AML and MDS - Krafts Flashcards
What is AML?
Acute Myeloid Leukemia
What is MDS?
Myelodysplastic Syndrome
Acute Leukemia characteristics
Sudden onset
Adults or Children
Rapidly fatal without treatment
Immature cells (blasts)
Chronic Leukemia characteristics
Slow onset
ONLY in adults (>40)
Longer course
Mature cells
What is ALL?
Acute Lymphoblastic Leukemia
What is CLL?
Chronic Lymphocytic Leukemia
What is CML?
Chronic Myeloid Leukemia
What is the definition of Acute Leukemia?
Malignant proliferation of immature myeloid or lymphoid cells in the blood or bone marrow
What causes Acute Leukemia?
Clonal Expansion Maturation Failure (Arrest) Usually idiopathic Genetic disorders can predispose patients (Down's Syndrome) Sometimes caused by toxins (Benzenes)
What is so bad about Acute Leukemia?
Crowds out normal cells
Inhibits normal cell function (making immunoglobulins)
Fill up marrow space
Infiltrate other organs
Describe Acute Leukemia bone marrow
Normal Marrow space filled with many malignant cells
Bone Marrow Failure in Acute Leukemia symptoms
Fatigue
Infections
Bleeding
What symptoms are associated with Acute Leukemia?
Sudden onset
Bone Marrow Failure
Bone Pain (expanding marrow of long bones)
Organ Infiltration (liver, spleen, brain)
What are the laboratory findings for Acute Leukemia?
Leukocytosis
Anemia
Thrombocytopenia
Blasts/immature cells in blood
Acute Myeloid Leukemia Characteristics
Malignant proliferation of myeloid blasts in blood and bone marrow
20% blast cutoff for diagnosis
Poor prognosis
How do you know when a leukemia is myeloid?
Dysgranulopoiesis Auer Rods Cytochemistry Immunophenotyping Cytogenetics
What is dysgranulopoiesis?
Nucleus is not segmented and cytoplasm is devoid of granulation
What are Auer rods?
Thin, purple rods composed of primary granules
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
