Aplastic Anemia And Myelodysplastic Syndromes

Front 1

What are causes of pancytopenia?

Back 1

Aplastic anemia
Myelodysplastic syndromes
Bone marrow infiltration'
Nutritional deficiencies
Bone marrow toxins
Infections
Hypersplenism
Systemic disorders
Anorexia

Front 2

What are some bone marrow infiltrates that can cause pancytopenia?

Back 2

Leukemia
Lymphoma
Carcinoma
Granulomatous disease
Fibrosis
Congenital storage disease

Front 3

What are some nutritional deficiencies taht can cause pancytopenia?

Back 3

B12
Folic acid

Front 4

What are some bone marrow toxins that can cause pancytopenia?

Back 4

Chemo
Radiation
Chemical exposure
Alcohol

Front 5

What are some infections that can cause pancytopenia?

Back 5

HIV
EBV
Parvovirus
Hepatitis
Histoplasmosis
Tb

Front 6

What is the definition of aplastic anemia?

Back 6

Peripheral blood pancytopenia
Bone marrow hypocellularity

Front 7

When can AA occur?

Back 7

Any age!

Front 8

What are causes of acquired AA?

Back 8

Acquired (vs. inherited) are 80% of the AA cases

Of those:
Idiopathic (50%)

Also:
Meds
Toxins
Viruses
Immune disorders
Others

Front 9

What are some meds that can cause acquired AA?

Back 9

Chloramphenicol
Gold
Sulfonamides
NSAIDs
Arsenic
Antiepileptics
Clopidogrel

Front 10

What are some toxins that can cause acquired AA?

Back 10

Benzene
Alcohol
Chemo
Radiation

Front 11

What are some viral infections that can cause acquired AA?

Back 11

EBV
Non-A, B, C hepatitis
HIV
Parvovirus B19

Front 12

What are some immune disorders that can cause acquired AA?

Back 12

SLE
Transfusion associated graft vs. host disease
Eosinophilic fascitis

Front 13

What are some other causes of acquired AA?

Back 13

Paroxysmal nocturnal hemoglobinuria
Thymoma
Pregnancy

Front 14

What are the characteristics of inherited AAs?

Back 14

In the context of other symptoms
Early onset

Front 15

What's the clinical presentation of AA?

Back 15

Anemia:
Neutropenia
Thrombocytopenia

Front 16

What are some of the signs and symptoms of anemia?

Back 16

Pallor
Fatigue
Chest pain
SOB
Headache

Front 17

What are some of the symptoms of neutropenia?

Back 17

Fever
Infections

Front 18

What are some of the symptoms of thrombocytopenia?

Back 18

Bruising
Petechiae
Epistaxis
Gingival bleeding
Menorrhagia

Front 19

What labs should you order in the context of aplastic anemia?

Back 19

CBC
Reticulocyte count (is the bone marrow working?)
Bone marrow biopsy: look for the hypocellularity

Work them up to look for other potential causes

Front 20

Take a look at this:

Back 20

In AA, there is essentially NOTHING in the marrow.

Front 21

What are the grades of AA?

Back 21

Nonsevere: <30% marrow cellularity; absence of pancytopenia
Severe: Marrow < 25% OR <50% with few hematopoietic cells and pancytopenic signs
Very severe: see severe, but with ANC <.2E9

Front 22

What's the pathogenesis of aplastic anemia?

Back 22

Damage/destruction/suppression of the hematopoietic stem cell leads to a depletion of the stem cell pool-->marrow failure-->AA

Front 23

What are the mechanisms by which the pathogenesis of AA can happen?

Back 23

Direct toxic effects to the hematopoietic stem cells

Immune mediated suppression of the hematopoietic stem cell

Front 24

What's the supportive treatment for AA?

Back 24

Supportive care:
-Transfusions
-Iron chelating agents
-Antibiotics
-Growth factor support: GCSF, EPO

Front 25

What's the curative treatment for AA?

Back 25

Hematopoietic stem cell transplantation
Immunosuppressants

Front 26

What ages do you do a hematopoietic stem cell transplant for if they have AA?

Back 26

Under 45.

Try and get a matched sibling donor; otherwise you can use an unmatched.

Front 27

What's the prophylaxis used for GvHD in allogenic hematopoietic stem cell transpant (HSCT)?

Back 27

Methotrexate/cyclosporine

Front 28

What are the meds that you give to someone before a HSCT to prepare them?

Back 28

Cyclophosphamite
Antithymocyte globulin
HSC infusion

Front 29

What's the prognosis for someone who gets a HSCT with AA?

Back 29

88% survival at 8 years
32% with chronic GvHD

4% graft failure

Front 30

What are the complications following HSCT?

Back 30

Graft failure
GvHD (more common with unrelated donors)
Malignancy

Front 31

What are some complications to the immunosuppression for HSCT to cure AA?

Back 31

Serum sickness
Renal failure
HTN
Late malignancies (MDS/AML)

Front 32

How long after HSCT does it take to see a response?

Back 32

3-4 months

Front 33

What cells go awry in myelodysplastic syndrome?

Back 33

Clonal hematopoietic stem cells

Front 34

What are the findings in myelodysplastic syndrome?

Back 34

Peripheral blood cytopenias
Hyperplastic (uaully) bone marrow with dysplasia

Front 35

What are the symptoms found in myelodysplastic syndrome?

Back 35

Anemia
Neutropenic symptoms
Thrombocytopenic hemorrhage, easy bruising
Symptomatic organomegaly/LAD
Bone/joint pains
Weight loss
Night sweats

No lymphadenopathy

Front 36

What are some of the findings in the RBCs in myelodysplastic syndromes?

Back 36

Macrocytic
Nucleated RBCs
Poikilocytosis: abnormally shaped RBCs
Anisolytosis: variance in size

Front 37

What are some WBC findings in myelodysplastic syndromes?

Back 37

Pelger-Huet neutrophils; neutrophils whose nuclei are hyposegmeneted

Front 38

What is the hallmark of myelodysplastic syndrome in the RBC precursor in bone marrow?

Back 38

Megaloblastic maturation in RBC precursors: the nuclei and the cytoplasm mature at different rates; nuclei lags behind

Front 39

What are the pathologic changes in megakaryocyte development in the bone marrow in myelodysplastic syndrome?

Back 39

Multiple separate nuclei
Unilobate megakaryocytes (instead of many-lobed)
Small platelets

Front 40

Cytogenetically, how do you differentiate between myelodysplastic syndrome and aplastic anemia?

Back 40

MDS: typically show more chrosomal abnormalities

Commonly deletions/duplications; lack of translocations
-Some are better than others; some are worse

Front 41

When does myeloblastic syndrome typically occur?

Back 41

It starts showing up at around 60, peaks at 75-85

Front 42

What are some important concepts underlying myelodysplastic syndrome classification?

Back 42

Cell morphology
Blast percentage in the peripheral blood/marrow
Cytogenetic information

Different subtypes give a different prognosis

Front 43

What's the international prognosis scoring system?

Back 43

Commonly used scoring system for MDS.

Based on blast percentage, cytopenias, and karyotype information

Front 44

People who have a higher IPSS scores show what findings?

Back 44

Less survival
More progression to AML

Front 45

What are common causes of therapy-related MDS?

Back 45

Alkylating agents
Radiation exposure

Front 46

What conditions are associated with alkylating agents and radiation exposure? How long do these take to develop?

Back 46

MDS
AML

5-7 years

Front 47

What are the changes that happen in therapy-related MDS?

Back 47

Deletion/loss of chromosome 5 and/or 7

Front 48

What's the prognosis for therapy-related MDS?

Back 48

Very poor; they're going to die.

Front 49

What are the findings in chronic myelomonocytic leukemia?

Back 49

Peripheral blood:
-Absolute monocytosis > 1E9
-BCR/ABL negative
-< 20% blasts

Bone marrow:
-Dysplasia in 1 or more lineages
- < 20% blasts

Front 50

What is 5q clinical syndrome?

Back 50

Happens to females
70 years old
Isolated macrocytic anemia; quiet.

Front 51

What is the prognosis for 5q clinical syndrome?

Back 51

Great!

Front 52

What are the cellular findings in 5q clinical syndrome?

Back 52

Normal-elevated platelet counts
bone marrow erythroid hyperplasia
Hypolobulated megakaryocytes

Front 53

What are the treatments for MDS?

Back 53

Observation
Allogenic HSCT (too old, usually!)
Intensive chemotherapy
Supportive care/hematopoietic growth factors
Immunosuppression
DNA methyltransferase inhibitors
IMiDs (antiapoptosis agents)
Clinical trials

Front 54

How do you minimize transfusions in myelodysplastic syndrome?

Back 54

Erythropoiesis stimulating agents

A certain subset are more likely to respond
-Low endogenous EPO
-Low existing transfusion requirements
-Bone marrow blasts <10%

Front 55

What's the use of chelation therapy in MDS?

Back 55

Remove the iron from MDS patients who are being transfused often

Only used in patients who have a long life expectancy, anyways.

Front 56

What are some hypomethylating agents used in MDS?

Back 56

Azacitidine
Decitabine

Front 57

How do the hypomethylating agents work in MDS treatment?

Back 57

Stop methylation of the chromosome --> allow transcription of important genes

Front 58

What are indications for hypomethylating agents?

Back 58

Transfusion dependence
Neutropenic
Systemic symptoms
Large blast burden

Front 59

What are the results of using hypomethyating agents in MDS?

Back 59

50% response rate

Just prolongs life, increases quality of life

Front 60

What are the toxicities of the hypomethylating agents?

Back 60

Infection risk
Suppression of the marrow
Renal, liver toxicity

Front 61

What are indications for the immunomodulatory agents in MDS?

Back 61

Severe disease

Front 62

What are the special uses for immunomodulatory agents in MDS?

Back 62

5q deletion (think the old ladies with the indolent course) --> this is very good for them!!!

Front 63

What are the responses to the immunomodulatory agents?

Back 63

50%

Prolong life; decrease transformation to AML

Front 64

What is the response to some of the hypomethylating drugs?

Back 64

Very slow. You need to give the drug in 3-4 month cycles to assess responses.

Front 65

What are the hypomethylating agents for MDS?

Back 65

Azacitidine
Decitabine

Front 66

What are some of the the non-curative agents for myelodysplastic syndrome?

Back 66

DNA methltransferase inhibitors
Immunomodulatory agents
Chelating agents
EPO stimulators

All help with the symptoms secondary to MDS

Front 67

If someone has MDS, what should you do?

Back 67

Recommend them for a clinical trial!