Acute Myeloid Leukemia and Myelodysplastic Syndromes Dr. Krafts 5/9/14 Flashcards
Acute v. Chronic Leukemia
Acute Leukemia
- Sudden onset (over period of day (s))
- Can occur in either adults or children
- Rapidly fatal without treatment (prognosis poor even w/ Tx)
- Composed of immature cells (blasts) (located on top part of chart)
Chronic
- Slow onset (months)
- Occurs only in adults***
- Longer course
- Composed of mature cells (bottom of chart)
Leukemia from neutrophil series
CML
Leukemia w/ a large number of normal looking mature lymphocytes
CLL
Definition, cause, and badness of acute leukemia
Definition: malignant proliferation of immature myeloid or lymphoid cells in the bone marrow
Cause (many times we don’t know the cause)
- Clonal expansion
- Maturation failure (cells expanding and dividing more than normal also)(Tx removes block in maturation)
Badness
- Crowd out normal cells (fill up marrow)(dies of bleeding because don’t have platelets, anemia, infection, etc)
- Inhibit normal cell function (e.g. prevents B cells for making antibodies, etc)
- Infiltrate other organs
Down Syndrome has increased risk of getting leukemia
Clinical findings in acute leukemia
Sudden onset*** (days)
Symptoms of bone marrow failure
- Fatigue (anemic)
- Infections (not enough WBC)
- Bleeding (bad nose bleeds, etc)
Bone pain*** (expanding marrow)
Organ infiltration (liver, spleen, brain)
Laboratory findings in Acute Leukemia
- Blasts/immature cells in blood
- Leukocytosis (will see in almost ever case. These are the malignant blasts)
- Anemia
- Thrombocytopenia
Acute Myeloid Leukemia things you must know
- Malignant proliferation of myeloid “blasts” in blood, bone marrow (could be any precursor cell but usually blast)
- 20% cutoff*** for diagnosis (nucleated cells in blood or marrow everything but red cells)(another disease w/ higher blast count but in that disease may not turn into leukemia and won’t need the heavy Tx and so to separate these cases the 20% stipulation was made)(1-2% blasts is normal)
- Many subtypes
- Bad prognosis
AML “old classification”
M0 - acute myeloblastic leukemia, minimally differentiated
M1 - acute myeloblastic leukemia without maturation
M2 - acute myeloblastic leukemia with maturation
M3 - acute promyelocytic leukemia (likely to go into DIC)
M4 - acute myelomonocytic leukemia
M5 - acute monocytic leukemia (tend to have cells that crawl out so give Tc in CSF)
M6 - acute erythroblastic leukemia
M7 - acute megakaryoblastic leukemia
Based on what type of cell predominating. (all young and myeloid cells)
Revised AML “old” classification
M0, 1, 2, 3-involve neutrophilic series
(myeloblasts, promyelocytes, etc.)
M4, 5-involve monocytic series (monoblasts, etc.)
M6-involves erythroid series (erythroblasts)
M7-involves megakaryocytic series (megakaryoblasts)
How do you know when a leukemia is myeloid?
- Many times blast and can’t tell what they are
- Dysgranulopoeisis-growing funny/weird looking changes
- In AML–>auer rods***(composed of primary granules)(little sticks in cytoplasm)(many cases of AML can occur w/o auer rods)
- Cytochemistry
- Immunophenotyping
- Cytogenetics
AML “new” classification
- AML with genetic abnormalities
- AML with FLT-3 mutation
- AML with multilineage dysplasia
- AML, therapy-related (had cancer previously and got chemo and now AML. These are hard to treat)
- AML, not otherwise classified
AML-M0 things you must know
- Increased myeloblasts
- Bland
- MPO negative (stain done on cells to see if part of neutrophil series)
- Need markers (nothing else you can rely on)(need to do flow on it)
- Least differentiated of the AML series (usually 90% blasts)
AML-M1 things you must know
- Increased myeloblasts
- No/minimal maturation
- Auer rods
- MPO positive
AML-M2 things you must know
- Increased myeloblasts (not as much as 0,1)
- Maturing neutrophils
- t(8;21) in some cases (better prognosis)***
AML-M3 things you must know
- Increased promyelocytes
- Faggot cells (ton of aurer rods)
- DIC (granules that are procoagulant)
- t(15;17) in all cases***
- All trans-retinoic acid overcomes genetic defect. Removes block on promyelocytes and start maturing
AML-M4 things you must know
- Increased myeloblasts
- Increased monocytic cells
- Extramedullary tumor masses (anytime have leukemia w/ moncytic. Need to worry about monocytes getting out and need to protect CNS (intrathecal therapy) gums/skin/testes are big 4 involved.)
- inv(16) in some cases (better prognosis)
- “Like a dual leukemia”
AML-M5 things you must know
- Increased monocytic cells
- NSE positive
- M5A and M5B (one form monoblast (5A) other form chromatocytes (5B) “her favorite”)
- Extramedullary tumor masses
MPO and NSE stain what?
MPO neutrophil and precursors
NSE monocytic
AML-M6 things you must know
- Increased erythroblasts
- Increased myeloblasts
- Dyserythropoiesis
AML-M7 things you must know
- Increased megakaryoblasts (only one that involves platelet precursors)
- Bland blasts
- MPO negative
- Need markers
AML w/ genetic abnormalities (certain cytogenetic changes in AML that can give better or worse prognosis)
- t(8;21) (AML-M2) Looks different than other cases of M2. The cells get gigantic.
- inv(16) (AML-M4) Gigantic eosinophils w/ dark blue granules instead of little orangish.
- t(15;17) (AML-M3) All cases have this. (can’t give regular chemotherapy as will burst cell and release granules)
- 11q23 (something wrong w/ long arm of 11 band 2 subpart 3 (??) could be translocation, deletion, etc) Usually seen in AML w/ monocytic component.
***First three good prognosis w/ the last being bad
AML w/ FLT-3 mutation
- Mutation of FLT-3 (a tyrosine kinase)
- Present in 1/3 of cases of AML!
- Monocytic cells
- Poor prognosis (more likely to relapse, cells grow faster) (e.g. WBC 16->102 in one day hard to keep blood flowing at that high of lever)
AML w/ multilineage dysplasia (cells growing funny)
- ≥ 20% blasts + dysplasia in ≥ 2 cell lines
- Elderly
- Severe pancytopenia*** (every other leukocytosis)
- Chromosome abnormalities (5, 7)
- Poor prognosis
AML therapy-related
- Previous chemotherapy
- Alkylating agents (Busulfan) or topoisomerase II inhibitors (Etoposide)
- 2-5 years to onset
- Chromosomal abnormalities sometimes (5, 7, 11q23)
- Very hard to treat
Tx and prognosis of AML
Treatment (over ally 60% patients get into 1 complete remission but many will relapse and overall survival is low)
- Chemo
- Bone marrow transplant
Prognosis
- Dismal
- t(8;21), inv(16), t(15;17) better
- FLT-3, therapy-related worse
Myelodysplastic Syndrome (MDS)
- Problem: abnormal stem cells
- Dysmyelopoiesis
- Maybe increased blasts (never up to 20% maybe 3-10%)
- May evolve into acute leukemia
What does dysplasia look like?
- Red cells: megaloblastic nuclei, fragmentation
- Neutrophils: hypogranulation, hyposegmentation
- Megakaryocytes: small, non-lobulated cells
Clinical/lab findings, Tx, and support in MDS
- Older patients
- Asymptomatic, or BM failure
- Macrocytic anemia***
- Low-grade: support, follow.
- High-grade: be aggressive.
