Acute Myeloid Leukemia & Myelodysplastic Syndrome - Krafts Flashcards
What is the official definition of leukemia?
malignant proliferation of immature myeloid or lymphoid cells in the bone marrow
What are the two types of acute leukemia?
- Acute myeloid leukemia
- Acute lymphoblastic leukemia
What is the etiology behind leukemia?
- most are sporadic (spontaneous)
- toxins (benzene)
- genetic conditions increase chance
- e.g. Down’s syndrome
What is the cause of acute leukemia?
- clonal expansion
- maturation failure (arrest)
- get stuck somewhere in myelopoiesis
What is so bad about acute leukemia?
- Crowd out normal cells
- fill up marrow space
- no room for RBCs
- Inhibit normal cell function
- Infiltrate other organs (worst)
- especially bad if enter the brain
What are most morphologic cell types in acute leukemia?
Immature cells
(most blast cells)
What are the clinical findings in acute leukemia?
- sudden onset (days)
-
Symptoms of bone marrow failure
- fatigue (not enough red cells)
- infections (not enough white cells)
- bleeding (can’t make platelets)
- Bone pain (due to expanding marrow)
- Organ infiltration (liver, spleen, brain)
- leave bone marrow and enter organ
What are the laboratory findings in acute leukemia?
- Marked leukocytosis (really high white count)
- Blasts/immature cells in blood
- Anemia
- Thrombocytopenia
What is the “Old” Classification system of AML based on?
only morphology
What percent blast cells do you need to diagnose Acute Myeloid Leukemia?
Neet at least 20%
What charactizes a blast cell in Acute Myeloid Leukemia?
- Immature white cells:
- Large nucleus
- Small amount of cytoplasm
- Fine chromatin (see through it)
How do you know when a leukemia is myeloid?
- Dysgranulopoiesis
- nucleus is not segmenting properly (one big lobe)
- cytoplasm does not have any specific granulation (or unable to detect it at all)
- Auer rods
- long needle-like structures in cytoplasm
- only occur in malignant myeloid cells (usually only blast cells)
- not all cases have them
- Cytochemistry
- non-specific esterase stain - stains monocytes
- myeloperoxidase - stains neutrophils
- Immunophenotyping
- Cytogenetics
How is the “New” classification of AML different from the “old”?
- more characteristics than just morphology
- identifies cytogenetic abnormality
- has therapy-related category (developed after chemo)
- gives better idea of prognosis
What classifies AML as “M0”?
- least mature (so immature)
- barely differentiated into myeloid
- significantly increased myeloblast count
- bland cells
- no auer rods
- no granules
- can’t tell what they are
- MPO (myeloperoxidase) negative
- Need markers (on cell surface)
- flow cytometry detects these
What classifies AML as “M1”?
- <90% myeloblasts
- No maturation (all blasts, none beyond this stage)
- Auer rods present
- MPO (myeloperoxidase) positive
What classifies AML as “M2”?
- increased myeloblasts
- maturing neutrophils
- t(8;21) in some cases
- special translocation
- better prognosis
What classifies AML as “M3”?
- increased promyelocytes (at least 20%)
- not a lot of blast cells present
- Faggot cells (“bundle of sticks”)
- has a ton of auer rods
- DIC (disseminated intravascular coagulation)
- cells bust open and lead to clots
- granules stimulate coagulation
- use up all coag factors and then start bleeding
-
t(15;17) in ALL cases
- particular translocation that gives the patient a better prognosis (best for AML)
- involves retinoic acid receptor - drug is Tretinoin (ATRA)
- allows immature cells to mature
What classifies AML as “M4”?
- Increased myeloblasts (at least 20% present)
- Increased monocytic cells
- Extramedullary tumor masses
- tumor leaves bone marrow and goes into tissues (esp. CNS, gums)
- inv(16) in some cases
- well-known translocation that gives patient a better prognosis
What classifies AML as “M5”?
- Increased monocytic cells
- promonocyte (overlapping, folds in nucleus)
- NSE (non-specific esterase) positive
- M5A (monoblasts) and M5B (promonocytes)
- Extramedullary tumor masses
What classifies AML as “M6”?
- increased erythroblasts
- increased myeloblasts
- dyserythropoiesis
- red cells are not growing properly
- look abnormal
What classifies AML as “M7”?
- Increased megakaryoblasts
- Bland blasts
- MPO (myeloperoxidase) negative
- Need markers
- identified by flow cytometry
What are the four specific types of AML with genetic abnormalities?
- t(8;21)
- AML-M2
- inv(16)
- AML-4
- neutrophilic and monocytic
- super dark granules
- *t(15;17)
- in ALL cases of AML-3
- treat with ATRA to let cells mature
- 11q23
- not associated with any one leukemia
- monocytic AML
- bad prognosis
What is the significant about AML with FLT-3 mutation?
- Mutation of FLT-3 (a tyrosine kinase)
- allows white cell count to get REALLY high
- increased proliferation rate of WBCs
- Present in 1/3 of cases of AML!
- Monocytic cells
- Poor prognosis
What is significant about AML with multilineage dysplasia?
- Not very common
- Type of acute myeloid leukemia that has dysplasia (funny looking cells) in more than one myeloid lineage
- at least 20% blasts + dysplasia in at least 2 cell lines
- More common in Elderly
-
Severe pancytopenia
- all cell counts are DOWN
- Chromosome abnormalities (5, 7)
- Poor prognosis
What is significant about therapy-related AML?
- Previous chemotherapy treatment
- alkylating agents (Busulfan) or topoisomerase II inhibitors (Etoposide)
- 2-5 years to onset
- Chromosomal abnormalities sometimes (5, 7, 11q23)
- VERY HARD TO TREAT!!!!
How do you treat AML?
- Know type of AML
- specific treatments for some (ATRA)
- Chemotherapy
- get rid of bulk of tumor
- Bone marrow transplant
- if patient can tolerate it
- do not need for AML-M3
- only hope for permanent cure
What is the prognosis of AML?
- Dismal, bad
- better prognosis in kids
- t(8;21), inv(16), t(15;17) have better prognosis
- FLT-3, therapy-related have worse prognosis
What classifies Myelodysplastic Syndrome (MDS)?
- Problem: abnormal stem cells
- Dysmyelopoiesis
- May have increased blasts
- May evolve into acute leukemia
- Varied types & features
What does dysplasia look like in red cells?
Megaloblastic nuclei
Fragmentation
What does dysplasia look like in neutrophils?
hypogranulation
hyposegmentation
What does dysplasia look like in megakaryocytes?
small, non-lobulated cells
(actually get smaller)
What are the clinical/lab findings in Myelodysplastic Syndrome?
- Older patients
- Asymptomatic OR bone marrow failure symptoms
- fatigue
- infection
- bleeding
- Macrocytic anemia
What is the treatment for Myelodysplastic Syndrome?
- Low-grade
- support
- follow
- High-grade
- be aggressive
- could turn into leukemia
