Hematological Flashcards
Physiology of Blood
Transportation - transports oxygen from lungs to cells and carbon dioxide from cells to lungs
Regulation - homeostasis of all body fluids
Protection - blood can clot, which protects against excessive blood loss
Components of blood
Blood plasma and formed elements
Types of blood
Red - contain haemoglobin to carry oxygen
Platelets - assists in clotting
White blood cells - fights infections, disease and foreign bodies 2 main types - neutrophils and lymphocytes
WBC Function
Monocytes - in blood are mobile and phagocytic, others become macrophages
Lymphocytes - t cell responsible for immunity and B cell with antibody production
Granulocytes - neutrophils protect against foreign materials
Hematological malignancies
Leukaemia’s
Multiple Myeloma
Polycythaemia Rubra Vera
Leukaemia types
ALL - Acute lymphoblastic leukaemia (common in children)
AML - Acute Myeloid leukaemia (mainly adults but can occur in children and adolescents)
CLL - Chronic lymphocytic leukaemia (affects adults)
CML - Chronic myeloid leukaemia (can occur at any age but uncommon below age of 20)
Leukemia and RT
Treating leukaemia that has spread to CNS
Or to the testicles
to treat symptoms caused when swollen internal organs, such as the spleen, press on other organs
May be used before stem cell transplant
Used to relieve bone pain
Treatment for Leukemia depends on
the stage of the disease • the location of the cancer • the severity of symptoms
Standard treatment for acute leukaemia
• Remission induction (3-8 weeks) - no abnormal leukaemic cells
• Consolidation (Intensification of treatment to kill resistance cells, can last 6-9months)
• Maintenance (continuing treatment) - low dose treatment
Disease Classification
Classification based on age, white cell count and cryogenetics of the leukaemia cells
Standard risk - majority of ALL patients
High Risk - all adolescents and younger children with higher leukocyte counts at presentation
Very High Risk - 1-2% with B cell
Special risk patients - Philadelphia chromosome or slow response to induction treatment
ALL Epidemiology and cause
Bone marrow makes too many lymphocytes, gets worse quickly
40% occurs between 2-5 years
Male/female 1:1
Less common than AML
ALL Aetiology
Down syndrome
Environmental agents - viruses
Radiation exposure
ALL Signs and symptoms adults
Peripheral lymphadenopathy
Splenomegaly
Liver palpable
Bone marrow failure - infection due to leucopoenia, bruising and bleeding
Petechiae (flat, pinpoint spots under skin caused by bleeding)
Fever
Shortness of breath
Loss of appetite or weight loss
ALL signs and symptoms Children
oral and pharyngeal ulceration, anaemia, infection, bone pain, few weeks of malaise, fever , haemorrhages in eye, lymph node enlargement, usually pale, bones tender. Meningeal involvement if: headache, stiff neck, vomitting
Adverse prognostic features in childhood ALL
Adverse cytogenic markers, CNS disease, early marrow relapse, testicular relapse, t-cell phenotype, philadelphia chromosome
Above 12yrs, prognosis worse (35% in adults) and 70% in children
Total white cell count - more than 20000 poorer prognosis
Diagnosis for ALL
Physical exam and patient history
Full blood count
Peripheral blood smear
Cytogenic analysis
Erythrocyte sedimentation rate
Immunophenotyping
Liver function
Radiography
Bone marrow biopsy and aspiration
ALL Clinical Management - children
Curative
Multidrug therapy
CNS targeted treatment - common as chemo cannot enter this area due to barrier
Remission Induction - Vincristine, Doxorubicin
Consolidation - Methotrxate - drugs are myelosuppressive
Maintenance - Methotraxate - 2 years, any lower -> increased relapse
87% survival at 5 years
CNS Prophylaxis - intrathecal methotrexate, cranial irradiation
ALL treatment Side Effects
Low neutrophil and platelet count - infections, bleeding
Bone marrow suppression
Hair loss
Kidney damage - increase fluid intake
ALL RT options and dose
Cranial Irradiation
Opposing lateral fields
18Gy in 8-10#
More recently 12Gy
Testicular relapse
24-26Gy in 12-13#
Child in frog-leg position with soles of the feet touching
ALL Relapse
20-25% will relapse
High risk disease -> higher rate of relapse
Relapsed ALL more resistant to treatment than original disease -> leukaemic cells become drug resistant
ALL Relapse Treatment
Repeat remission induction programme
Increased intensity
ALL Adult clinical management
Remission Induction - more intense to children
Consolidation
Maintenance - testicular relapse not common, cranial irradiation not given
ALL Prognostic factors for Adults
Age over 60 years
Late achievement of complete response
B-cell ALL
Philadelphia chromosome
AML epidemology
Rare- accounts for 0.8% of all tumpours in australia
Men slightly higher incidence
More common in adults over age of 60
3.7 in 100,000 in australia don’t survive
AML Aetiology
Damage to one or more of the genes that normally control blood development
Increased incidence in population exposed to radiation after hiroshima and nagasaki
May occur after exposure to chemicals such as formaldehyde
Downs syndrome, myelodysplastic syndrome
Radiation
AML Signs and symptoms
Anaemia, low platelet count - causing bruising and bleeding, low white cell count - persistent infection, fever because of a lack of white blood cells
Aching joints and bones, unusual bleeding - caused by a reduction in the number of platelets
Feeling generally unwell and run down - this may be caused by anaemia or repeated infections
AML Investigations
Full blood count
Biochemistry - checking abnormalities in liver function
Chromosome analysis - bone marrow sample
Radiograph
AML prognosis
Not as good for ALL
Approx 40% of all patients are cured
Increased by successful transplantation to 50%
AML Clinical Management
Remission Induction - Intensive supportive care, Danorubicin
Maintenance therapy - drugs for remission with other agents - etoposide
Consider allogeneic or autologus transplant as late intensification in CR
AML prognostic factors
Age over 60 years
High WBC
Poor performance status
Patients who developed AML after myelodysplastic syndrome
CML cause
Myeloid cells found in bone marrow and circulating blood
Characterised by excess granulocytes
Progress slowly in chronic phase (4-6years), then rapid (3-9 months)
Difficult to detect in early stage
Only cure is stem cell transplant
CML Epidemiology
249 people diagnosed each year in australia (very rare)
Can occur at any age but is more common in adult over 50
Slightly higher in males
CML Aetiology and prognosis
Not known
90% of cases characterised by philadelphia chromosome
Exposure to radiation
Median survival = 4 years
CML Signs and symptoms
Massive splenomegaly
Tiredness and pale skin due to anaemia
Excessive bleeding or bruising at various sites
Petechiae
Periods heavier
Itching
Abdominal distension
Lymphadenopathy
Thrombocytopenia
Bone pain
Fever
Very high white cell count
Weight loss
CML investigations
Blood count - increased number of basophils
Bone marrow biopsy
Ultrasound for hepatomegaly and splenomegaly
Bone marrow sampling
Philadelphia chromosome test
CML Phases
Chronic phase - stable, most people diagnosed in this phase
Accelerated phase - the disease is developing more quickly
Blast phase - much of the bone marrow has been replaced by many immature cells
Phase is determined by number of blast cells in bone marrow and severity of symptom
CML Stages
Relapsed chronix myeloid leukaemia
Complete remission
Molecular remission
CLL
Very similar characteristics to Non-hodgkins lymphoma
Results from injury to DNA of single cell in bone marrow - uncontrolled growth of B-lymphocytic cells in blood
Leukaemic cells that accumulate in marrow do not impede blood production as much as ALL
CLL Epidemiology
Accounts for 0.8% of all cancers diagnosed
Almost 80% of all new cases occur in people over the age of 60 years
Commonly in men
CLL Aetiology
No known factors
Family history
Not associated with radiation exposure
CLL Signs and symptoms
Peripheral lymphadenopathy
Splenomegaly
Hepatomegaly
Anaemia
Tiredness
Shortness of breath on physical activity
Sweats, fever, weightloss
Recurrent infections
CLL Diagnosis
FBC, Bone marrow biopsy
CLL Prognosis
Remission is usually achieved easily but cure is rare
Patients can live many years in remission
Median survival = 8 years
CLL Clinical Management
No cure, Early stage - watch and wait, Late stages - chemo regimes
Chlorambucil
Prednisolone
Hairy Cell Leukemia symptoms
Tiredness, weight loss, infections, anaemia, frequent infections, enlarged spleen
Multiple Myeloma
B-lymphocyte neoplasm
Results in large numbers of immature plasma cells - that infiltrate the bone marow and can be found in blood
Multiple Myeloma Epidemiology
- Uncommon under 50s
- Twice as common in males
- Annual incidence is 4/100000
- Increased rates of incidence
- Carriers of BRCA1 and BRCA2
Family clusters
Multiple Myeloma aetiology
Radiation exposure
Multiple myeloma signs and symptoms
Acute back pain, weakness, anorexia and weight loss, bacterial infections, bone lesions, hypercalcemia, renal failure
Multiple myeloma investigations
FBC, Biochemistry, Urine test, bone marrow biopsy, radiographs and scans
Multiple Myeloma clinical management
Not curable but possible to relieve symptoms
Palliative radiotherapy or chemo
Asymptomatic patients not treated unless disease progressing
RT- Cord Compression, bone pain, whole brain
Polycythaemia Rubra Vera
Uncommon bone marrow disease
Most common in men between 50-65 years of age
Myelo-proliferation - over production of red blood cells
Can also effect other blood cell types
Polycythaemia Rubra Vera signs and symptoms
Increased peripheral cell volume - leading to marrow exhaustion
Headaches
Dizziness
Tinnitus
Tiredness
Visual disturbances
Cyanosis
Pruritus
Palpable spleen (75%)
Hepatomegaly (30%)
Polycythaemia Rubra Vera prognosis
3yr 50% survival after diagnosis in absence of treatment
10 yr 50% survival with treatment
Patient eventually dies of marrow failure, thrombosis, haemorrhage or heart failure
Treatment of Primary disease
Chemotherapy given with curative intent - melphalanor Cyclophosphamide
Younger/fitter patient given more intensive chemo
Majority carried out using patient’s own stem cells
Chemo Delivery
Hickman line - decreases needle punctures needed for IV medication
Can be used for longer
Port-a-catheter - implanted beneath the skin, cannot be pulled, less infection
Bone Marrow Transplantation
Hematopoietic Stem Cell Transplant
2 types -
autologous - patient receives own stem cells
allogeneic - patient receives cells from a relative or matched donor
TBI dose
Total body irradiation
Dose fractionation: 14.4Gy in 8# over 4 days
12 Gy in 6# over 3 days
Patient Care
- Mouth sores
- bleeding
- Infection
- Infertility
- Pneumonitis
- Relapse
- Second cancer
- Diarrhea
- Hair loss
Post transplant lymphoprliferative disorder (PTLD)
classification of AML
using FAB
TBI
effective as biological effect is equally distributed
requires multi-disciplinary team due to accurate calculation of dose
Limited to public hospitals
Patient positioned upright, several m from source, with custom blocks for shielding
Using opposed, parallel, horizontal field setup
Can be half sitted - due to long treatment time, if the patient is tall
Can also be lying on the side, arms by side to reduce dose to lung
Simulated in treatment position
Need to measure - patient height, separation, SSN, head, umbilicus, thighs, ankle
Shielding for lung
Prescribed to umbiicus or midline
gantry 90 degrees, collimator is 40x40
Plastic screen helps allow dose to skin
High scatter
CT based 3DCRT and IMRT, helical tomography
SAD to be considered during placement of lung shielding
Head compensator - layers of lead, harden photon beam and increase scatter dose
Compensators - to account for different separations of different body parts
