ALL Flashcards
ALL commonly affects which age group? [1]
ALL is the most common childhood malignancy
Describe the pathophysiology of ALL
Acute lymphoblastic leukaemia (ALL) affects one of the lymphocyte precursor cells, causing acute proliferation of a single type of lymphocyte, usually B-lymphocytes.
The precursor cell acquire specific chromosomal mutations, which leads to uncontrolled proliferation of lymphoblasts and evasion of immune surveillance
As a result, lymphoblasts infiltrate bone marrow and other organs. which restricts hematopoiesis and leads to bone marrow suppression.
What is the most common cytogenetic feature seen in ALL?
t(4;11)
t(12;21)
t(9;22)
Hypodiploid karyotype
Hypodiploid karyotype
What is the most common cytogenetic feature seen in ALL?
t(4;11)
t(12;21)
t(9;22)
Hypodiploid karyotype
Hypodiploid karyotype
ALL is commonly seen in which patient populations? [3]
Those with chromosomal abnormalities:
- Trisomy 21
- Klinefelter’s syndrome
Fanconi anaemia
Monozygotic twins
The most widely accepted classification system of ALL is the WHO classification.
Describe this classification [3]
- B cell lineage (85% of cases)
- T cell lineage (10-15% cases)
- Rare cases of NK cell lineage (<1% of cases)
Describe the typical presentation of ALL related to marrow failure [4]
Recurrent infections: neutropaenia
Thrombocytopenia:
* Petechiae
* Nose bleeds
* Bruising
Anaemia:
* Fatigue
* Breathlessness
* Angina
* Syncope
Describe the typical presentation of ALL related to tissue infiltration [4]
Lymphadenopathy
- Persistent
- Painless
- Firm & Rubbery
Hepatosplenomegaly
- Can present with anorexia, weight loss or abdomen pain
Bone pain
Mediastinal mass (may result in SVCO)
Testicular enlargement
[]- an uncommon presentation among those being first diagnosed, but more likely among patients with relapsing ALL (10%)
Testicular enlargement ( < 1 %) - an uncommon presentation among those being first diagnosed, but more likely among males with relapsing ALL (10%)
Describe the FBC seen in a patient with ALL [3]
Thrombocytopaenia
Anaemic
WBC: low or high
- Low indicates lymphoblasts present that have not differentiated as recognisable WBC
- High indicates similar enough to WBC to be counted
U&Es; LDH; uric acid high
- Due to metabolic abnormalities
- TLS
T-cell ALL is rarer than the B-cell form. It is said to typically present in which patient population? [1]
Describe two common presenting symptoms [2]
T-cell ALL is rarer than the B-cell form. It is said to typically present in adolescent males with lymphadenopathy or a mediastinal mass.
What investigational tests should you perfom to assess for features of disseminated intravascular coagulation (DIC)? [2]
Coagulation screen and DDIMER
What is the definitve diagnostic test for ALL? [1]
Bone marrow aspiration and biopsy
- Immunophenotyping is used to identify the lineage.
All patients with ALL diagnosis have what investigation performed? [1]
Regardless of symptoms or signs of CNS involvement all children diagnosed with ALL have a lumbar puncture performed to evaluate for CNS involvement, given its association with negative prognosis, and receive prophylactic intrathecal chemotherapy.
Why might a PBS appear normal in a patient with ALL? [1]
Findings on a peripheral smear may be normal if leukaemia is still confined to the bone marrow at the time of presentation.
What is the threshold lymphoblast level in a PBS for ALL diagnosis? [1]
The most commonly accepted threshold for diagnosis is when lymphoblasts occupy >20% of bone marrow.
What specific information does immunophenotyping help provide with regards to ALL? [1]
Through analysis of the surface antigens, this also determines whether the lymphoblasts are of B or T cell lineage.
How would you differentiate ALL from Burkitts lymphoma? [2]
Through histology with the characteristic ‘starry sky’ appearance of highly proliferative cells with basophilic cytoplasm in BL.
Confirmation of Burkitt’s lymphoma involves identification of a mature germinal centre immunophenotype and cytogenetic features specific to Burkitt lymphoma cells
How would you differentiate ALL from AML based off which parts of the body are implicated [2]
ALL has a predisposition for testicular, and CNS involvement
AML has a predisposition to involve skin and gums or other mucous membranes
Confirm AML through the presence of myeloid features and antigens and absence of any lymphoid antigens.
How would you differentiate ALL from aplastic anaemia? [2]
distinguished from ALL by hypocellular bone marrow and the absence of any blast cells.
Describe the overall goals of the different phases of ALL treatment [4]
Pre-treatment & supportive therapy phase
* Treating any infection, metabolic complication and if indicated giving a transfusion to stabilise the patient.
Induction chemotherapy
- goal to eradicate the presence of leukaemic cells to < 5% of blasts and to restore normal haematopoiesis.
Consolidation:
- Prevent the growth of leukaemia from any residual cells (known as a minimal residual disease (MRD)) and to prevent the development of drug resistance, by using numerous agents with multiple mechanisms of action.
Maintenance therapy
- prevent relapse
Desribe how the pre-treatment & supportive therapy phase of ALL is performed [4]
For roughly 5-7 daysL
* Corticosteroids with or without another drug
* Hydration
* Allopurinol
* CNS prophylaxis is given intrathecally
This pre-phase helps reduce the risk of TLS
Desribe how the induction chemotherapyphase of ALL is performed [1]
The selection of chemotherapy is dependent on a multitude of factors including age, Philadelphia chromosome status and the presence of CNS disease. Those with CNS disease require intrathecal chemotherapy and prophylactic therapy may be used in those without to reduce the risk of CNS relapse.
Describe the regime usually used for maintenance therapy fr ALL
daily 6-mercaptopurine and weekly methotrexate
though there is considerable variation.
Describe the regime usually used for consolidation therapy fr ALL
the goal is to prevent the growth of leukaemia from any residual cells (known as a minimal residual disease (MRD)) and to prevent the development of drug resistance, by using numerous agents with multiple mechanisms of action.
For those who don’t achieve a complete remission following induction, termed high-risk cases, ESMO guidelines advise allogeneic haematopoietic cell transplantation leads to better outcomes.
Describe 4 complications of ALL [4]
Tumour lysis syndrome:
- significant metabolic disturbances arising from the rapid breakdown of malignant cells, normally after therapy has been initiated. It should be anticipated and when appropriate prophylaxis may be given with close monitoring and HDU/ITU availability if needed.
Neutropenic sepsis:
- characterised by fever and neutrophils < 0.5 (or expected to fall below 0.5). A medical emergency requiring early identification and management.
SVCO:
- patients may present with features of superior vena cava obstruction (e.g. dyspnea, facial swelling, cough) secondary to a mediastinal mass.
Chemotherapy side-effects:
- depends on the therapy and intensity, can be early (e.g. mucositis, nausea and vomiting, hair loss) or late (e.g. cardiomyopathy, secondary malignancies)
Describe what is meant by L-asparaginase-related coagulopathy [1]
L-asparaginase-related coagulopathy - L-asparaginase is a chemotherapeutic agent which is becoming more widely used. The mechanism of coagulopathy and thrombosis is due to fibrinogen and anti-thrombin 3 depletion.
