Leukaemia and Lymphoma Flashcards
(17 cards)
List the end myeloid and lymphoid cells.
Myeloid:
Basophil, neutrophil, eosinophil, macrophage, platelets
Lymphoid:
NK, T lymphocyte, B lymphocyte
List the major classes of leukaemias and lymphomas.
Leukaemias:
Myeloid: AML or CML
Lymphoid: ALL or CLL
Lymphomas:
■ Many different types, split into 2 main categories:
– Hodgkin
– Non-Hodgkin
*In order, this lecture covers AML, CML, CLL, Hodgkin and non-hodgkin.
List the general investigational findings of leukaemias.
How does this differ from lymphomas?
Leukaemias:
1 ■ Leucocytosis is a prominent feature due to the production of malignant leucocytes and their accumulation in the peripheral blood
2 ■ Bone marrow failure resulting from defective haematopoiesis leads to anaemia,
thrombocytopenia and increased susceptibility to infection
3 ■ In chronic leukaemia, malignant leucocytes may accumulate also in the spleen (CML and CLL), liver or lymph nodes (CLL only) leading to splenomegaly (CML and CLL), hepatomegaly or lymphadenopathy (CLL only)
- Lymphomas share bullet point #3 but blood counts are often normal.
List 3 major signs common to all leukaemias.
What are B-symptoms?
General leukaemia signs: conjunctival pallor, easy bruising, fever
B-symptoms are general symptoms of leukaemias and lymphomas:
Night sweats Intense pruritus Fever Weight loss Fatigue and weakness
List the investigational pathway of patients with suspected leukaemia / lymphoma.
■ Full blood count
■ Routine biochemistry including U&E, LFT, CRP and calcium
■ Coagulation profile (PT, APTT, fibrinogen)
■ Blood culture and screening for infection (if suspected)
■ Blood film
■ Peripheral blood immunophenotyping
■ Diagnostic bone marrow aspirate and trephine biopsy
– Morphology, immunophenotyping and genetic/molecular tests
■ If lymphoma suspected
– LDH
– Lymph node biopsy and histology
– CT imaging +/- PET-CT (for staging)
List 4 haematological and 5 non-haematological differentials to consider with leukaemias and lymphomas.
■ Haematological – Myelodysplastic syndrome – Aplastic anaemia – Megaloblastic anaemia due to B12/folate deficiency – Myelofibrosis
■ Non-haematological
– Metastatic solid tumours
– Infections (e.g. TB, hepatitis, infectious mononucleosis, malaria)
– Liver disease
– Connective tissue diseases (e.g. RA/Felty’s)
– Drugs and alcohol
List the main findings of AML on blood film.
Large, immature myeloid cells with butterfly-shaped bilobular nucleus and prominent nucleoli
Auer rods
Anaemia + thrombocytopaenia
What is APL?
Summarise the pathophysiology and treatment (presumably applicable to AML in general).
APL is acute promyelocytic leukaemia, a subtype of AML characterised by a marked increase in promyelocytes.
■ 10-15% of AMLs
■ 160 new cases/year in UK
■ M = F
■ Affects people of any age; median age of diagnosis = 50
Normal differentiation pathway:
myeloblast->promyelocyte->myelocyte->metamyelocyte->band cell->neutrophil
In APL there is failure of differentiation from promyelocyte to myelocyte due to translocation of PML (chromosome 15) and RARA (chromosome 17).PML-RARA causes differentiation block.
It is treated with all-trans retinoic acid (ATRA) and arsenic trioxide, which lead to degradation of PML-RARA. This cures APL in >80% of pts.
Summarise the treatment pathway for AML.
1 ■ Chemotherapy
– DA (daunorubucin, Ara-C/cytarabine) / CPX-351 (liposomal DA)
– FLAG-Ida (fludarabine, Ara-C/cytarabine, idarubicin)
2 ■ Monoclonal antibody
– Gemtuzumab ozogamicin (Mylotarg) (anti-CD33 mAb)
3 ■ Biological / targeted therapy
– Midostaurin, quizartinib, gilteritinib (FLT3 inhibitors)
– Ivosidenib, enasidenib (IDH inhibitors)
– Venetoclax (Bcl-2 inhibitor)
– Azacitidine (hypomethylating agent)
4 ■ Allogeneic stem cell transplantation
List the main findings of CML on blood film.
Immature neutrophils known as band cells (band shaped nucleus)
myeloid progenitors (big dark blobs)
some later differentiated eosinophil precursors
BUT some mature neutrophils may be present
Anaemia + thrombocytopaenia
Summarise CML epidemiology, presentation pathophysiology and treatment.
■ 15% of leukaemias
■ 750 new cases/year in UK
■ M > F (slightly)
■ Affects people of any age; median age of diagnosis = 60-65
■ Very rare in children; uncommon in young adults
Clinical presentation:
■ Vague symptoms (fatigue, weight loss, infection, bleeding), or asymptomatic
■ If inadequately treated can transform to AML (blast crisis)
- Caused by Philadelphia chromosome, caused by translocation of ABL (chromosome 9) and BCR (chromosome 22), causing uncontrolled proliferation through constitutive tyrosine kinase activity.
- Treatment is through imatinib, which prevents constitutive tyrosine kinase activity, or other newer generation tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib or ponatinib.
- Imatinib resistance can occur through (1) BCR-ABL mutation, (2) amplification and overexpression (3) drug efflux and (4) activation of alternate pathways. This can lead to relapse.
List the main findings of CLL on blood film.
Many lymphoid cells (small, round cells with the nucleus occupying most of the cell)
Smear cells, which are lymphocytes whose cell membranes break during preparation of the blood film
Anaemia + thrombocytopaenia
Summarise CLL epidemiology, presentation, diagnosis, pathophysiology and treatment.
■ Most common leukaemia type, 3800 new cases/year in UK
■ Elderly predisposition
■ M > F
■ Caucasians > Afro-Caribbeans > Asians
■ Asymptomatic lymphocytosis in some patients
■ Lymphadenopathy, hepatosplenomegaly, B-symptoms and/or features of bone
marrow failure in others
Diagnosis is special for CLL; made by immunophenotyping, in which a flow cytometer is used to identify cell surface markers including CD5, CD19 and CD20.
Pathophysiology:
- CLL cells overexpress BCL2, which lead to resistance to apoptosis.
- B cell receptors become dysfunctional, leading to overstimulation of proliferative pathways.
There is biological and clinical heterogeneity:
- 30% have stable disease, 45% have slowly progressing, 20% have progressive and <2% have spontaneous regression.
Treatment:
■ No cure
- Only indicated in symptomatic patients or those w/ anaemia, thrombocytopaenia or lymphocyte doubling time <6 months.
- Depends on cytogenetics
- Common chemoimmunotherapy drugs = purine analogues (e.g.) fludarabine, alkylating agents (e.g. chlorambucil), and monoclonal Abs (e.g. rituximab)
List the main findings of Hodgkin lymphoma on lymph node biopsy.
Hodgkin lymphoma lymph node biopsy findings:
Reed-Sternberg (owl’s eye) cells - crippled post-germinal B cells with bilobed nucleus and prominent eosinophilic inclusion-like nucleoli.
Many lymphocytes
Summarise Hodgkin lymphoma epidemiology, diagnosis, presentation, diagnosis, pathophysiology and treatment.
Epidemiology: ■ 2100 new cases/year in UK ■ M > F (slightly) ■ Affects people of any age ■ Most commonly affect those age 20-40 and >75
Route of diagnosis: blood counts normal but CT shows lymphadenopathy and sometimes mediastinal mass -> perform biopsy of lymph node.
Clinical presentation:
■ B-symptoms, pruritus, lymphadenopathy, mediastinal lymph node mass
■ 5-year survival >80%
Pathophysiology:
- Dependent on microenvironment.
- EBV1 infection and certain gene amplification leads to upregulation of upregulation of PDL1 extracellular ligands.
- PDL1 ligands bind to PD1 receptors on T cells to suppress cytotoxic responses against the lymphoma cell.
Treatment:
1 ■ Chemotherapy + radiotherapy first line treatment
– ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
– BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
procarbazine, prednisolone)
– ChlVVP (chlorambucin, vinblastine, procarbazine, prednisolone)
2 ■ Immunotherapy:
- Monoclonal antibodies against CD30 receptors on lymphoma cells, e.g. brentuximab vedotin
- Immune checkpoint (PD-1) inhibitor - blocks immune suppression against lymphoma cells through PD1 receptors - good for patients who relapse on chemotherapy, e.g. nivolumab an pembrolizumab
3 ■ Autologous stem cell transplantation (occasionally allogeneic)
List the main findings of non-Hodgkin lymphoma on lymph node biopsy.
Many lymphoid cells undergoing mitosis
Differentiating factor from Hodgkin lymphoma is the absence of Reed-Sternberg (butterfly) cells.
Immunohistochemistry positive for CD20 and BCL6, but negative for CD3
What is diffuse large B-cell lymphoma?
Summarise non-Hodgkin lymphoma epidemiology, diagnosis, presentation, diagnosis, pathophysiology and treatment.
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma
Route of diagnosis similar to Hodgkin lymphoma: blood counts normal but CT shows lymphadenopathy and sometimes mediastinal mass -> perform biopsy of lymph node.
Epidemiology: ■ 5500 new cases/year in UK ■ M > F (slightly) ■ Affects people of any age ■ Incidence increases with age; more common in those >65 - ~Twice as common as Hodgkin lymphoma.
Clinical presentation:
■ B-symptoms, bulky lymphadenopathy, hepatosplenomegaly, other symptoms
depending on location of the lymphoma
■ 5-year survival 50-65%
Pathophysiology:
Treatment:
■ Chemotherapy + anti-CD20 monoclonal antibody
– R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,
prednisolone)
– R-CODOX-M/R-IVAC (rituximab, cyclophosphamide, doxorubicin,
vincristine, methotrexate, etoposide, ifosfamide, cytarabine/Ara-C)
– R-ESHAP (rituximab, cisplatin, etoposide, cytarabine/Ara-C prednisolone)
– R-ICE (rituximab, ifosfamide, carboplatin, etoposide)
– R-GDP (rituximab, gemcitabine, dexamethasone, cisplatin)
■ CAR T-cell therapy: remove T cells from the blood, return rest of blood to pt, engineer T cells using a virus to make chimeric antigen receptors (CARs), return T cells to pt blood which attack the lymphoma. NB can cause cytokine release syndrome (neurotoxicity, haemodynamic instability, organ dysfunction).
– Tisagenlecleucel (Kymriah) (CD19 CAR T-cell)
■ Autologous stem cell transplantation (occasionally allogeneic)
