Haematological Malignancies

Question 1

What is Hodgkins Lymphoma?

Answer 1

Abnormal growth and spread of cells of the lymphatic system. Commonly find abnormal numbers of Reed-Sternberg cells.

Question 2

Hodgkins Lymphoma RF:

Answer 2

Age- 20-40yrs old. >50yrs old.
FHx
Male
EBV

Question 3

Types of Hodgkins Lymphoma:

Answer 3

Nodular sclerosis Hodgkins Lymphoma
Mixed cellularity Hodgkins Lymphoma
Lymphocyte depleted Hodgkins Lymphoma
Lymphocyte rich Hodgkins Lymphoma

Question 4

Staging of Hodgkins Lymphoma:

Answer 4

I- Limited to one LN/organ.
II- Limited to LN/organs either all above or all below the diaphragm.
III- Spreading onto both sides of the diaphragm.
IV- More serious, affecting any part of the body including lungs.

Type A- Non serious/few symptoms
Type B- Constitutional symptoms (inc weight loss, night sweats, fever, spleno/hepaomegaly)
X- Site of tumour bulk
S- In the spleen.

Question 5

Investigating Hodgkins Lymphoma:

Answer 5

Physical examination- swollen axilla/cervical/groin LN, areas of rashes, splenomegaly.
Blood test (FBC, U+Es, LFTs, LDH, Ca2+) and blood film
LN biopsy- look for Reed-Sternberg cells.
Imaging (PET scan with CT for staging)
Bone marrow aspiration.

Question 6

Treating Hodgkins Lymphoma:

Answer 6

Chemo and radiotherapy
Chemotherapy alone
If returns after treatment then consider bone marrow transplant. Take SC from BM and freeze. Then use chemo/radiotherapy to kill cancerous cells. Transplant the SC after they have thawed.

Question 7

What is Non-Hodgkins lymphoma?

Answer 7

Tumour of the lymphatic system, get abnormal growth of lymphocytes. Can spread to lymphatic organs i.e. tonsils, spleen, thymus, BM etc Or can even spread outside of the lymphatic system.

Question 8

Non-Hodgkins lymphoma RF:

Answer 8

Not many obvious RF. But include:
>60yrs (although can happen any age)
Chemical exposure i.e. weed/insect killer.
HIV, EBV, H.pylori infection.
Immunosuppressive drugs.

Question 9

Types of Non-Hodgkins lymphoma:

Answer 9

> 80 types.
Separate into low grade and high grade, then into B cell and T cell, where B is more common than T.
High grade are more aggressive but can be cured i.e Diffuse large B cell lymphoma or Burkitt’s lymphoma. Low grade are more slow progressing but cant be cured i.e. follicular lymphoma, marginal zone lymphoma.

Question 10

Staging Non-Hodgkins lymphoma:

Answer 10

Ann-Arbor staging.

Question 11

Investigating Non-Hodgkins lymphoma:

Answer 11

Physical examination- swollen axilla/cervical/groin LN, areas of rashes, splenomegaly.
Blood test (FBC, U+Es, LFTs, LDH, Ca2+) and blood film
LN excision biopsy (preferable), otherwise core biopsy.
Imaging (CT, MRI more likely used than PET)
Bone marrow aspiration.

Question 12

Treating Non-Hodgkins lymphoma:

Answer 12

Low grade- Watch and wait.
High grade- Chemotherapy.
Can be followed by radiotherapy.
Targeted drug therapies either alone, or as a second treatment if the tumour returns.
Bone marrow transplant if others not effective.

Question 13

Use of BM aspiration:

Answer 13

1) Make slides from the aspirate
2) Flow cytometry to look for markers on the cells.
3) Cytogenetics- including karyotyping- taking upto weeks but use when we dont know what mutation we are looking for. FISH- takes upto 24hrs but use when we know the mutation we are looking for- using a probe.

Question 14

Signs/Symptoms of Hodgkins Lymphoma:

Answer 14

Painless swelling of lymph nodes in your neck, armpits or groin
Persistent fatigue
Fever
Night sweats
Unexplained weight loss
Severe itching
Increased sensitivity to the effects of alcohol or pain in your lymph nodes after drinking alcohol

Question 15

Signs/Symptoms of Non-Hodgkins Lymphoma:

Answer 15

Swollen lymph nodes in your neck, armpits or groin
Abdominal pain or swelling
Chest pain, coughing or trouble breathing
Persistent fatigue
Fever
Night sweats
Unexplained weight loss

Question 16

Leukaemia vs Lymphoma:

Answer 16

Leukaemia is restricted to the BM +/- blood.

Question 17

What is AML?

Answer 17

Cancer of the myeloid progenitor cells. It s rapidly progressing.

Question 18

Signs/Symptoms of AML:

Answer 18

Fever
Bone pain
Lethargy and fatigue
Shortness of breath
Pale skin
Frequent infections
Easy bruising
Unusual bleeding, such as frequent nosebleeds and bleeding from the gums

Question 19

RF for AML:

Answer 19

Increasing age- common in >65yrs
Male
Exposure to harmful radiation/chemicals
Previous chemotherapy
Smoking
Blood disorders
Genetic disorders i.e. Downs syndrome

Question 20

Diagnosis of AML:

Answer 20

Patients usually have high WBC count with anaemia and thrombocytopenia. Can also present as a pancytopenia.
Confirm with BM biopsy- see immature blast cells.
Subtype AML using slides, flow cytometry and cytogenetics.

Question 21

Prognosis of AML:

Answer 21

Dependent on patient health, subtype of AML and age.

Question 22

Treatment of AML:

Answer 22

Two phases- Remission induction therapy and consolidation therapy.
Phase one includes chemo +/- targeted therapy.
Phase two includes targeted therapy.

Question 23

What is CML?

Answer 23

Cancer of the myeloid lineage; increasing WBC (except lymphocytes), but normal/below normal RBC/platelets.

Question 24

Signs/Symptoms of CML:

Answer 24

Bone pain
Easy bleeding
Feeling full after eating a small amount of food
Feeling run-down or tired
Fever
Weight loss without trying
Loss of appetite
Pain or fullness below the ribs on the left side
Night sweats

Question 25

RF for CML:

Answer 25

``` Old age Male Radiation exposure. In CML get translocation t(9:22) of the Philadelphia chromosome this creates the BCR-ABL gene which increases the number of tyrosine kinase in the body. Tyrosine kinase promotes tumour growth. FHx is not a RF!!! ```

Question 26

Diagnosis of CML:

Answer 26

Physical exam looking at LN and enlarged spleen. Blood looking at number of cells. Confirm with BM sample. Testing for the philadelphia chromosome using FISH or for the BCR-ABL gene using PCR.

Question 27

Prognosis of CML:

Answer 27

Depends on the type. Chronic- early stage with the best prognosis. Accelerated- transitional stage, disease becomes more aggressive. Blast- Most aggressive and life threatening stage.

Question 28

Treatment of CML:

Answer 28

Treat with targeted therapy (tyrosine kinase inhibitor) including Imantinib. The effectiveness is measured through measuring the level of BCR-ABL present. IF not working then use alternative targeted therapy. Can use chemo alongside the targeted drug therapy.

Question 29

What is ALL?

Answer 29

Cancer affecting the lymphoid blast cells within the bone marrow/blood. Most common cancer in children but very curable, in adults it is less common and less curable. Over 65 have a worse prognosis and poorer response to treatment.

Question 30

Signs and symptoms of ALL:

Answer 30

``` Bleeding from the gums Bone pain Fever Frequent infections Frequent or severe nosebleeds Lumps caused by swollen lymph nodes in and around the neck, armpits, abdomen or groin Pale skin Shortness of breath Weakness, fatigue or a general decrease in energy ```

Question 31

RF for ALL:

Answer 31

Previous cancer treatment. Exposure to radiation. Genetic disorders; Downs syndrome.

Question 32

Diagnosis of ALL:

Answer 32

Blood tests BM XR, CT scan, USS.

Question 33

Prognosis of ALL:

Answer 33

The type of lymphocytes involved. The specific genetic changes present in your leukaemia cells Age Results from lab tests, such as the number of white blood cells detected in a blood sample

Question 34

Treatment of ALL:

Answer 34

Many phases of treatment: 1) Induction therapy- to kills most of the cancer cells. 2) Consolidation therapy- to ensure all the cells are killed. 3) Maintenance therapy- prevent regrowth of cancer cells, at this phase pts take a lower dose of treatment over years. During all stages, if the leukaemia is in the CNS then pts can have treatment injected into the fluid surrounding the spinal cord to protect it. Each phase can last a couple of years where treatments include radiotherapy, chemotherapy, targeted therapy or BM transplant.

Question 35

What is CLL?

Answer 35

Cancer of the mature lymphoid cells, chronic therefore slowly forming.

Question 36

Signs/Symptoms of CLL:

Answer 36

``` Enlarged, but painless, lymph nodes Fatigue Fever Pain in the upper left portion of the abdomen, which may be caused by an enlarged spleen Night sweats Weight loss Frequent infections ```

Question 37

RF for CLL:

Answer 37

Increasing Age White Exposure to harmful chemicals i.e. herbicides/insecticides FHx of cancer of the BM/blood Disorders causing XS lymphocytes i.e. monoclonal B lymphocytosis (MBL).

Question 38

Diagnosis of CLL:

Answer 38

Blood count- look for increase in number of lymphocytes. Flow cytometry/immunophenotyping to work out the lymphocytes involved. Analyse genetics using FISH.

Question 39

Prognosis of CLL:

Answer 39

Stage with CT/PET to then determine the prognosis. | Can go on to cause autoimmune haemolytic anaemia.

Question 40

Treatment of CLL:

Answer 40

Usually pt are treated through watch and wait, early treatment is not shown to give significant improvement. Begin treating when intermediate/advanced stage i.e. shows B symptoms, anaemia/thrombocytopenia suggestive of B, suppression, AIHA, massive lymphadenopathy/splenomegaly etc. Chemotherapy Targeted drug therapy Immunotherapy BM transplant

Question 41

What is Myeloma?

Answer 41

Abnormal replication of one plasma cell- the monoclonal protein produced is referred to as the paraprotein/M-protein. Almost always develops from benign MGUS where paraprotein are present at more lower and harmless levels.

Question 42

Signs/symptoms of Myeloma:

Answer 42

``` Bone pain, especially in your spine or chest Nausea Constipation Loss of appetite Mental fogginess or confusion Fatigue Frequent infections Weight loss Weakness or numbness in your legs Excessive thirst ```

Question 43

RF for Myeloma:

Answer 43

``` Increasing age Black Male FHx of multiple myeloma Personal Hx of MGUS. ```

Question 44

Complications of Myeloma:

Answer 44

Frequent infections Kidney failure Anaemia Bone problems

Question 45

Diagnosis of Myeloma:

Answer 45

Blood and urine tests looking for paraprotein. Bone marrow examination including FISH XR, CT, MRI, PET

Question 46

Prognosis of Myeloma:

Answer 46

If asymptomatic then watch and wait.

Question 47

Treatment of Myeloma:

Answer 47

``` Targeted therapy Chemotherapy Immunotherapy Corticosteroids Radiation therapy BM transplant ```

Question 48

SLiM CRAB:

Answer 48

Myeloma defining events: Sixty % BM plasmacytosis Light chain ratio >100 MRI lesion>5mm ``` Evidence of end organ damage: Ca2+- >2.75 Renal failure (CR>177) Anaemia (Hb<100) Bone lesion (1+ on XR/CT/PET) ``` Need >10% clonal population of BM plasma cells + paraprotein to diagnose a myeloma. Or 60% BM plasmacytosis needs treating.

Question 50

Myeloproliferative disorders:

Answer 50

Polycythaemia vera can develop into MF or AML Essential thrombocythamaemia can develop into MF or AML Myelofibrosis CML

Question 51

Essential thrombocythaemia

Answer 51

Picked up incidentally Risk of stroke/MI Fatigue

Question 52

ET mutation:

Answer 52

JAK2 CALA MPL Need any one of these for a diagnosis with the abnormal blood count.

Question 53

Thrombocytosis causes: | If not present then think ET.

Answer 53

``` Bleeding Infection/inflammation Trauma I.e.post surgery Autoimmune Iron deficiency anaemia paradox ```

Question 54

Polycythaemia Vera:

Answer 54

High Hb and haematocrit No other cause of increased Hb. Have JAK2, Ferratin (low), Exon 12, EPO (low). If still unclear then bone marrow biopsy.

Question 55

ET treatment:

Answer 55

Anti-platelet- used as prophylaxis. Pay attention to CVS risks. Hydroxycarbamide- suppresses BM production of normal cell.

Question 56

Increase Hb

Answer 56

``` Smoking Hypoxia Congenital heart defect- chronic hypoxia OSA (obstructive sleep apnoea) COPD Lung diseases Kidney defect EPO secreting tumour Liver disease Exogenous EPO Exogenous testosterone Testosterone secreting tumours High altitudes ```

Question 57

Polycythaemia Vera management:

Answer 57

``` Normal range is 40-50%, aim for 45%. Look at haematocrit to guide treatment. Hydroxycarbamide Anti platelet Venesection ```

Question 58

Myelofibrosis:

Answer 58

Fibrosis and scars of the BM, where cells are usually being made. Spleens used to produce the blood cells- splenomegaly- will present with symptoms at this point early satiety, abdominal pain, discomfort, constitutional symptoms. Can develop from polycythaemia Vera and ET.

Question 59

Myelofibrosis management:

Answer 59

Low risk- hydroxycarbamide, CVS risk and anti platelets. Higher risk- JAK2 inhibitor. If not effective then a bone marrow transplant is used.

Question 60

ITP:

Answer 60

Immune system attacks platelets. | Can be caused by infections or cancers.

Question 61

Diagnosis of ITP:

Answer 61

``` Not anameic and normal wbc All of sudden low platelet Diagnosis of exclusion Exclude anaemia caused by iron deficiency, B12, folate deficiency. Viral infection; EBV, hepatitis, HIV Medication side effects ```

Question 62

ITP management:

Answer 62

Need treating at a count of 10. Start on steroids roughly 1mg/kg of prednisolone or 40mg dexamethasone. Give IV immunoglobulin for acute action, lasting 4-6 weeks. After that use TPO- thrombopoeitin.

Question 63

ITP prognosis:

Answer 63

Gets control but can recur again. | In children less likely to recur.

Question 64

Sickle cell anaemia:

Answer 64

Abnormal shape of RBC Get stuck in capillaries and adhere to one another in cell walls. Sickle syndrome;painful crisis. Increase IHD, stroke, retinopathy, spleen-get microinfarcts, sickling sequestion- pooling in the spleen, kidney- CKD, liver, reproductive organs.

Question 65

Painful crisis:

Answer 65

Single point mutation- notice in 6 months since babies born with HbF. Normally in sickle cell these cells are normal, but when under oxidative stress there’s a change in sickling.

Question 66

Triggers of painful crisis:

Answer 66

``` Cold Stress Infection Pregnancy Accidents Trauma Surgery Any situation which can cause stress ```

Question 67

Management of painful crisis:

Answer 67

``` Pain relief- Morphine (0.1mg/kg and reassess every 20-30 mins) usually but ask pt which they usually take. Ensure they breathe deeply without feeling the pain of poor rib perfusion. Paracetamol and ibuprofen also. Give O2 regardless of high sats LMWH IV Fluids 3-4L/day ``` If life threatening and these not working then give blood transfusion- sickle negative blood. If very severe then an exchange transfusion would be more preferred, replacing 4-6 units on average.

Question 68

Sickle cell imvestigations

Answer 68

``` Blood films FBC U+Es Reticulocytes Bilirubin LDH Haemoglobinopathy screen/ hameoglobin electrophoresis. CXR- severe sickling will look like consolidation in the lungs ```

Question 69

Long term sickle management:

Answer 69

Hydroxycarbamide- suppresses HbS production, therefore make more S. every few weeks transfusion Or regular exchange programme if had life threatening or have severe sickle episodes.