Leukaemia Flashcards
What does leukaemia affect?
The ability to produce normal blood cells
What does leukaemia cause?
The overproduction of abnormal, immature WBC in the bone marrow
What 2 categories do leukaemia’s fall into?
Chronic or acute
What 2 cell type categories do leukaemia’s fall into?
Lymphoblastic or myeloid
What 4 categories can stem cells develop into?
Lymphoid stem cells, myeloid stem cells, erythroblasts and megakaryoblasts
Lymphoid cells become?
WBC Lymphocytes (T and B)
Myeloid cells become?
WBC Monocytes and neutrophils
Erythroblasts become?
RBC
Megakaryoblasts become?
Platelets
What are the 2 acute classifications?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
What are the 2 chronic classifications?
Chronic lymphoblastic leukaemia
Chronic myeloid leukaemia
What is ALL characterised by?
Overproduction of cancerous, immature lymphocytes (lymphoblasts)
What is AML characterised by?
Rapid growth of WBC that accumulate in the bone marrow and affect WBC production
Function of monocytes (myeloid)?
WBC - responds to bacteria, viruses and fungi, produced in the bone marrow and released when infection occurs
Function of lymphocytes (lymphoblastic)?
Many functions.
B - mature in bone marrow
T - mature in thymus
What is chronic leukaemia characterise by?
Build up of abnormal WBC over months or years
What is the peak incidence age of ALL?
0-4
What is the management of ALL?
1 - Induction - 4 week chemo
2 - Consolidation - 4 week chemo
3 - Maintenance - weekly 3 weeks chemo (methotrexate)
4 - 4 cycles chemo + maintenance or stem cell transplant
vincristine, dexamethasone
Pegaspargase - combination therapy
What is the management of AML?
1 - Induction - 4 week chemo
2 - Consolidation - 4 week chemo
*3 - Maintenance - weekly 3 weeks chemo (methotrexate)
*4 - 4 cycles chemo + maintenance or stem cell transplant
cytarabine
What is the management of CLL?
1 - Watch and wait
*2 - Chemo (fast developing disease)
*3 - RT (lymphadenopathy 4gy)
*4 - Surgery or RT (splenomegaly 6-10gy)
*5 - Bone marrow transplant (rare)
What is the management of CML?
1 - Biological therapy (imatinib)
2 - Chemo
*3 - Bone marrow or stem cell transplant
*4 - RT (rarely used - symptom palliation)
Induction chemotherapy purpose?
Clear the blood of leukaemia cells
Reduce the number of blasts in the bone marrow to normal
Consolidation chemotherapy purpose?
Given after induction recovery
Kills remaining (undetectable) leukaemia cells
Maintenance chemotherapy purpose?
Long term low dose
Not used for all leukaemia types - most common for ALL
Name a AML chemo drug
Cytarabine
Name a ALL chemo drug
Vincristine, dexamethasone
What drug is used for maintenance?
Methotrexate
General chemotherapy side effects
Nausea
Alopecia
Cardiotoxicity
Neuropathy
Skin changes
Mouth sores
Taste changes
Infertility/sexual dysfunction
What is Pegaspargase (oncaspar)?
Used as combination therapy for ALL management
Recommended for use in children, young people and adults, diagnosed with untreated, new disease
Pegaspargase (oncaspar) side effects
Nausea/vomiting
Stomach pain
Weakness
Allergic reaction
Mouth pain
Acute pancreatitis (rare)
What are the 2 types of stem cell transplant?
Autologous and allogeneic
What happens in a autologous stem cell transplant?
Stem cells harvested from the patient are given back after conditioning regimen of high dose chemo and/or RT
What happens in a allogenic stem cell transplant?
Same procedure as autologous, however, uses relative, unrelated individual or saved umbilical cord blood
Needs a successful human leukocyte antigens (HLA) test
Preferable as donor cells are non-malignant but hard to match donors
When would you use TBI?
Before stem cell transplant to help reduce chance of transplant rejection or if stem cell transplant has failed
Side effects of TBI?
Nausea, diarrhoea, fatigue, mouth sores, skin changes, immunosuppression
What is often shielded for TBI and why?
Reduce long term issues and even out dose
Infection control
Protective isolation
Room sterilisation
Clean air
Clean food
Purified water
Removal of plants
Hand washing
Sealed room
1 visitor per day
Can lead to psychological issues
What percentage of new cancer diagnoses does CLL account for (2016-2018)?
1%
What is CLL incidence rates strongly related to?
Age
What staging system does CLL use?
The Binet Staging system
How many stages does the CLL Binet staging system have?
3 (Stage A, B and C)
What does CLL Binet staging system Stage A mean?
Fewer than 3 groups of enlarged lymph nodes (lymphadenopathy) and a high white blood cell count
What does CLL Binet staging system Stage B mean?
More than 3 groups of enlarged lymph nodes (lymphadenopathy) and a high white blood count
What does CLL Binet staging system Stage C mean?
Enlarged lymph nodes or spleen, a. high white blood cell count and low red blood and platelet counts
What percentage of new cancer diagnoses does CML account for (2016-2018)?
Less than 1%
What gender are incidence rates lower in CML?
Females
What are the 3 phases of CML?
Chronic, accelerated, blast crisis
How many patients present in the chronic phase?
85%
What is shown in the accelerated phase?
Some signs in blood/bone marrow that patient is moving towards blast crisis
What happens to cells in the blast crisis phase?
Behaves like AML
Rapid progression
Short survival
What does the Philadelphia chromosome cause?
Causes the production of an enzyme called tyrosine kinase (TK) which stimulates the production of leukaemic cells
What is the Philadelphia chromosome treated with?
Treated with TK inhibitors (TKI therapy) such as Glivec
Arsenic Trioxide (Trisenox or ATO)
Long history of use in Chinese medicine
Current use in subtype of AML (acute promylocytic leukaemia)
‘chemo free’ treatment
Minimal side effects
Given over 6 month period
Causes death of leukaemia cells via morphological changes and DNA fragmentation. Arsenic Trioxide also damages or degrades the fusion protein promyelocytic leukemia (PML) - retinoic acid receptor (RAR) alpha
Monoclonal antibodies
Monoclonal antibodies recognise and find specific abnormal proteins on cancer cells
Each monoclonal antibody recognises 1 particular protein
Different cancers have different abnormal proteins, CD20 in CLL
CD20 antigen is a protein found on surface of B-lymphocytes
Drugs include; Rituximab, Obinutuzumab and Ofatumumab
CD52 antigen found on surface of CLL cells and many T-lymphocytes
Alemtuzumab (Campath) targets CD52, used if CLL no longer responding to standard chemo
What is CAR T cell treatment?
Blood taken from patients and separated to get T-cells
The T-cells are then genetically engineered, using a disarmed virus (not going to harm the cell anymore), to produce cell surface receptors, called Chimeric Antigen Receptors (CARs)
These receptors then allow the T cells to recognise and attach to a specific protein or antigen on tumour cells
An antigen found on B-cells is CD19
The CAR s “program” the T-cells to find and destroy cancer cells
CAR T cell therapy used for B-cell ALL patients recurrence or relapse (Kymriah)
How common is leukaemia in the UK overall?
12th most common
How common is leukaemia in UK males?
10th most common
What is the cause of leukaemia?
Unsure of cause!
Certain link to DNA mutations disrupting cell death, differentiation or division process
Many different mutations have been identified
Mutations may be due to carcinogens, radiation or exposure to certain viruses
Downs syndrome. 10-20% increased risk of developing acute leukaemia’s
Krummel cluster, Germany
Seascale cluster, 1955-1983. proven higher incidence of leukaemia near to Sellafield
Chernobyl
East v’s West Germany
Leukaemia symptoms
Fever, chills
Fatigue, weakness
Loss of appetite, weight loss
Night sweats
Bone/joint pain
Abdominal discomfort
Headaches
Shortness of breath
Frequent infections
Easy bruising or bleeding
Petechiae (small red spots under the skin)
Leukaemia signs
Anaemia
Leukopaenia (low white blood cell count)
Thrombocytopenia (low blood platelet count) - bruising or bleeding
Lymphadenopathy (with lymphatic spread)
Hepatomegaly / splenomegaly - abnormal cells in liver or spleen
AML prognostic factors
Age
Treatment induced
Myeloproliferative disorders
CNS involvement
Cytogenics
White blood cell count (>100 unfavourable)
What are cytogenetics?
Investigation of chromosome abnormalities is increasingly valuable for leukaemia diagnosis
Chromosome abnormalities are strongly associated with both AML and ALL
Molecular studies of these abnormalities identified specific genes implicated in leukaemia development
What is complete remission?
No evidence of disease after treatment
Bone marrow contains fewer than 5% blast cells
Blood cell counts within normal limits
No signs or symptoms
“Molecular” complete remission if no leukaemia cells in marrow
What is minimal residual disease?
Sensitive tests (flow cytometry or PCR) find leukaemia in marrow
What is active disease?
Evidence of leukaemia during treatment
Reappearance of disease after treatment (relapse)
More than 5% blast cells in bone marrow
What percentage of deaths does AML account for?
2%
ALL prognostic factors
Gender (males worse)
Age
WBC
Cytogenetics
CNS disease
Response to treatment
What is the Philadelphia chromosome (PH+)?
Translocation of chromosomes 22 and 9
Creates a new “BCR-ABL” gene which produces a new protein
Protein creates an enzyme called tyrosine kinase which stimulates the production of leukaemic cells
Tyrosine Kinase Inhibitors can be used as a treatment
Ph-positive ALL
Approximately 25% of adults with ALL and a small number of children have Philadelphia positive ALL (Ph+)
More strongly associated with CML
Associated with poor prognosis
- More intensive treatment
- Addition of Tyrosine kinase inhibitors (TKIs)
- Addition of Glivec (imatinib) to chemotherapy
- Continuation of Glivec after consolidation
