Lecture 11: Acute Leukaemia Flashcards
What do blood samples of people with leukemia look like?
Pus without sign of infection
Leukaemias result from _accumulation of immature white blood cells i_n bone marrow. These abnormal leukaemic cells expand and replace normal bone marrow elements, and spillover into the blood.
This resulting in bone marrow failure (anaemia, thrombocytopenia and neutropenia), raised white cell count and sometimes infiltration of other organs.
What does Leukemia result in?
Leukaemias result from accumulation of immature white blood cells in bone marrow.
These abnormal leukaemic cells expand and replace normal bone marrow (hematopoesis) elements, and the immature white blood (cells from the myloid or lymphoid lineage- acute myeloid leukemia vs acute lymphoblastic leukemia) cells spillover into the blood.
This resulting in bone marrow failure (anaemia, thrombocytopenia and neutropenia), r_aised white cell count_ and sometimes i_nfiltration of other organs._
Leukaemias result from ______________________________in _____________
This resulting in ______________, ________________ and sometimes _______________
Leukaemias result from accumulation of immature white blood cells in bone marrow.
These abnormal leukaemic cells expand and replace normal bone marrow elements, and spillover into the blood.
This resulting in bone marrow failure (anaemia, thrombocytopenia and neutropenia), raised white cell count and sometimes infiltration of other organs.
What are the different types of Blood and Marrow Cancers? (4)
-
Leukaemias
- Leukemia is cancer of the body’s blood-forming tissues, including the bone marrow and the lymphatic system.
-
Myeloproliferative neoplasms,
- e.g. polycythaemia.
- Mutations in the hematopoetic stem cells that drive proliferation, but normal differentiation
- They have high Haemglobin levels (polycythemia) (Clinical scenario Blood 06)
- Myeloproliferative Neoplasms (MPNs) are blood cancers that occur when the body makes too many white or red blood cells, or platelets.
- e.g. polycythaemia.
-
Lymphomas,
- e.g. Hodgkin lymphoma
- Large lymph nodes
- Lymphoma originates in developing B-lymphocytes and T-lymphocytes, which have undergone a malignant (cancerous) change.
- e.g. Hodgkin lymphoma
-
Myeloma
- Plasma cell disorders,
- Cancer of plasma cells
- Present with Bome Marrow failure and have lytic bone lesions because of production of cytokines
What are the 2 types of Acute Leukaemia?
1) Acute Myeloid Leukaemia (AML)
2) Acute Lymphoblastic Leukaemia (ALL)
What are the predisposing factors to Leukaemia?
Predisposing Factors
- Congenital/inherited risk facrors (occasional twin cases)
- Viral infection (HTLVI associated with T cell leukaemia or lymphoma in Japan)
- Radiation (increased leukaemia post-A bomb, Chernobyl)
- Chemical and DNA damaging drugs (alkylating agents)
- Downs and other rare congenital disorders (associated with increased risk of leukaemia)
Describe 1 acquired cytogenic and molecular change that results in leukemia
Most cases are not able to identify an environmental or congenital risk factors, but acquired cytogenetic and molecular changes are found in most leukaemias (prognostic significance, therapeutic potential, implications for pathogenesis). Leukaemic transformation of normal haemopoietic cells reflects an acquired somatic cell genetic event:
- Leukaemias are frequently associated with acquired chromosomal change, e.g. Philadelphia chromosome translocation(9;22) in chronic myeloid leukaemia (CML) and some cases of acute leukaemia
- Leukaemias following treatment of other malignancies with alkylating agents and radiotherapy (damage DNA).
Current evidence suggests genetic changes result in activation of dominant acting cancer genes (oncogenes), and loss of tumour suppressor genes. These acquired mutations result in increased cell proliferation; impaired cell differentiation and maturation.
Imatinib stops phosphorylation of tyrosine and these cells die by apoptosis.
What is currently a drug therapy for Chronic Myeloid Leukemia/
- Leukaemias are frequently associated with acquired chromosomal change, e.g. Philadelphia chromosome translocation(9;22) in chronic myeloid leukaemia (CML) and some cases of acute leukaemia
- Activate proliferative gene
- Leukaemias following treatment of other malignancies with alkylating agents and radiotherapy (damage DNA).
Imatinib stops phosphorylation of tyrosine and these cells die by apoptosis.
What are the 2 classifications of Leukemia?
Name the subcategories
Acute Leukaemia
- Acute lymphoblastic leukaemia (ALL) have subtypes based on phenotype (B or T cell). It is more common in childhood (85%).
- Acute myeloblastic (myeloid) leukaemia (AML) have several subtypes based on molecular genetics, phenotype and morphology. It is more common in adults (85%).
Clinical features and mortality of acute leukaemia arises from bone marrow failure and to a lesser extent organ infiltration.
- Bone marrow failure include anaemia (pale, lethargic); neutropenia (fever, infections, wounds slow to heal); thrombocytopenia (bruising, bleeding)
- Organ infliltration include bone marrow (tender bones); hepatomogaly, splenomegaly; lymphadenopathy (ALL); other sites such as gums, skin, CNS, thymus.
Chronic Leukaemia
- Chronic myeloid leukaemia (CML) is really a myeloproliferative disorder (e.g. philadelphia chromosome translocation)
- Chronic lymphocytic leukaemia (CLL) is one of chronic lymphoproliferative disorders and related to lymphomas.
What are the clinical symptoms of acute lekaemia?
Signs and symptoms at presentation is due to bone marrow failure
1) Anaemia- fatigue, dyspnoea, chest pain
2) Neutropenia- infection, wounds, slow to heal
4) Thrombocytopenia (low platlet count)- brusing and bleeding
Other symptoms and signs due to organ infiltration
5) Bone marrow- bone pain
6) Enlarged Liver, Spleen, Lymph nodes
7) Other sites e.g. gum hypertrophy
How do you diagnose Leukaemia?
Full Blood Count
- Normochromic anaemia (low Hb)
- White cell count increased due to circulating blasts (leukaemic cells in peripheral blood), occasionally low neutrophils with few blasts in blood
- Severe thrombocytopenia (platelets often less than 20x109/L (150-400))
But to diagnose, you need….
Bone Marrow Biopsy; Aspirate; Trephine
-
Hypercellular,
- >20% leukaemic blasts in bone marrow (myeloid or lymphoid) (usually 80-90%)
Specialised Testing (Differentiation of ALL and AML)- Bone marrow biopsy
Additional investigations performed on leukaemic blasts from peripheral blood and bone marrow help to separate two major types of acute leukaemia and to subtype these further as follows:
- Morphology
- Cytochemistry
- Immunophenotype (using labelled antibodies to myeloid and lymphoid antigens)
- Cytogenetics (chromosomes)
- Cytogenetic risk groups in AML. Different chormosomal abnormalities put different patients into different prognostic groups.
- DNA analysis (molecular studies) (e.g. immunoglobulin gene rearrangement).
What would we expect to see in a full blood count in someone with leukaemia?
Full Blood Count
- Normochromic anaemia (low Hb)
- White cell count increased due to circulating blasts (leukaemic cells in peripheral blood), low neutrophils with few blasts in blood
- Severe thrombocytopenia (platelets often less than 20x109/L (150-400))
What testing can you do to differentiate between ALL and AML?
Specialised Testing (Differentiation of ALL and AML)
Additional investigations performed on leukaemic blasts from peripheral blood and bone marrow help to _separate two major types of acute leukaemi_a and to subtype these further as follows:
- Morphology
- Cytochemistry
- Immunophenotype (using labelled antibodies to myeloid and lymphoid antigens)
- Cytogenetics (chromosomes)
- Cytogenetic risk groups in AML. Different chormosomal abnormalities put different patients into different prognostic groups.
- DNA analysis (molecular studies) (e.g. immunoglobulin gene rearrangement).
Why do we undergo cytogenetic studies from biopsies in patients with AML?
Cytogenetics (chromosomes)
- Cytogenetic risk groups in AML. Different chormosomal abnormalities put different patients into different prognostic groups.
What is the management strategy for people with Acute Leukaemia?
Management and Therapy of Acute Leukaemia
Acute leukaemias are now potentially curable in a significant number of patients. Treatment is usually undertaken in s_pecialised units (big cities)_ and includes supportive care and specific anti-leukaemia (cytotoxic) therapy.
1) General and Supportive Care
Bone marrow failure management
-
Intensive transfusion support
- Anaemia (r_ed cell transfusion)_
- Bleeding (platelets transfusion, often given prophylactically)
-
Management of Infection
- (ID and lab support, empiric treatment of fever with antibiotics)
- Usually don’t transfuse white cells
- (ID and lab support, empiric treatment of fever with antibiotics)
-
Vascular access
- Tunneled venous cathers
- (use of indwelling central vein catheters to avoid repeated venipuncture)
- Social and family supports
2) Chemotherapy for Acute Leukaemia (Cytotoxic Drug Therapy)
-
Induction therapy
- (to induce remission)
-
Consolidation
- (when they’re in remission but we know there are submicroscopic cells- to mop up residual leukaemia cells)
-
Maintenance therapy
- (in ALL only) (to keep patient in remission)
3) Haematopoietic Stem Cell Transplantation (HSCT)
Autologous (own stem cells taken in remission) or _allogeneic (_matched siblings or undrelated donor) transplatation may be considered in patients <40-50 years old with AML/ALL in 1st or later remission.
- Autologous is own stem cells taken in remission
- Allogeneic is matched sibling or unrelated donor
Stem cells is from bone marrow, peripheral blood or cord blood
