AML and MDS - Krafts Flashcards by Erin Mustonen

What is AML?

Acute Myeloid Leukemia

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What is MDS?

Myelodysplastic Syndrome

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Acute Leukemia characteristics

Sudden onset
Adults or Children
Rapidly fatal without treatment
Immature cells (blasts)

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Chronic Leukemia characteristics

Slow onset
ONLY in adults (>40)
Longer course
Mature cells

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What is ALL?

Acute Lymphoblastic Leukemia

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What is CLL?

Chronic Lymphocytic Leukemia

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What is CML?

Chronic Myeloid Leukemia

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What is the definition of Acute Leukemia?

Malignant proliferation of immature myeloid or lymphoid cells in the blood or bone marrow

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What causes Acute Leukemia?

Clonal Expansion
Maturation Failure (Arrest)
Usually idiopathic
Genetic disorders can predispose patients (Down's Syndrome)
Sometimes caused by toxins (Benzenes)

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What is so bad about Acute Leukemia?

Crowds out normal cells
Inhibits normal cell function (making immunoglobulins)
Fill up marrow space
Infiltrate other organs

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Describe Acute Leukemia bone marrow

Normal Marrow space filled with many malignant cells

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Bone Marrow Failure in Acute Leukemia symptoms

Fatigue
Infections
Bleeding

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What symptoms are associated with Acute Leukemia?

Sudden onset
Bone Marrow Failure
Bone Pain (expanding marrow of long bones)
Organ Infiltration (liver, spleen, brain)

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What are the laboratory findings for Acute Leukemia?

Leukocytosis
Anemia
Thrombocytopenia
Blasts/immature cells in blood

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Acute Myeloid Leukemia Characteristics

Malignant proliferation of myeloid blasts in blood and bone marrow
20% blast cutoff for diagnosis
Poor prognosis

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How do you know when a leukemia is myeloid?

Dysgranulopoiesis
Auer Rods
Cytochemistry
Immunophenotyping
Cytogenetics

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What is dysgranulopoiesis?

Nucleus is not segmented and cytoplasm is devoid of granulation

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What are Auer rods?

Thin, purple rods composed of primary granules

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Where would you find Auer rods?

Malignant, Myeloid Blast cells

How would you determine myeloid leukemia using cytochemistry?

Stain with non-specific esterase (turns orange)

AML-M0

Acute Myeloblastic Leukemia, Minimally Differentiated

HIGH number of myeloblasts
Bland blasts = no Auer rods, no granulation
Myeloperoxidase negative
Need markers on cell surface for diagnosis = via FLOW cytometry

AML-M1

Acute Myeloblastic Leukemia without Maturation

HIGH number of myeloblasts
No maturation (ALL Blasts)
Auer Rods
Myeloperoxidase positive

AML-M2

Acute Myeloblastic Leukemia with Maturation

Increased number of myeloblasts
Some maturing neutrophils
Some cases have special translocation t(8;21) = better outcome

AML-M3

Acute Promyelocytic Leukemia

HIGH number of promyelocytes
Faggot cells with a TON of Auer rods
DIC (Disseminated Intervascular Coagulation)
ALL cases have translocation t(15;17) = good prognosis

What is the t(15;17) translocation involved in?

Retinoic Acid Receptor | Treat with All-Trans Retinoic Acid

M0, M1, M2, M3 Acute Myeloid Leukemias

Involve Neutrophilic Series | Myeloblasts, Promyelocytes

AML-M4

Acute Myelomonocytic Leukemia ``` Increased myeloblasts (20%) and monocytic cells Extramedullary Tumor Masses Some cases have translocation inv(16) = better prognosis ```

AML-M5

Acute Monocytic Leukemia Increased monocytic cells Non-Specific Esterase Positive Two Types: M5A and M5B Extramedullary Tumor Masses

M4 and M5 Acute Myeloid Leukemias

Involve Monocytic Series | Monoblasts

AML-M6

Acute Erythroblastic Leukemia Increased Erythroblasts and Myeloblasts Dyserythropoiesis

M6 Acute Myeloid Leukemia

Involves Erythroid Series | Erythroblasts

AML-M7

Acute Megakaryoblastic Leukemia Increased Megakaryoblasts Bland blasts Myeloperoxidase Negative Need cell surface markers for diagnosis via FLOW cytometry

M7 Acute Myeloid Leukemia

Involves Megakaryocytic Series | Megakaryoblasts

AML, not otherwise classified

AML - M0 through M7

AML with Genetic Abnormalities

Good Prognosis: AML-M2 with t(8;21) AML-M4 with inv(16) AML-M3 with t(15;17) Poor Prognosis: AML-Monocytosis with 11q23

AML with FLT-3 Mutation

Mutation of FLT-3 (a tyrosine kinase) Present in 1/3 of cases of AML! Monocytic cells Poor prognosis

AML with Multi-Lineage Dysplasia

``` ≥ 20% blasts + dysplasia in ≥ 2 cell lines Elderly Severe pancytopenia Chromosome abnormalities Poor prognosis ```

AML Therapy-Related

Previous chemotherapy from Alkylating Agents (Busulfan) or TOPO II inhibitors (Etoposide Onset is 2-5 years after chemo EXTREMELY HARD TO TREAT!

Treatment for AML

Chemotherapy and Bone Marrow Transplant (Curative)

Prognosis for AML

Not good Better in children than adults Better: t(8;21) t(15;17) inv(16) Worse: FLT-3 Therapy-Related

Myelodysplastic Syndrome

Problem: abnormal stem cells Dysmyelopoiesis Maybe more blasts May evolve into acute leukemia

What does dysplasia of Red Cells look like?

Megaloblastic nuclei with fragmentation

What does dysplasia of Neutrophils look like?

Hypogranulation and Hyposegmentation

What does dysplasia of Megakaryocytes look like?

Small, non-lobulated cells

Clinical Findings in MDS

Older patients Asymptomatic or Bone Marrow Failure Macrocytic Anemia