6b- Lymphocytosis/lymphoid leukemia Flashcards
What is CLL/SLL?
- CLL/SLL= chronic lymphocytic leukemia/small lymphocytic lymphoma
- Most common leukemia in the western world
What are the demographics and presentation of CLL/SLL?
- Mean age at diagnosis= 65 yo
- Symptoms:
- most patients asymptomatic (indolent disease)
- worked up due to lymphocytosis
- may have lymphadenopathy
What is Richter syndrome?
The transformation of an indolent CLL/SLL to aggressive B cell lymphoma (happens in 2-8% of cases)
What are some histological findings for CLL/SLL leukemia?
- Leukemia= blood and BM involvement (“wet”)
- Knotting lymphocyte chromatin
- Smudge cells (not diagnostic for CLL/SLL but commonly seen)
- BM lesions
What are some histological findings for CLL/SLL lymphoma?
- Tissue based (lymph nodes, spleen, MALT)
- Proliferation centers (don’t worry about identifying on exam)
- pale, ill-defined nodules
- prolymphocytes admixed with small lymphocytes with pale cytoplasm (“Soccer ball cells”)
How do you differentiate types of Small B cell leukemia/lymphoma?
- CD5
- CD23
- CD10
Describe some good (3) and bad (4) prognostic factors for CLL/SLL
- Good
- low Rai stage
- mutated Ig Heavy Variable (IGHV) gene
- deletion 13q
- Bad
- high Rai stage
- unmutated IGHV gene
- CD38/ZAP-70 expression
- deletion 11q, 17p
Describe Rai staging system
For staging CLL/SLL
(better prognosis the lower the stage)
What are the indications to treat CLL/SLL?
- treat Rai stages III/IV
- labs
- rapid lymphocyte doubling time (<6 months)
- Hgb < 10g/dL
- Platelets < 100k/uL
- clinical
- autoimmune anemia/thrombocytopenia
- richter transformation
- enlarging symptomatic (or bothersome) lymph nodes
What are the treatment options for CLL/SLL?
- chemotherapy
- targeted cell therapy
- BCL2 inh
- PI3 kinase
- BTK inh
- immunotherapy
- CD20 antibodies
- cellular therapy
- stem cell (BM) transplant
- CAR-T cells
What is FCR treatment?
- For CLL/SLL
- Fludarabine + Rituximab + Cyclophosphamide
- Combination of drugs for complicated course of treatment
- Works better/worse depending on cytogenetics:
- Better for trisomy 12, 13q and 11q deletion
- Worse for 17p deletion
What is ibrutinib?
- Oral irreversible BTK inhibitor
- inhibits proliferation and survival
- inhibits adhesion
- modulates chemotaxes and trafficking
- Effectiveness NOT determined by cytogenetics
- NOT a cure (need to be on a daily pill for life)
What is venetoclax?
- BCL2 inhibitor
- pushes cells to commit suicide (normally BCL2 inhibits apoptotic pathway)
- Better outcomes than chemotherapy
What disorders can present with atypical lymphocytes with OR without lymphocytosis?
- CLL/SLL (usually presents with lymphocytosis)
- Leukemic lymphoma (follicular, mantle, etc)
- Hairy cell leukemia
- Adult T cell leukemia/lymphoma
- Sezary syndrome
What disease does this blood smear likely represent?
Hairy cell leukemia
Describe hairy cell leukemia
- 40-60 yo males
- splenomegaly (red pulp infiltration)
- pancytopenia
- “hairy” lymphocytes +/- lymphocytosis
- TRAP + cells
- BM fibrosis leading to “dry” spinal tap
- Flow cytometry -> bright CD11c and CD22 expression
- indolent disease
What disease does this blood smear likely represent?
Sezary syndrome (lymphocytes with “cerebriform” nuclei)
Describe Sezary syndrome
- CD4 T cell neoplasm
- triad: erythroderma, generalized lymphadenopathy, circulating sezary cells (cerebriform nuclei)
- related to mycosis fungoides
- may transform into aggressive T cell tumor
What is mycosis fungoides?
Sezary cell infiltration of the epidermis
What disease does this blood smear likely represent?
Adult T cell leukemia/lymphoma (“flower” cells)
Describe adult T cell leukemia/lymphoma
- CD4 T cell neoplasm
- associated with retroviral infection (HTLV-1)
- more common in Japan, Caribbean, and Africa
- “flower cell” with lymphocytosis
- hypercalcemia
- aggressive clinical course
What disease does this blood smear likely represent?
Large granular lymphocytic leukemia
Describe large granular lymphocytic leukemia
- lymphoporliferative disorder of CD8 T cells
- indolent
- usually presents with neutropenia, anemia, and splenomegaly
- associated with autoimmune disease (esp rheumatoid arthritis)
