Haem practical rev 3

What is the diagnosis when blasts predominate on a peripheral blood film?

Acute leukaemia.

Which investigations are required to diagnose acute leukaemia?

Bone marrow aspirate, cytogenetics, cytochemistry (MPO, Sudan Black, PAS), and immunophenotyping.

Why is immunophenotyping performed in acute leukaemia?

To distinguish AML from ALL.

Which cytochemical stain is commonly positive in AML?

Myeloperoxidase (MPO).

Which additional cytochemical stain is useful in AML?

Sudan Black B.

Which cytochemical stain is useful in ALL?

Periodic Acid-Schiff (PAS).

What is the first phase of treatment for acute leukaemia?

Induction chemotherapy.

What is the goal of induction chemotherapy?

Achieve complete remission.

What follows induction chemotherapy?

Consolidation therapy.

Why is consolidation therapy given?

To eliminate residual leukaemic cells.

Which type of acute leukaemia routinely requires CNS prophylaxis?

Acute lymphoblastic leukaemia (ALL).

Which type of acute leukaemia has a maintenance phase?

ALL.

Does AML routinely require maintenance therapy?

No.

What supportive care is given during acute leukaemia treatment?

Blood transfusion, infection prophylaxis/treatment, hydration, allopurinol, and correction of coagulopathy.

When is allogeneic stem cell transplantation considered in acute leukaemia?

High-risk disease or relapse.

What are the phases of chronic myeloid leukaemia (CML)?

Chronic phase, accelerated phase, and blast phase.

What blast percentage defines the chronic phase of CML?

Less than 10%.

What blast percentage defines the accelerated phase of CML?

10–19%.

What blast percentage defines blast crisis?

20% or more.

Which chromosomal abnormality characterizes CML?

Philadelphia chromosome t(9;22)(q34;q11).

What fusion gene is produced by the Philadelphia chromosome?

BCR-ABL1.

Which test is the molecular gold standard for diagnosing CML?

RT-PCR for the BCR-ABL1 transcript.

Which cytogenetic tests detect the Philadelphia chromosome?

Karyotyping and FISH.

What happens to the leucocyte alkaline phosphatase (LAP) score in CML?

It is low.

What is the first-line treatment for CML?

Tyrosine kinase inhibitors (TKIs).

Which TKI is commonly used first-line in CML?

Imatinib.

Name two second-generation TKIs used for CML.

Dasatinib and nilotinib.

Which TKI is used for resistant or T315I-mutated CML?

Ponatinib.

Which drug may be used during pregnancy for CML?

Interferon-alpha.

When is stem cell transplantation indicated in CML?

TKI-resistant disease or blast-phase disease.

What is seen on a peripheral blood film in CML?

Granulocytic cells at multiple stages of maturation.

Which maturation stages are seen in CML?

Myelocytes, metamyelocytes, band forms, and segmented neutrophils.

What blood film feature distinguishes CML from reactive leucocytosis?

Complete myeloid maturation spectrum.

How does the LAP score differ between CML and a reactive leukaemoid reaction?

Low in CML and high in a reactive leukaemoid reaction.

Which white cell is characteristically increased in CML but uncommon in reactive leucocytosis?

Basophils.

Which confirmatory tests diagnose CML?

Cytogenetics/FISH for Philadelphia chromosome or RT-PCR for BCR-ABL1.

What determines the phase of CML?

Blast percentage in blood or bone marrow.

How is chronic lymphocytic leukaemia (CLL) diagnosed?

Persistent absolute lymphocytosis >5 × 10⁹/L for over 3 months, peripheral blood film, and flow cytometry.

What is the minimum duration of lymphocytosis required to diagnose CLL?

More than 3 months.

What peripheral blood film findings are seen in CLL?

Mature small lymphocytes and smudge cells.

Which markers are positive in CLL?

CD5, CD19, CD20, and CD23.

How is surface immunoglobulin expressed in CLL?

Weakly.

Which marrow infiltration pattern has a better prognosis in CLL?

Nodular/interstitial infiltration.

Which marrow infiltration pattern indicates a worse prognosis in CLL?

Diffuse infiltration.

Which BTK inhibitors are used in CLL?

Ibrutinib and acalabrutinib.

Which BCL-2 inhibitor is commonly used in CLL?

Venetoclax.

Which anti-CD20 monoclonal antibody is commonly combined with venetoclax?

Rituximab.

Which purine analogue is used in CLL?

Fludarabine.

Which pyrimidine analogue is used in CLL?

Cytarabine.

What does a CLL marrow show?

Dense lymphocytic infiltration replacing normal haemopoietic tissue.

What is a smudge cell?

An artefactually disrupted fragile lymphocyte on a blood film.

Why are smudge cells common in CLL?

CLL lymphocytes are mechanically fragile.

What does diffuse marrow infiltration indicate in CLL?

Advanced disease and poorer prognosis.

How is ALL classified morphologically?

FAB L1, L2, and L3 subtypes.

Which FAB subtype is the commonest in children?

L1.

Describe FAB L1 ALL.

Small, monomorphic lymphoblasts with scant cytoplasm and inconspicuous nucleoli.

Describe FAB L2 ALL.

Larger heterogeneous lymphoblasts with abundant cytoplasm and prominent nucleoli.

Which FAB subtype is more common in adults?

L2.

Describe FAB L3 ALL.

Large uniform blasts with deeply basophilic vacuolated cytoplasm.

Which ALL subtype resembles Burkitt lymphoma?

FAB L3.

Which factors determine ALL risk stratification?

Age, WBC count, immunophenotype, cytogenetics, and CNS/testicular involvement.

Which cytogenetic abnormality makes ALL high-risk?

Philadelphia chromosome positivity.

Which sanctuary sites are important in ALL?

CNS and testes.

What drugs are used during induction therapy for ALL?

Vincristine, corticosteroids, L-asparaginase, with or without an anthracycline.

What drugs are commonly used during consolidation therapy in ALL?

Methotrexate, cyclophosphamide, L-asparaginase, and cytarabine.

What drug is commonly used for CNS prophylaxis in ALL?

Intrathecal methotrexate.

What drugs are commonly used during maintenance therapy in ALL?

Weekly methotrexate with monthly vincristine and corticosteroids.

How long is maintenance therapy for ALL usually continued?

2–3 years.

Describe the morphology of FAB L3 ALL.

Large uniform blasts with deeply basophilic cytoplasm, cytoplasmic vacuoles, coarse chromatin, and visible nucleoli.

What is the diagnosis of large vacuolated basophilic blasts?

Acute lymphoblastic leukaemia, FAB L3 subtype.

Which immunophenotype confirms FAB L3 ALL?

Surface immunoglobulin positivity with CD19, CD20, and CD10 positivity.

Which immunoglobulin finding distinguishes L3 ALL from L1/L2 ALL?

Surface immunoglobulin is present in L3 but absent in L1/L2.

Which chromosomal translocation characterizes FAB L3 ALL?

t(8;14)(q24;q32).

Which oncogene is activated by t(8;14)?

MYC.

Why is recognizing FAB L3 morphology important?

It requires Burkitt lymphoma-type chemotherapy rather than standard ALL treatment.

Why is tumour lysis syndrome particularly common in FAB L3 ALL?

Because of its extremely high proliferative rate.

What is the characteristic microscopic appearance of Burkitt lymphoma?

Starry-sky appearance.

What produces the starry-sky appearance?

Pale macrophages containing apoptotic tumour debris scattered among densely packed lymphoma cells.

What are the two major types of Burkitt lymphoma?

Sporadic and endemic.

Where is sporadic Burkitt lymphoma commonly found?

Worldwide.

Is sporadic Burkitt lymphoma associated with malaria?

No.

What is the common presentation of sporadic Burkitt lymphoma?

An abdominal mass.

Where is endemic Burkitt lymphoma most common?

Equatorial Africa.

Which virus is strongly associated with endemic Burkitt lymphoma?

Epstein-Barr virus (EBV).

Which parasitic disease is associated with endemic Burkitt lymphoma?

Malaria.

What is the classical presentation of endemic Burkitt lymphoma?

Jaw or facial swelling.

What is the hallmark cytogenetic abnormality of Burkitt lymphoma?

MYC translocation involving chromosome 8.

What is the commonest translocation in Burkitt lymphoma?

t(8;14)(q24;q32).

Which gene is involved in t(8;14)?

Immunoglobulin heavy-chain (IgH) gene on chromosome 14.

What are the less common MYC translocations in Burkitt lymphoma?

t(2;8) and t(8;22).

Which immunoglobulin chain is involved in t(2;8)?

Kappa light chain.

Which immunoglobulin chain is involved in t(8;22)?

Lambda light chain.

What is the effect of MYC translocation?

MYC overexpression leading to rapid cell proliferation.

What is the treatment of Burkitt lymphoma?

Short, intensive combination chemotherapy (e.g., CODOX-M/IVAC).

Why are standard lymphoma regimens unsuitable for Burkitt lymphoma?

Because of its extremely high proliferation rate.

Which monoclonal antibody is added in B-cell Burkitt lymphoma?

Rituximab.

Why is CNS prophylaxis routinely given in Burkitt lymphoma?

Because Burkitt lymphoma has a high tendency for CNS involvement.

Which drug is commonly used for CNS prophylaxis?

Intrathecal chemotherapy (e.g., methotrexate).

Why must tumour lysis syndrome prophylaxis be started before treatment?

Because Burkitt lymphoma has a very high tumour burden and rapid cell turnover.