M. Acute Leukemia (L15) Flashcards
What percentage of bone marrow cells are blasts normally? What percentage is seen in Acute Leukemia?
- < 3%
* >20%
What is the general pathophysiology of Acute Leukemia?
- Disruption of hematopoiesis –> inability for cells to mature –> buildup of myloid or lymphoid blasts/stem cells
- Proliferative cells crowd out normal cells in bone marrow –> acute presentation of anemia, thrombocytopenia & neutropenia
- Blasts enter blood –> increased (lymphocytic or myelocytic) WBC in peripheral blood (large immature cells with little cytoplasm and nucleolus)
What “step” in hematopoiesis are acute leukemias “stuck” in?
• Transition from HSC to lymphoblast and myloblast but then get stuck
What are the 2 main types of Acute Leukemia & what type of proliferative cell type is present? Which is most common? Mnemonic?
• Acute Myloid Leukemia (AML) = myloblasts
• Acute Lymphoid Leukemia (ALL) = Lymphoblasts
• AML is most common
M for More (L for little)
How does Acute Leukemia present on Bone Marrow Biopsy?
• 100% cellularity (no fat cells)
What is the “rule of thumb” to estimate what percentage of bone marrow should normally be cellular?
100 – age
What age groups are AML & ALL found in? Mnemonic?
- ALL = children (Think L for little)
* AML = adults (M = more for more common)
Time wise, what is the onset of Acute Leukemia?
- Presents with severe symptoms within a few weeks
* Can rapidly become fatal if not treated
What is the clinical presentation for Acute Leukemia?
- Crowding in BM by proliferative cells –> Pancytopenia –> below symptoms:
- Anemia –> fatigue & pallor
- Thrombocytopenia –> bleeds/bruising
- Decrease in functional WBCs –> infection & fever
- Leukocytosis as proliferative WBCs spill into circulation
- Hepatosplenomegaly
- Skin and gum WBC infiltration
- CNS involvement
What is the leading cause of non-traumatic death in children?
ALL
What ethnic group and sex is ALL most common in?
White boys
What increases the likelihood of ALL?
- Down syndrome
- Radiation
- Genetic syndromes
What are the 2 main types of ALL? Which is more common? Which is more aggressive?
- Pre-T Cell ALL
- Pre-B Cell ALL
- B is more common (85%)
- T is more aggressive
Where do Pre-T ALL masses present most often?
- Superior Mediastinum (where thymus is)
* Cause SOB as compress structures
What is the key finding for the L3 FAB classification on bone marow aspirate smear? What disease is it related with?
- Vacuoles
* Burkitts
What are characteristics that lead to a good prognosis for ALL? Bad?
- 50k bad)
- 1-10 yo (10 bad)
- Lack of CNS involvement (CNS involvement bad)
What is the overall prognosis of ALL?
- Good, 98% go into remission
* 2/3 have long term remission while 1/3 relapse
What age group is de novo AL seen in? What are the cytogenetic characteristics? Better or worse prognosis?
- Younger age children
- Less complex cytogenetics
- Better prognosis
What causes secondary Leukemia?
- Prior diagnosis of myeloproliferative disorder or myelodysplastic disorder
- Toxins (occupational, chemo, accidental)
What are Auer Rods diagnostic of?
AML
What is the overall prognosis of AML?
- 60% remission
* 80% of remission has reoccurrence
What is butterfly shaped nuclei diagnostic of?
• APL, a type of AML
How is the prognosis of ALL & AML changed if t(9:22) translocation is present?
Worse Prognosis
What mutation causes Acute Promyelocyte Leukemia (APL)?
• T(15:17) PML:RARalpha
• Fuses anti-apoptotic factor & retinoic acid receptor –> blocks myeloid proliferation
DIC PRONE
DIC is seen in what type of Acute Leukemia?
APL
What type of Acute Leukemia is one of the first examples of targeted gene therapy?
APL (AML)
What type of AL stains with myeloperoxidase (MPO)? Color of MPO?
AML
Dark blue
What is the main morphological feature of lymphoblasts and myloblasts?
• Large size which is mostly made up of nucleus
None specific esterase stains what cell type? Color of stain?
Megaloblasts
Greenish red color
What is a neoplastic buildup of lymphocytes called? How about mylocytes?
ALL
AML
How does incidence for AML & ALL change in relationship to age?
ALL = bimodal but much higher in kids than in elderly AML = risk increases with age
What does M3 in the FAB classification system signify?
APL
Does acute leukemia present with peripheral leukocytosis or leukopenia?
Either
There is a decrease in functional WBCs, but the proliferative WBCs may or may not spill into the circulation
Is extramedullary involvement more often seen in AML or ALL?
ALL
What condition can be a precursor to ALL?
Initially present as nodal or skin disorder –> progress to bone marrow
Most common cancer in newborn to 15yo? 15-40? 40-60? >60?
ALL
AML
AML (60%) or CML (40%)
CLL
4 types of AML based on lineage?
Acute Monocytic Leukemia
Acute Erythroid Leukemia
Acute Megacaryocytic Leukemia
Acute Promyelocytic Leukemia (APL)
What type of acute leukemia is associated with DIC?
APL (type of AML)
Patients with what type of AML are prone to bleeding?
APL because of the associated DIC
For what type of Acute Leukemia is all trans retinoic acid (Vit A) a treatment?
APL
What cytogenetic conditions are associated with a better ALL prognosis?
t(12:21)
Hyperploidy (Trisomy 4 & 10)
What cytogenetic conditions are associated with a worse ALL prognosis?
t(9:22)
t(1:19)
MLL gene
What is the L1 category of ALL?
Lymphoblasts with very little cytoplasm (very high N/c ratio)
What types of extramedullary involvement is seen in pre-T & pre-B ALL?
Both = CNS, Skin, Liver Spleen
B only = Gonads, Lymph nodes
Are neoplasms of precursors more common in children or adults? What about effector cell neoplasms?
Neoplasms of precursor cells tend to be more common in children, while those of antigen-dependent effector and memory cells tend to be more common in adults.
Where do different types of neoplastic cells go?
–neoplasms of bone marrow precursor cells are often acute leukemias;
–those of germinal center cells occur in follicular areas of lymph nodes and other tissues,
–those of memory B-cells are often found in sites of antigenic stimulation, such as the gastrointestinal tract.
What type of cells are building up in chronic leukemia?
Abnormal but relatively mature cells
How urgently must treatment be started for acute leukemias? Chronic?
Acute = begin immediately Chronic = sometimes observe for a while before begin
What is taken into account for FAB & WHO classifications?
FAB = morphology and cytochemistry WHO = morphology, cytochemistry & clinical presentation
What are Auer rods made of?
Fusion of primary granules
