Lymphocytosis Flashcards

1
Q

reactive lymphocytosis

A

a polyclonal proliferation of T-Cells, almost always due to infection. excess of 4.0<10^9 for absolute lymphocyte count

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2
Q

lymphocyte populations in the blood

A

T cells: 60-80%, 70% of them being helper T cells and 30% of the T cell population being CD8+ cells B cells: 10-20% NK cells: 5-10%

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3
Q

neoplastic. lymphocytosis

A

monoclonal proliferation of B cells 1. chronic lymphocytic leukemia 2. acute lymphoblastic leukemia

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4
Q

reactive lymphocytosis history and physical examination

A

Reactive Lymphocytosis History: Consistent with viral infection  fever, chills, night sweats  cough (non-productive), sore throat  headache, muscle aches  general malaise-loss of appetite  photophobia  rash Physical Examination: the patient may have:  pharyngitis  meningismus  rash  jaundice  Lymphadenopathy (tender)  hepatomegaly/splenomegaly  shortness of breath

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5
Q

Ddx for findings of reactive lymphocytosis

A

Differential diagnosis:  INFECTIONS:  Epstein-Barr virus (mononucleosis)  cytomegalovirus (CMV)  rubella  mumps  pertussis  infectious hepatitis  HIV seroconversion

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6
Q

Symptoms of EBV (cause of reactive lymphocytosis)

A

Fever  Tender lymph nodes  Fatigue – often extended duration  May have palpable splenomegaly  May have hepatitis  Typical age – teens/20s  Not necessarily aware of “sick contacts”

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7
Q

investigation/protocols when someone presents with suspected reactive lymphocytosis

A

Investigations: A neoplastic cause must be excluded. Differentiating factors include:  History - eg time frame - symptoms not improving (fever, fatigue; pallor)  Physical exam: large organomegaly (if splenomeagly, maybe EBV)? or lymphadenopathy, petechiae  Lab - blood smear - atypical lymphocytes vs. blast cells  flow cytometry: polyclonal increase in T-cells  NB: complete blood count and differential -bone marrow examination not usually needed

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8
Q

appearance of atypical lymphocytes

A

larger than normal lymphocytes, nucleus is more irregular

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9
Q

natural history/prognosis/ complications of reactive lymphocytosis

A

no complications due to lymphocytosis. prognosis generally excellent with supportive care. repeat blood work when they are feeling better in a few weeks

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10
Q

3 specific infectious illnesses to be wary of when someone presents with reactive lymphocytosis

A
  1. pertussis– gram negative bacteria 2. rubella– measels 3. cytomegalovirus (CMV)
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11
Q

Summary to reactive lymphocytosis

Summary: 1. Reactive lymphocytosis is usually due to infection 2. History/physical exam most important to distinguish
from neoplastic cause 3. Laboratory investigations show a polyclonal
lymphocytosis 4. Prognosis generally very good with supportive
measures 5. Most simple solution is to repeat blood work when they
are feeling better in a few weeks

A
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12
Q

outline the appraoch to the classification of hematological malignancies (name the myeloid and lymphoid diseases)

A
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13
Q

outline approach to diagnosis/classification of lymphomas (hodgkin vs non-hodgkin)

A
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14
Q

most common adult leukemia

A

CLL. incidence increaes with age

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15
Q

what is CLL

A

A neoplastic disease characterized by the
clonal proliferation and accumulation of small,
mature –appearing immunologically
incompetent
B lymphocytes in the blood,
marrow, lymph nodes and spleen

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16
Q

what type of appearance of the lymphocytes in classic CLL?

A

soccer ball lymphocytes. condensed areas of nuclear material

17
Q

what finding on the PBS would you see with CLL

A

smudge cells and soccer ball lymphocytes

18
Q

how does ethnicity play a rolein CLL

A

seen more in caucasians. also seen more in males.

19
Q

name the B cell malignancies based on state of b cell maturation

A

the more mature of the B cell, the less proliferative. the least mature cancer cells are the most aggressive.

20
Q

which test is required for the diagnosis of CLL?

A

cytogenetic analysis of peripheral blood or bone marrow.

-immunophenotyping and flow cytometru

21
Q

outline the APPROACH to the diagnosis of CLL

A

Diagnosis
– History

– Physical exam

– Bloodwork
• CBC, flow cytometry, immunoglobulins, chemistry – Lymph node biopsy

  • If lymphoma is high on differential diagnosis – Bone marrow aspiration and biopsy
  • Not usually required
22
Q

typical phenotypes of B cells in CLL

A

CD5+, CD19+, CD23+, DimCD20, Dim Surface Lg

Minimum needed to confirm diagnosis is
≥ 5 x 109/L B lymphocytes in peripheral blood for ≥ 3
months1 (if less, called “monoclonal B cell lymphocytosis”)

24
Q

general and clinical features of CLL

A
  • 25% are asymptomatic when caught. some may have some weight loss.
  • minimal lymphaenopathy or unexplained lymphocytosis.
  • possible systemic symptoms of weight loss, recurrent infections (particularly encapsulated organisms Streptococcus pnemoniae, Klebsiella pneumonia, group B streptococci, Escherichia coli, Neisseria meningitides and Haemophilus influenzae), bleeding or fatigue/shortness of breath
  • clinical features:
  • lymphadenopathy (non tender, asymptomatic)
  • organomegaly (splenomegaly due to leukemic cell infiltrate, can cause cytopenia)
  • cytopenias including anemia and thrombocytopenia due to splenic sequestration, autoimmune, or marrow infiltration.
25
explain the rai and binet staging of CLL
26
indiciations for CLL treatment.
most of them are "watch and wait" cases, there is no evidence that early treatmnet prolongs survival in these patients. when to treat: Lymphocyte doubling time of less than 6 months • Systemic symptoms • Symptomatic lymphadenopathy or splenomegaly • Significant anemia (Hgb \<110) or thrombocytopenia (platelets \<100) – From bone marrow involvement – Autoimmune You don't need to treat in the early stages with the exception being patients with a rapid diseas eprogression (lymphocyte doubling time less than 6 months)
27
28
which antibodies do rituximab and alemtuzumab cover?
29
why are B cell receptors important to CLL cells?
• The B-cell receptor is an immunoglobulin (Ig) receptor on CLL cells – activated BCR is essential for CLL cell survival • BCR signalling is enhanced in cells with unmutated IgV H • Microbial or autoantigens bind BCR, causing phosphorylation • Phosphorylation **induces survival** signals via downstream kinases - we need to inhibit the B cell receptor
30
benefits and risk to B cell rece3ptor inhibitors
* Oral agents • No significant myelosuppression * Continued until progression (? compliance) • Unusual side effects (colitis from idelalisib, atrial fibrillation from ibrutinib) • Interestingly, no benefit to addition of rituximab to ibrutinib in CLL (so value of anti-CD20 mAbs with novel agents unclear)
31
\_\_\_\_ receptor is overexpressed in CLL and other cancers. what does this do?
32
how are drugs starting to restore apoptosis in cll cells?
through BCL2 inhibition (venetoclax)
33
study this diagram:
34
Note: Many patients are treated with watchful-waiting – When treatment is required, it is used to control symptoms (lymphadenopathy/cytopenias) – The only known curative treatment is stem cell transplant (and possibly highly intensive chemo in very young patients) (ie most patients will experience relapse(s) and re-treatment