Week 10. Neoplastic Lymphoproliferative Disorders Flashcards Preview

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Flashcards in Week 10. Neoplastic Lymphoproliferative Disorders Deck (21):

What are leukaemias?

Accumulation of malignant white blood cells in the bone marrow and blood.


What are the classifications of leukaemias?



Acute=fast onset. Chronic=onset over long time


What is the lymphatic system and what are lymphomas?

Lymphatic system is part of body's immune system.
Network of branching thin tubes, branch into tissues throughout the body.
Lymphatic vessels carry lymph, a colourless watery fluid, that contains lymphocytes.
Lymphomas are cancers which develop in lymphatic system


What is lymphoid leukaemia?

Lymphoid leukaemia is cancer of lymphoid cells in the bone marrow.
Lymphoid cells are those which normally become lymphocytes. ]Mature lymphocytes are mainly antibody producing cells but some have other roles in the immune system.
can be acute or chronic.


What can the lymphoid stem cell become?

Can have T or B cell malignancy. Good to determine which one to get treatment right.


Types of lymphoproliferative leukaemias?

1. Acute lymphoblastic leukaemia (ALL)- usually blasts, immature cells.
2. Chronic lymphocytic leukaemia (CLL) - mature cells usually effected.


What is ALL?

Acute lymphoblastic leukaemia- Clonal disorder of lymphoid cells. Malignant transformation can occur in haemopoietic stem cells or early progenitor cells. Usually in children under 15.


Incidence of acute lymphoblastic leukaemia in children?

3-4 cases per 100,000
Not as many children who go to nurseries get it. Might be due to 2nd transforming event at age 3/4.

MOst common malignancy in children. peak 2-5 years. Good cure rate because so much research 70-90%

Childhood disease different from adult disease- different biology.


Incidences of ALL in adults?

~1 case per 100,000
ALL increases in adults after age 75
More random, no identifiable causes/mutations have been found.
Treatable in some cases with aggressive treatment and stem cell transplantation.


In ALL what does genetic damage cause?

Can cause:
An increase in cell proliferation
reduction in cell death (apoptosis)
inhibition of cell differentiation

Blasts accumulate because the cells don't mature properly or differentiate, they aren't fully functional. Get accumulation of progenitor cells- blast cells.


clinical features of ALL?

Bone marrow failure and organ infiltration.

There are lots of immature cells failing to die so bone marrow is very full and failing to produce other cells. end up with anaemia, thrombocytopenia and other infections because other WBCs aren't produced enough.
Decreased RBC and platelet count. Splenomegaly may be seen.
Bone marrow overcrowded- tender bones.
Hepatomegaly- like splenomegaly but in liver.
Vague symptoms- tired, pale.


classes of ALL?

FAB classification based on morphology and immunophenotyping L1-L3

L1- blast cells small, uniform high nuclear to cytoplasmic ratio.
L2- blast cells larger, hetergeneous, lower nuclear to cytoplasmic ratio.
L3- cytoplasmic vacuoles-> holes in the cells themselves


What would ALL diagnosis be based on? (lab findings)

Full blood coutn: anaemia, thrombocytopenia.
Leukocytosis: 20% blasts in blood. normally 2%
Morphology- hyper-cellular bone marrow containing blasts.
Immunophenotyping: antigens on cell surface that correlate with lineage and maturity
Cytogenetics: specific chromosomal changes in ALL
DNA analysis shows clonality of immunoglobin or T cell receptor rearrangmeents in ALL
(list in order of steps)


WHat are the prognoses for 2 molecular mutations? In ALL

Translocation betwen 12 and 21 is a common mutation aand good prognosis-> 90% curable.
Philadelphia chromosome. t(9;22). bad prognosis. Only seen in 3% of children who have ALL. 30% adults.


ALL- describe philadelphia chromosome

Recripical translocation between long arm of chromosomes 9 and 22.
Results in fusion of protooncogene ABL with the BCR gene on 22.
Makes chimeric BCR-ABL gene encoding for a 210 kDa protein- causes production of tyrosine kinase, stimulates production of abnormal blood cells.
Leads to increased cell cycling and resistance to apoptosis.


3 treatement options for ALL?

1. Cytotoxic drugs have defined phases.
1st phase: remission-reduction. High dose, reduces or eradicated malignant cells from the bone marrow. Will act on healthy cells too. Non-specific.
2nd phase: post-induction chemotherapy

2. Stem cell transplantation. last resort.

3. Supportive therapy: blood transfusions, antibiotics to treat infections, treat effects of chemotherapy.


describe incidenced of CLL

Most common leukaemia in western world (rare in asia)
Peak incidence 60-80 yrs old.
Disorder primarily of B lymphocytes which fail to apoptose.
Accumulate in blood, bone marrow, lymph nodes and spleen.
2:1 male to female ratio.

Cause of disease unknown. no particular mutations. but common chromosomal abnormalities e.g. deletions in 11q and 13q.


Clinical features of CLL?

Many cases of CLL symptomless, just diagnosed on routine blood tests.
Presenting deatures= lymphadenopathy and potentially bone marrow failure.
Lymphocytosis observed with majority of cells beign smear (smudge) cells.

smudge cells= leukocytes that have been damaged during prep of smear, due to cell fragility.


Treatment options for CLL?

Oral chlorambucil (alkylating agent): lower the lymphocyt count.
Monoclonal antibodies such as rituximab (anti-cd20)
Compath 1H (anti-cd52) used in patients that dont respond to initial treatment.
These get your immune system to destroy the cells. want to reduce number of malignant WBCs.


Extra reading- about 1st phase chemotherapy

1st phase of chemotherapy is remission induction- quickly and aggresively kill most the tumour cells in the patient.
In Philadelphia chromosome-positive ALL, the intensity of initial induction treatment may be less than has been traditionally given.

Yanada M (2015). "Time to tune the treatment of Ph+ ALL". Blood 125 (24): 3674–5. doi:10.1182/blood-2015-04-641704. PMID 26069331.


Extra reading about how caucasians are more likely than africans to get ALL

Genome-wide association studies have found associations with a number of genetic single-nucleotide polymorphisms, including ARID5B, IKZF1 and CEBPE.[21]:1388[43][45][46][47]

There is an increased incidence in people with Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, X-linked agammaglobulinemia, and severe combined immunodeficiency. There is an increased risk in people with a family history of autoimmune diseases, particularly autoimmune thyroid diseases (namely Graves' disease or Hashimoto's thyroiditis).