What does this patient have?
Fatigue, pharyngitis, splenohepatomegaly
What does this patient have?
What is absolute lymphocytosis?
What is the difference between reactive or neoplastic? (Duration, Morphology, Absolute Count, Associated Clinical Findings, Flow cytometery)
>4,000/microL of lymphocytes
Reactive - Acute Duration, Heterogenous, 10-12K or less, Flow reveals polyclonal
Neoplastic - Chronic Duration, Homogenous (Monotonous), 20-40K, Flow reveals monoclonal
Clinical findings are actually pretty common, specific things such as excessive fatigue and weight loss push towards neoplastic
What other viruses/pathogens cause mono-like syndromes?
CMV, Adeno, Acute HIV, Toxo
How do we assess B cells for clonality?
Light chain restriction on cell surface (kappa v lambda) via flow or immunohistochem
IgH variable gene PCR - One (mono) vs multiple (poly) rearrangements
Immunophenotypic aberrancy (e.g. CD5 (T-cell marker) expression on B cells)
T/NK assessment for clonality?
TCR gene PCR
Flow assessment for clonality? What's left vs right?
Left - Polyclonal
Right - Monoclonal
What is this cell indicative of disease?
What kind of cell is this?
What would be the next step to characterize these cells?
Immature cell (Lymphoblast)
Flow cytometery (determine clonality and lineage)
What is a smudge cell count used for?
Is it specific?
No, also occurs with mono, but it is classically tested
What markers are indivative for B-ALL?
CD10+/CD19+ (B-cell specific)/CD34+ (Blast specific))
CD3- (T-cell)/CD20- (Mature B-cell)
Where can B-ALL expand to?
Is hypocellularity a finding with ALL?
Not in bone marrow (hypercellulairty in bone marrow)
Cytopenias would appear in peripheral blood
What are good prognostic genetics for B-ALL?
What are bad prognostic genetics?
Where are the karyotypes taken from?
Good: Hyperdiploidy, t(12;21)
Bad: Hypodiploidy, t(9;22),11q23 abnormalities (MLL)
They are taken from the specific aberrant cells, can be compared to a buccal swab which should find normal karyotypes
What is a large mediastinal mass from an adolescent male indicates?
What would be a charactersitic immunophenotypic finding of this tumor?
Ratio of B-ALL vs T-ALL
85% to 15%
Definition of acute leukemia
Can it involve extramedullary sites?
What are the two big categories and the morphology/immunophenotype?
>20% blasts in the blood or bone marrow
Myeloid - CD13,14,15,33,117 w/w/o Auer rods
Lymphoid - CD3,CD19,CD20
What is the pre-leukemic state of AML?
What are the classification states of AML?
Myelodysplasia - Pre-leukemia
AML w/recurrent cytogenic abnormalities
AML w/myelodysplasia-associated changes
Prognostic factors in B-ALL
Age (2-10 is good, otherwise bad)
Elevated WBC count is poor (>100K/uL)
CSF involvement is poor
Marrow involvement at day 15 is poor
Treatment of ALL (stages)
Induction - Initiate remission
Intensification - Keep up remission
CNS Prophylaxis - Chemo doesn't enter the brain
How is CNS prophylaxis done for ALL?
What other part of the body needs special concern for ALL?
Irradiation or IT methotrexate
Testes also is protected from chemo
Cure rate for Adult vs Pediatric ALL
Causes of differences?
Adult - 50%
Pediatric - 80-90%
Differences in disease and resillience of the body to handle the chemo
What is so special about bispecific T-cell engaging (BiTE) antibody?
Directs cytotoxic T-cells to CD19 expressing B-cells to kill them
How is prognosis for Philidelphia ALL?
What drug improves it?
Horribly bad (7%)
Dasatinib raises it up to 40%+
What is the characteristic cell description for CLL?
What are the immunophenotype of CLL?
"Soccer ball" or "Ginger-snap"
CD5+/CD19+/CD20+/CD23+ with monoclonality (single light chain)
What are the causes of anemia in CLL?
Primarily due to crowding out in bone marrow
Secondarily due to immune-mediated destruction of precursors
Prognostic Indicators in CLL/SLL
Good: Low Rai stage, Mutated Ig Heavy Variable (IGHV) gene, Deletion 13q
Bad: High Rai stage, Unmutated IGHV gene, CD38/ZAP70 expression, Deletion 11q,17p
What is the classification criteria for small B cell leukemia/lymphomas with
"Natural" prognosis based on stage for CLL/SLL
Stage 0 - 150 months
Stage I - 101 months
Stage II - 71 months
Stages III/IV - 9 Months
What are CLL/SLL indications to treat?
What do we treat with?
Lab: Rapid lymphocyte doubling time (< 6 months), Hgb < 10g/dL (Stage III), Platelets < 100k/uL
Clinical: Autoimmune anemia or thrombocytopenia, richter transformation (large cell transformation), enlaarging symptomatic lymph nodes, B symptoms
What are we trying to do with 17p CLL patients?
Target B-cell signaling (specifically Rituximab (PI3 Kinase) with a BTK inhibitor)
What diseases have atypical lymphocytes +/- lymphocytosis?
Leukemic lymphoma (follicular, mantle, etc)
Hairy cell leukemia
Adult T cell leukemia/lymphoma
Classic presentation of Hairy cell leukemia:
Demographics, symptoms, exam finding, immunophenotyping
40-60 y/o males
Any symptom associated with pancytopenia
Flow diagnosis: Bright CD11c and CD22 expression; TRAP+
What cells are affected by Sezary syndrome?
Whats the triad?
What is the classical histology?
Which skin condition is it affiliated with?
Potential prognostic complication?
CD4+ T-cell neoplasm
Triad of erythroderma, generalized, lymphadenopathy, circulating sezary cells
Cells have "cerebriform nuclei"
Related to mycosis fungoides
SS/MF may transform to aggressive T-cell tumor
What is adult T-cell leukemia/lymphoma associated with cell wise?
What virus is it paired with?
Place in world associated with?
HTLV-1 Associated (Not specific)
Japan, Caribbean, Africa
Flower cell with lymphocytosis
What cells are associated with large granular lymphoytic leukemia?
What is the clinical course?
What does it present with?
What other diseases is it associated with?
Cytotoxic T cells, NK cells
Neutropenia, anemia, splenomegaly
Autoimmune disorders (rheumatoid arthritis)