Hematology Week 3: Mature Lymphoid Neoplasms Flashcards
Patient Presentation
Question 1
A Mature Lymphocytes
Most common mature lymphoid leukemia
Chronic Lymphocytic Leukemia (CLL)
CLL neoplasm of what kind of cells?
CLL is a neoplasm of mature monoclonal B-cells
What kind of cells?
Normal polyclonal B cells
What Kind of Cells?
Monoclonal B cells can choose only Kappa or Lambda, in this case this clonal expansion expressed only lambda
Clonal vs non-clonal
clonicity is a valuable diagnostic tool
Abnormal immunophenotype for CLL
CD5 and CD23 on B cells
CD5 is usually found on?
T cells
if found on B cells is indicative of CLL
or
CLL Peripheral blood smear characteristic features
5 listed
- scant cytoplasm
- dark nuclear chromatin
- small
- uniform size
- “Smudge cells”
CLL in the lymph node
referred to as small lymphocytic lymphoma
CLL and SLL
are the same entity
same genetics
same treatment
the difference is if they are found in the blood or tissue vs BM
CLL vs SLL
Epidemiology of CLL/SLL
- Most common leukemia of adults in the US
- Patients typically elderly
- often asymptomatic at diagnosis (incidental)
Most common leukemia in adults
CLL/SLL
CLL/SLL Characteristic Cell findings
monoclonal small B-cells with aberrant co-expression of CD5 and CD23
CLL/SLL Cytopenias from?
BM is filled up by CLL cells and is replaced by neoplastic cells
CLL/SLL immune disruption
2 listed
- Hypogammaglobulinemia -> infections
- Autoimmune phenomena -> anemia, thrombocytopenia
CLL/SLL clinical course
Typically indolent but variable
CLL follows the rule of 3rds
Staging in CLL
Rai System
&
Binet System
Lab studies for CLL/SLL
- CBC+Diff
- FISH (lesion at 17p is worst)
- CD49d expression (when not expressed is better prognosis)
- immunoglobulin heavy chain variable region somatic mutation (mutation is a good thing because that is what it is supposed to do)
When are CLL/SLL patients treated?
5 listed
- treat symptoms
- threatened end-organ function
- progressive bulky disease
- progressive anemia/thrombocytopenia
- not curable so treat for symptom relief if the benefit is worth the cost of toxic treatment
Symptoms treated for in CLL/SLL
4 listed
- Fever without infection
- Weight loss
- Night Sweats
- Severe fatigue
the most common reason for treating CLL/SLL
Progressive anemia/thrombocytopenia
How to treat CLL/SLL drug classes
4 listed
- Monoclonal Antibody
- Chemotherapy
- Biologic agents
- Combinations of them
Rituximab
- The prototype monoclonal antibody
- Anti-CD20
- Usually used in combo with chemo
Fludarabine
- Purine analog
- specific toxicities
- severe marrow toxicity
- autoimmune phenomena
- autoimmune hemolytic anemia
- ITP
Bendamustine and Chlorambucil
- Nitrogen mustards/alkylating agents
- Marrow suppressive
Ibrutinib
- Bruton tyrosine kinase inhibitor
- Oraol
- Extremely variable toxicity
- GI upset (diarrhea)
- bleeding
- a-fib
- immunosuppression
- joint pain
- nothing
Idelalisib
PI3 Kinase Inhibitor
Significant toxicity - infections (PJP pneumonia, CMV infection), liver toxicity
Hairy Cell Leukemia morphology
shaggy cytoplasm “hairy cells”
Hairy Cell Leukemia Immunophenotype
- Positive for TRAP (Tartrate-resistant acid phosphatase)
- Negative for CD5
BM of Hairy Cell Leukemia
difficult to get BM aspirate because cells are so tightly packed but can get a core biopsy
Treatment of Hairy Cell Leukemia
2 listed
Responds very well to purine analogs
- Cladribine
- Pentostatin
M Protein AKA
monoclonal paraprotein
M protein interpretation
aka m spike
can be IgM, IgG, IgA or whichever
Multiple Myeloma pathophysiology
4 listed
- neoplasm of clonal bone marrow plasma cells
- typically IgG or IgA
- Most cases have CRAB
- Hypercalcemia, Renal insufficiency, Anemia, Bone lytic lesions
- Produce large amounts of M-protein
Multiple Myeloma histological features
- very eccentric nucleus
- prominent “hof” perinuclear clearing (pale area by nucleus which is very prominent Golgi apparatus)
- bone marrow taken over by plasma cells
CRAB
- Hypercalcemia
- Renal insufficiency
- anemia
- bone lytic lesions
In Multpile Myeloma
Clues to Myeloma
5 listed
- Hypercalcemia - from bone resorption
- Renal Failure - Filtering light chains is toxic to the renal tubules
- Anemia - normal marrow is replaced by the plasma cells
- Pathologic bone fractures - bone remodeling leavs out bony lesions
- Rouleaux formation -Stacks of RBCs die to increased immunoglobulin
Monoclonal gammopathy of undetermined significance
clonal expansion of plasma cells but …
lower amount of M-protein
only few clonal plasma cells in bone marrow
NO CRAB
MGUS AKA
Monoclonal gammopathy of undetermined significance
MGUS Treatment
do not treat at this stage
MGUS evolution
this condition progresses to overt myeloma at the rate of 1-2% per year
Lymphoplasmacytic Lymphoma
Monoclonal plasma cells and monoclonal lymphocytes mixed together
What type of immunoglobulin in lymphoplasmacytic lymphoma?
IgM
Hyperviscosity of the blood along with IgM M protein
Waldenstrom Macroglobulinemia
M protein think about these diagnoses
3 listed
- Multiple Myeloma
- MGUS
- Lymphoplasmacytic lymphoma
LPL AKA
Lymphoplasmacytic lymphoma
A characteristic expression of LPL
- Hyperviscosity of the blood along with IgM M-protein
- Waldenstrom Macroglobulinemia
Treatment of Multiple Myeloma
Treatment of Multiple Myeloma is only indicated if?
- CRAB is present
- don’t need to have all of them but can have some of them
- not curable so only treat if it can benefit the patient
Treatment of Multiple Myeloma drug classes
4 listed
- Immunomodulators (i.e. Thalidomide)
- Proteasome inhibitors (Bortezomib)
- Corticosteroids
- Chemotherapy
Thalidomide Toxicities
Marrow suppression
peripheral neuropathy
highly regulated
teratogen (highly regulated)
Bortezomib Toxicities
Toxic Neuropathy
Chemotherapic agents in Multiple Myeloma
3 listed
- Cyclophosphamide
- Liposomal doxorubicin
- Melphalan
Autologous Stem Cell Transplant in Multiple Myeloma
can collect cells before over-exposure to marrow toxic drugs
Bone lesions in multiple myeloma
- Bisphosphanate therapy - same drugs used to treat osteoporosis
- bone lytic lesions can be on skull which is very dangerous
Clinical Overview
