PBL 6 – Lymphoma and leukemia

Age bracketing leukemia

0 – 14 15 – 39 (clue: peripheral blood smear will have blasts with Auer rods)40 – 59 > 60

How do you distinguish AML from CML?

Perform a bone marrow aspirate. If <30% of WBCs in the marrow are blasts then you have a chronic CML, whereas if >30% of WBCs are blasts it is acute.

What are more common, NHL or HL?

What is the most common form of NHL?

Ann Arbor classificationI, II, III, IV, E, S, A, B

Hodgkin Non-Hodgkin

Localised or more generalised?Contiguous spread?

Commonly affects Waldeyer ring and mesenteric nodes?Commonly has extra-nodal presentation?

Hodgkin Non-HodgkinOften localised to a single axial group of nodes (cervical, mediastinal, para-arotic)

More frequent involvement of multiple peripheral nodes

Orderly contiguous spread Non-contiguous spread

Rarely mesenteric node and Waldeyer ring involvement

Often Waldeyer ring and mesenteric nodes involvement

Extra-nodal presentation rare Extra-nodal presentation common

Which of the following NHLs are associated with Epstein Bar Virus (EBV)

Diffuse large B-cell lymphoma

Burkett’s lymphoma

Primary CNS lymphoma (common patient’s who also have…?)

Follicular B-cell lymphoma

Structures that may cause lower back pain

Red flags for lower back pain

Which NHL demonstrates the following histology?

What type of NHL demonstrates this pathology? What is it’s prognosis?

What type of NHL demonstrates this pathology? What is it’s prognosis?

Common Lymphoma patternsDiffuse large B cell Follicular B-cell

lymphomaHodgkin’s

Incidence

Age

Node distribution

Diaphragm

Splenomegaly

Bone marrow involvement

Extranodal disease

Treatment

Common Lymphoma patternsDiffuse large B cell Follicular B-cell

lymphomaHodgkin’s

Incidence Around 25% Around 20% Around 11%

Age Incidence increases with age Bimodal; first around 20-30 and second rise after 50

Node distribution Mostly localised mass Usually generalised Often localised; axial distribution

Diaphragm Either side Generalised Most frequently above

Splenomegaly Uncommon Much more common Uncommon

Bone marrow involvement Less common More common Rare

Extranodal disease Frequent Less common Rare

Treatment Curative. R-CHOP Cure is unlikely. Often watch and wait or simple +/- Rituximab. Advanced stage may be given agggressive chemo.

Curative. Early stage radiation, later stage chemotherapy. ABVD

ABVDDoxorubicin (Adriamycin)

Cytotoxic antibiotics (mitomycin), inhibit DNA and RNA synthesis by intercalation of DNA base pairs and prevent DNA repair by inhibiting topoisomerase II, i.e. inserts between DNA base pairsBleomycin

Free radical. Inhibits DNA and to a lesser extent RNA synthesis, produces single and double strand breaks in DNA possibly by free radical formation.

Vinblastin Tubulin-binding drugs (aka Vinca Alkaloids including vincristine, taxol), inhibit mitosis at

metaphase by binding to tubulin and inhibiting its polymerisation into microtubules, preventing spindle formation in dividing cells, i.e. arrest metaphase.

DacarbazineAlkylating agent (cyclophosphomide***, cisplatin), i.e. binds to, and forms cross-linking

between, DNA strands thus interfering with cellular transcription and replication

R-CHOPRituximab

Monoclonal antibody. Anti-CD20 monoclonal antibody that binds to CD20 on B lymphocytes and starts an immune response that lyses normal and malignant B cells. Apoptosis is also induced. Regeneration of normal B lymphocytes occurs.

Cyclophosphamide

Hydroydaunorubicin

Oncovin® (Vincristine)

Prednisolone

Corticosteroids : MOA

1. Lipophilic steroid molecules diffuse through lipid membrane of cells and bind to cytoplasmic, intracellular glucocorticoid receptor

2. Steroid receptors undergo confirmational change which reveals DNA binding site

3. Receptors form dimers which enter nucleus4. Dimers bind to promoter regions of target gene

and cause either induction or repression of gene transcription