells
Explain the CRAB pnemonic for multiple myeloma features
- Calcium high
- Renal insufficiency
- Anemia
- Bone lytic lesions, bone pain
How does multiple myeloma cause renal failure?
- Abnormal antibodies have toxic effect on distal tubule
- Can block nephrons entirely
What is MGUS? Does it always lead to myeloma?
- Monocllonal gammopathy of undetermined significance
- Will not always leads to cancer
