Leukaemia Flashcards
What is leukaemia?
cancer of a particular line of the stem cells in the bone marrow.
Causes unregulated production of certain types of WBCs
How are leukaemias classified?
depending on how rapidly they progress (slow = chronic or fast = acute) and the cell line that is affected (myeloid or lymphoid)
4 main types of leukaemia
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
Pathophysiology of leukaemia
Form of cancer cells in BM
Genetic mutation in one of the precursor cells in bone marrow leads to excessive production of single type of abnormal white blood cell
What does excessive production of a single type of cell lead to?
suppression of the other cell lines causing underproduction of other cell types. This results in a pancytopenia, which is a combination of low red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia).
Pneumonic for ages of leukaemia
ALL CeLLmates have CoMmon AMbitions
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
Presentation of leukaemia?
Non specific
Fatigue
Fever
Failure to thrive (children)
Pallor due to anaemia
Petechiae and abnormal bruising due to thrombocytopenia
Abnormal bleeding
Lymphadenopathy
Hepatosplenomegaly
One of the key presenting features of leukaemia?
Petechiae
What is petechiae caused by?
Thrombocytopenia (low platelets)
Differential diagnosis for leukaemia? (Due to petechiae) Same for all leukaemias pretty much
Meningococcal septicaemia
Vasculitis
Henoch-Schonlein Purpura (HSP)
Idiopathic Thrombocytopenia Purpura (ITP)
Non-accidental injury
Gold standard initial investigation?
Full blood count
8 hours for patients with suspected leukaemia. Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital.
Main investigation for diagnosing leukaemia?
Bone marrow biopsy - can be used to analyse the cells in the bone marrow
Other tests for leukaemia
Blood film: can be used to look for abnormal cells and inclusions.
Lactate dehydrogenase (LDH): is a blood test that is often raised in leukaemia but is not specific to leukaemia. It can be raised in other cancers and many non-cancerous diseases.
Chest xray may show infection or mediastinal lymphadenopathy.
Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma.
Lumbar puncture may be used if there is central nervous system involvement.
CT, MRI and PET scans can be used for staging and assessing for lymphoma and other tumours.
Bone marrow aspiration
involves taking a liquid sample full of cells from within the bone marrow.
Bone marrow trephine
Involves taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure.
Bone marrow biopsy
taken from the iliac crest. It involves a local anaesthetic and a specialist needle. Samples from bone marrow aspiration can be examined straight away however a trephine sample requires a few days of preparation.
Acute Lymphoblastic Leukaemia
Malignant change in one of the lymphocyte precursor cells.
It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes.
Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia.
RFs for ALL
- Previous chemotherapy
- Radiation exposure
- Down syndrome:20-fold increased risk
- Benzene exposure: painters, petroleum, rubber manufacturers
- Family history:
Signs and symptoms of ALL?
lymphadenopathy
Hepatosplenomegaly
Pallor
Fatigue
Loss of appetite
Weight loss
Easy bruising
If philadelphia gene is present prognosis is poor
Prephase treatment for ALL
- 5 - 7 daysof treatment shortly after diagnosis
- Treat withcorticosteroids, with or without an additionalchemotherapyagent
Induction treatment for ALL
- 4 - 8 weektherapy, e.g.corticosteroids,vincristineordoxorubicin(chemotherapy)
- Imatinibcan be used in addition if Philadelphia chromosome-positive
- Intrathecal therapy (administration into CSF) can be used if there is CNS involvement
2nd line treatment for ALL
BM transplant
Consolidation and maintenance therapy for ALL
Consolidation:
- Up to1 yearof high-dosechemotherapy, which is startedaftercomplete remission
Maintenance:
-2yearsofmercaptopurineandmethotrexatetherapy
Most common cancer in children, adults over 45 and down syndrome?
Acute Lymphoblastic Leukaemia
Primary investigations for ALL
FBC
Blood film
BM aspiration + trephine biopsy
Immunophenotyping
Complications secondary to ALL
- Myelosuppression and neutropaenic sepsis:lymphoblasts invade the bone marrow, disrupting function, and may present with pancytopaenia requiring RBC and platelet transfusion.
- Extramedullary involvement:CNS, testicular, and renal involvement
- Infertility: due to lymphoblast invasion
Chronic Lymphocytic Leukaemia
chronic neoplastic proliferation of a single type of a mature lymphocyte, usually B-lymphocytes.
>55 age
Asymptomatic
Can cause: warm autoimmune haemolytic anaemia.
Can transform into: high-grade lymphoma. This is called Richter’s transformation.
Most common in adults
Difference between acute and chronic leukaemias
CLL and CML cells mature partially
Acute dont mature at all
Presentation of chronic lymphocytic leukaemia
- infections
- anaemia
- bleeding
- weight loss
Progressive: - lymphadenopathy
- hepatosplenomegaly
- BM failure
- infection
S + S of CLL
- Lymphadenopathy
- Hepatosplenomegaly: neoplastic cells invade the liver and spleen
-
Pallor
Fatigue
Weight loss
Fever
Investigations for CLL
FBC
Bloodfilm
Immunoglobulins
Genetic analysis
BM biopsy - not necessary for diagnosis
Management of CLL
Early stage disease : Monitor
Active/ advance:
- FCR:fludarabine, cyclophosphamide and rituximab are used in patients with good performance status
- Chlorambucil and rituximab:used in patients with poor performance status
- Other chemotherapeutic agents:tyrosine kinase inhibitors, such as ibrutinib, are considered in those with del(17p)
- Allogenic stem cell transplant:considered in a specific subset of patients with a good performance status
Complications secondary to CLL
- Hypogammaglobulinaemia:dysfunctional neoplastic B cells exhibit impaired immunoglobulin production
-
Autoimmune haemolytic anaemia:occurs in up to 25% of patientsand most typically is of the warm subtype
- The mechanism is thought to involve neoplastic cells inducing normal B cells to release autoantibodies
- Richter transformation:transformation into a non-Hodgkin lymphoma, most commonly a diffuse large B-cell lymphoma.
Blood film of chronic lymphocytic leukaemia
Blood film shows “smear” or “smudge” cells. These occur during the process of preparing the blood film where aged or fragile white blood cells rupture and leave a smudge on the film.
Risk factors of CML
Excess RBC, platelets, WBC production
RFx: M, Philadelphia Chromosome t(9:22) [BCR- ABL Gene]
Radiation exposure
Chronic Myeloid Leukaemia (CML): 3 phases
Chronic phase
Accelerated Phase
Blast phase
CML Chronic phase
chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised white cell count.
CML accelerated phase
occurs where the abnormal blast cells take up a high proportion of the cells in the bone marrow and blood (10-20%).
In the accelerated phase patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
CML blast phase
Follows the accelerated phase and involves an even high proportion of blast cells and blood (>30%). This phase has severe symptoms and pancytopenia. It is often fatal.
What is CML a cancer of?
Cancer of Granulocytes [Basophil/Eosinophil/Neutrophil] proliferate (>90% survival)
Slow onset
Overproduction of Myeloid Progenitor
Signs and symptoms of CML
Splenomegaly, night sweats, fever & high metabolism.
The presence of Philadelphia chromosome is a diagnostic marker
Hyperviscosity
Bone marrow failure
Weight loss
Treatment of CML in chronic or accelerated phase
Tyrosine kinase inhibitors - 1st line - Imutinib
Treatment of CML blast phase
- Tyrosine kinase inhibitorplushigh dose inductionchemotherapy, followed bystem cell transplantation
- Patients may have pancytopaenia requiring blood and platelet transfusion
What is AML
Acute myeloid leukaemia (AML) involves the proliferation of myeloblasts
Most common acute leukemia in adults?
Acute Myeloid Leukaemia
many different types of acute myeloid leukaemia all with slightly different cytogenetic differences and differences in presentation.
RFs for AML
- AGE
- MYELODYSPLASTIC SYNDROMES
- MYELOPROLIFERATIVE NEOPLASMS
- DOWNS SYNDROME
- PREVIOUS CHEMO
Acute promyelocytic leukameia
t(15;17)translocation involves the fusion of retinoic acid receptor (RAR) with promyelocytic protein (PML), blocking maturation of myeloblasts causing promyelocyte accumulation
- Presents in younger patients than other subtypes; average age is 44 years old
- Demonstrates Auer rods
- thrombocytopenia + DIC
- 80 cure rate
Acute monocytic leukaemia (M5):
- Characterised by monoblast accumulation and usually lack Auer rods
- Results in gum infiltration
What is acute myeloid leukaemia caused by?
immature myeloblast proliferation; incidence increases w/ age – accounts for 10-15% of childhood leukaemias – 60% of which are cured.
Signs and symptoms of AML
BM failure [anaemia, leucopenia (decreased WBC), thrombocytopenia (decreased platelets)]
fatigue,
headaches,
tachycardia,
infections,
gum bleeds,
rash,
purpura [blood going into tissues under skin]
Presentation of acute myeloid leukaemia ?
can present at any age but normally presents from middle age onwards.
It can be the result of a transformation from a myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis.
Bone Marrow Failure: Neutropenia, Anaemia, Thrombocytopenia
Tissue Infiltration:
*Swollen Gums
*Splenomegaly
Blood film of AML
will show a high proportion of blast cells. These blast cells can have rods inside their cytoplasm that are named Auer rods.
Management of Leukaemia
Treatment will be coordinated by an oncology multi-disciplinary team
Primarily treated with chemotherapy and steroids.
Other therapies include:
Radiotherapy
Bone marrow transplant
Surgery
Chemotherapy complications
Failure
Stunted growth and development in children
Infections due to immunodeficiency
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity
Tumour lysis syndrome
Induction treatment for AML
- Chemotherapy: combination ofcytarabineand ananthracycline, such as daunorubicin
- All-trans retinoic acid(ATRA; tretinoin) is added in acute promyelocytic leukaemia (APML). ATRA binds RAR on promyelocytic cells and causes the blasts to mature into neutrophils, which eventually go on to die.
Consolidation treatment for AML
- Furtherchemotherapyis offered
- Patients who are high risk may receivestem cell transplantation
What is the pathophysiology of acute myleoid leukaemia?
Proliferation of myeloblasts
What do myeloblasts become?
A myeloblast is an immature white blood cell. Physiologically, myeloblasts become mature white blood cells calledgranulocytes(neutrophils, eosinophils and basophils)
Diagnosis and investigations for AML?
Auer rods on cytology
