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_MS2 HemeOnc > 8/13- MDS/AML > Flashcards

8/13- MDS/AML Flashcards

1
Q

What is MDS?

A

Myelodysplastic Syndrome

  • Aka “refractory anemia”, “preleukemia”, or “smoldering leukemia”

Spectrum of clonal myeloid disorders characterized by:

  • Ineffective hematopoiesis
  • Cytopenias
  • Qualitative disorders of blood cells
  • Clonal chromosomal abnormalities
  • Variable tendency to evolve into acute leukemia
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2
Q

Can divide/organize MDS how? (dkfjadj)

A
  • “Clonal bicytopenia or tricytopenias”
  • “Oligoblastic leukemia”
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3
Q

Epidemiology of MDS?

A

Most common clonal hematologic disorder

  • 1-10/100,000 /year in Western countries
  • 3,000-12,000 cases/year in US

Disease of the elderly – incidence increases logarithmically after the age of 20

Men affected more than women (1.5x)

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4
Q

Pathogenesis of MDS?

A

Clonal expansion of a multipotential hematopoietic cell

Chromosomal deletions or additions involving most frequently:

  • Long arms (q) of chromsomes 5 and 7
  • Del of 5 and 7
  • Del of 11, 12, 13, 20
  • Trisomy 8

Major mechanism is ineffective hematopoiesis: defective maturation and death of marrow precursor cells.

  • Decreased production/sensitivity to hematopoietic growth factors
  • Increased production of hematopoietic inhibitors (TNFa, Ifng) inducing apoptosis
  • T-cell mediated immune dysregulation
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5
Q

Risk factors for MDS?

A

Radiation Drugs and toxins

  • benzene and other solvents
  • alkylating agents (-5, -7)
  • topoisomerase II inhibitors (11q23)
  • smoking
  • hair dyes
  • pesticides, herbicides, organic chemicals

Other hematologic disorders

  • aplastic anemia, paroxysmal nocturnal hemoglobinuria, congenital neutropenia

Genetic disorders

  • Down syndrome Fanconi’s anemia,
  • Neurofibromatosis (von Recklinghausen’s disease)
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6
Q

Clinical Manifestations of MDS?

A
  • Anemia: weakness, fatigue, palpitations, orthostasis
  • Thrombocytopenia: bleeding, bruising
  • Leukopenia: increased susceptibility to infection
  • Other: Sweet disease, polyarthritis, neuropathy, acquired alpha thalassemia, splenomegaly
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7
Q

DDx of MDS?

A
  • Drugs or toxic exposures
  • Infections
  • Rheumatic disorders
  • Deficiencies of vitamins B12, B6, or folic acid
  • Hypersplenism
  • Metastatic cancer
  • Acute leukemia
  • Aplastic anemia
  • Paroxysmal nocturnal hemoglobinuria
  • Myelofibrosis
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8
Q

What are features of the PBS in MDS?

A

Red cells:

  • Anisocytosis
  • Normocytic or mildly macrocytic indices
  • Low reticulocyte count
  • Howell-Jolly bodies, Cabot rings, basophilic stippling

White cells:

  • Small, poorly granulated neutrophils with hyper- or hypolobulated nuclei
  • Increased monocytes

Platelets:

  • Large, agranular
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9
Q

What is shown here?

A

Pseudo Pelger-Huet cell

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10
Q

What is shown here?

A

Stodtmeister cell

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11
Q

What is shown here?

A

A: Basophilic stippling

B: Howell-Jolly bodies

C: Cabot’s rings

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12
Q

Overview of bone marrow in MDS?

A
  • Erythroid Dysplasia
  • Myeloid Dysplasia
  • Megakaryocytic Dysplasia
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13
Q

What is shown here?

A

MDS

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14
Q

What is shown here? Condition/features? Prognosis?

A

Refractory Anemia

  • Dimorphic population
  • Less than 5% blasts in marrow
  • AML in 10% at 2 yrs
  • Median survival 3-6 yrs
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15
Q

What is shown here? Conditions/features? Prognosis?

A

Refractory Anemia with Ringed Sideroblsats

  • > 15% ringed sideroblasts
  • Less than 5% blasts in marrow
  • AML in 0% at 2 yrs
  • Median survival: 3-6 yrs
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16
Q

MDS is associated with what genetically?

A

Isolated del(5q)

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17
Q

Epidemiology of MDS?

A
  • Occurs primarily in middle-aged women
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18
Q

Characteristics of MDS?

A
  • Characterized by macrocytic anemia and normal or increased platelet count
  • Megakaryocytes with hypolobulated nuclei
  • Favorable clinical course with absence of leukemic transformation
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19
Q

International Prognostic Index (IPI) for MDS?

A
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20
Q

Standard treatment of MDS?

A

Supportive care:

  • Erythropoietin, G-CSF, GM-CSF, IL-11
  • Blood transfusion
  • Deferoxamine or Exjade (iron chelator)
  • Pyridoxine, folic acid
  • Danazol Immunomodulation
  • Antithymocyte globulin
  • Cyclosporine
  • Steroids

AML-style chemotherapy

Newer agents affecting DNA methylation

Bone marrow transplantation

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21
Q

What are 5-zacytidine (Vdiaza) and Decitabine (Dacogen)?

Response?

Side effects?

A
  • Vidaza is prodrug for Decitabine, which reduces DNA methylation at cytosine residues and allows reactivation of silenced tumor-suppressor genes (demethylating agents)
  • Overall response rate 16-17% (CR 7%, PR 16%, improvement in 37%)
  • Significant side effects including cytopenias, GI disturbances, fever, fatigue and various aches and pains
22
Q

Organization/Division of the Leukemias?

A
23
Q

Acute leukemias are a group of disorders characterized how?

A
  • Neoplastic transformation of hematopoietic stem cell (Clonality)
  • Malignant cells either do not differentiate or differentiate abnormally
  • Abnormal cells accumulate in blood, marrow and tissues
  • Normal hematopoiesis is inhibited
  • Fatal if untreated
24
Q

Relative frequency of leukemias?

A

CLL: 32%

AML: 30%

ALL: 13%

Other: 13%

CML: 125

25
Q

TEST TEST TEST

What is shown here?

A

AML! Acute Myelogenous Leukemia

BE ABLE TO RECOGNIZE THIS

  • Can see Auer rods!
26
Q

Epidemiology of AML?

Percentage of acute leukemias in adults/children?

A
  • 15-20% of acute leukemia in children
  • 80% of acute leukemia in adults
  • 12,000 new cases/yr in the US
  • 8,000 deaths/yr in US
  • Median age is 63 (Disease of the elderly!)
27
Q

Risk factors for AML?

A

Genetics:

  • Chromsomal abnormalities: Down’s, Klinefelters
  • Chromsomal instability: Fanconi’s anemia, Bloom’s

Prior chemotherapy:

  • Alkylating agents: Cyclophosphamide, Mechlorethamine
  • Topoisomerase II inhibitors: Etoposide, Anthacyclines

Radiation exposure: Hiroshema survivors, Radiologists (before modern shielding)

Environmental exposure: benzene

Prior hematologic abnormalities: Myelodysplasia, MPNs

28
Q

What is shown here?

A
29
Q

WHO/FAB Classification of AML?

A

AML with genetic abnormalities

  • t(8;21) or inv (16)
  • 11q23 abnormalities
  • APL with t(15;17) AML with multilineage dysplasia
  • Evolution from MDS
  • No MDS, but dysplasia in 2 or more cell lines AML secondary to therapy
  • Radiation/alkylating agent
  • Topoisomerase II inhibitor AML NOS (FAB classification)
30
Q

FAB Classification of AML?

A
31
Q

M2 (AML with maturation) is associated with what translocation?

A

t(8:21)

32
Q

M3 (Acute promyelocytic leukemia) is associated with what translocation?

A

t(15:17)

33
Q

M4 (Acute myelomonocytic leukemia) is associated with what translocation?

A

inv 16

34
Q

Clinical Presentation of AML?

A

Cytopenias:

  • Anemia (fatigue)
  • Leukopenia (infection/fever)
  • Thrombocytopenia (bleeding)

Hyperleukocytosis: increased risk of CNS involvement

  • Leukostasis (blast count > 50-100K, limited flexibility of blasts, lungs/brain most affected)

Extramedullary disease:

  • Gums with M4/M5
  • Chloromas with M2
  • CNS Coagulopathy
  • DIC, especially with M3 (also M4 and M5)
35
Q

Petechiae are usually indicative of what abnormality?

A

Low platelet count

36
Q

What is shown here?

A

Hyperleukocytosis in pt with M4

  • HUGE buffy coat!
37
Q

Which form of AML is associated with gum infiltration?

A

M5

38
Q

Which form of AML is associated with M3?

A

DIC Ex)

  • Platelets 5,000
  • Fibrinogen 25
39
Q

CNS hemorrhage may occur in pt with what form of AML?

A

M3 (from DIC)

  • Most feared complication (bleed before you can treat the leukemia)
40
Q

CNS leukemia may cause what nerve complications?

A

CN VII palsy (Bell’s palsy)

41
Q

Diagnosis of AML?

A

Bone marrow exam

  • Wright-Giemsa stain
  • Sudan/special stains
  • Flow cytometry (aspirate)
  • Cytogenetics (aspirate)
  • Molecular rearrangements
42
Q

Cytogenetics and prognosis in AML?

A

Good prognosis:

  • t(8:21)
  • inv(16)
  • t(15:17)

Intermediate:

  • Normal

Poor:

  • del 5/5q or 7/7q
  • Abnormalities of 11q23
  • Multiple abnormalities
43
Q

What is the most common subtype of AML?

  • Genetics?
  • Prognosis?
A

M2 AML (AML with maturation)

  • 50% have t(8:21)
  • Better prognosis than average
44
Q

What demographic groups are most commonly affected by M3 AML?

  • Genetics?
  • Prognosis?
  • Treatment?
A

M3 AML (Acute Promyelocytic Leukemia/APL)

  • Seen in younger Hispanic pts
  • May see Auer rods or big chunky granules in PBS (emergency!) 80-100% have t(15:17)

Risk of DIC: bleeding, thrombosis

Unique treatment: all-trans-retinoic acid

45
Q

What is this?

A

M2 AML, t(8:21)

46
Q

What is this?

A

M3 AML

  • May see Auer rods or big chunky granules (emergency!)
47
Q

What is shown here?

A

Abnormal cell with t(15:17) on FISH

  • Indicative of M3 AML
48
Q

Treatment of AML? Complications? Maintenance therapy?

A

Induction chemotherapy:

  • Anthracycline plus
  • Cytarabine

Complications:

  • Prolonged neutropenia
  • infection
  • Prolonged thrombocytopenia

Consolidation chemotherapy

No maintenance except M3

Bone marrow transplantation

49
Q

Treatment of APL (M3 AML)?

A

ATRA (all transretinoic acid) + Chemotherapy

or

ATRA + Arsenic

(ATRA can put pts into remission, but doesn’t keep them there; not enough)

50
Q

Prognosis of AML for children? Adults?

A

Children:

  • 90% complete remission
  • 40% long-term cure rate

Adults:

  • 65-70% complete remission
  • 30% long-term cure
51
Q

Adverse prognostic factors in AML?

A
  • Age > 60 yo
  • Poor risk cytogenetics
  • Antecedent hematologic disorder
  • WBC > 100K
  • Presence of multidrug resistance gene 1 (MDR)
  • Failure to achieve complete remission with first cycle

_MS2 HemeOnc (33 decks)

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