Haematological Malignancies Flashcards
What is Hodgkins Lymphoma?
Abnormal growth and spread of cells of the lymphatic system. Commonly find abnormal numbers of Reed-Sternberg cells.
Hodgkins Lymphoma RF:
Age- 20-40yrs old. >50yrs old.
FHx
Male
EBV
Types of Hodgkins Lymphoma:
Nodular sclerosis Hodgkins Lymphoma
Mixed cellularity Hodgkins Lymphoma
Lymphocyte depleted Hodgkins Lymphoma
Lymphocyte rich Hodgkins Lymphoma
Staging of Hodgkins Lymphoma:
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.
Investigating Hodgkins Lymphoma:
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.
Treating Hodgkins Lymphoma:
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.
What is Non-Hodgkins lymphoma?
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.
Non-Hodgkins lymphoma RF:
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.
Types of Non-Hodgkins lymphoma:
> 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.
Staging Non-Hodgkins lymphoma:
Ann-Arbor staging.
Investigating Non-Hodgkins lymphoma:
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.
Treating Non-Hodgkins lymphoma:
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.
Use of BM aspiration:
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.
Signs/Symptoms of Hodgkins Lymphoma:
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
Signs/Symptoms of Non-Hodgkins Lymphoma:
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
Leukaemia vs Lymphoma:
Leukaemia is restricted to the BM +/- blood.
What is AML?
Cancer of the myeloid progenitor cells. It s rapidly progressing.
Signs/Symptoms of AML:
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
RF for AML:
Increasing age- common in >65yrs Male Exposure to harmful radiation/chemicals Previous chemotherapy Smoking Blood disorders Genetic disorders i.e. Downs syndrome
Diagnosis of AML:
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.
Prognosis of AML:
Dependent on patient health, subtype of AML and age.
Treatment of AML:
Two phases- Remission induction therapy and consolidation therapy.
Phase one includes chemo +/- targeted therapy.
Phase two includes targeted therapy.
What is CML?
Cancer of the myeloid lineage; increasing WBC (except lymphocytes), but normal/below normal RBC/platelets.
Signs/Symptoms of CML:
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
RF for CML:
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!!!
Diagnosis of CML:
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.
Prognosis of CML:
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.
Treatment of CML:
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.
What is ALL?
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.
Signs and symptoms of ALL:
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
RF for ALL:
Previous cancer treatment.
Exposure to radiation.
Genetic disorders; Downs syndrome.
Diagnosis of ALL:
Blood tests
BM
XR, CT scan, USS.
Prognosis of ALL:
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
Treatment of ALL:
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.
What is CLL?
Cancer of the mature lymphoid cells, chronic therefore slowly forming.
Signs/Symptoms of CLL:
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
RF for CLL:
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).
Diagnosis of CLL:
Blood count- look for increase in number of lymphocytes.
Flow cytometry/immunophenotyping to work out the lymphocytes involved.
Analyse genetics using FISH.
Prognosis of CLL:
Stage with CT/PET to then determine the prognosis.
Can go on to cause autoimmune haemolytic anaemia.
Treatment of CLL:
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
What is Myeloma?
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.
Signs/symptoms of Myeloma:
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
RF for Myeloma:
Increasing age Black Male FHx of multiple myeloma Personal Hx of MGUS.
Complications of Myeloma:
Frequent infections
Kidney failure
Anaemia
Bone problems
Diagnosis of Myeloma:
Blood and urine tests looking for paraprotein.
Bone marrow examination including FISH
XR, CT, MRI, PET
Prognosis of Myeloma:
If asymptomatic then watch and wait.
Treatment of Myeloma:
Targeted therapy Chemotherapy Immunotherapy Corticosteroids Radiation therapy BM transplant
SLiM CRAB:
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.
Myeloproliferative disorders:
Polycythaemia vera can develop into MF or AML
Essential thrombocythamaemia can develop into MF or AML
Myelofibrosis
CML
Essential thrombocythaemia
Picked up incidentally
Risk of stroke/MI
Fatigue
ET mutation:
JAK2
CALA
MPL
Need any one of these for a diagnosis with the abnormal blood count.
Thrombocytosis causes:
If not present then think ET.
Bleeding Infection/inflammation Trauma I.e.post surgery Autoimmune Iron deficiency anaemia paradox
Polycythaemia Vera:
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.
ET treatment:
Anti-platelet- used as prophylaxis.
Pay attention to CVS risks.
Hydroxycarbamide- suppresses BM production of normal cell.
Increase Hb
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
Polycythaemia Vera management:
Normal range is 40-50%, aim for 45%. Look at haematocrit to guide treatment. Hydroxycarbamide Anti platelet Venesection
Myelofibrosis:
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.
Myelofibrosis management:
Low risk- hydroxycarbamide, CVS risk and anti platelets.
Higher risk- JAK2 inhibitor.
If not effective then a bone marrow transplant is used.
ITP:
Immune system attacks platelets.
Can be caused by infections or cancers.
Diagnosis of ITP:
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
ITP management:
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.
ITP prognosis:
Gets control but can recur again.
In children less likely to recur.
Sickle cell anaemia:
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.
Painful crisis:
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.
Triggers of painful crisis:
Cold Stress Infection Pregnancy Accidents Trauma Surgery Any situation which can cause stress
Management of painful crisis:
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.
Sickle cell imvestigations
Blood films FBC U+Es Reticulocytes Bilirubin LDH Haemoglobinopathy screen/ hameoglobin electrophoresis. CXR- severe sickling will look like consolidation in the lungs
Long term sickle management:
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.
