MDS and BM failure

Question 1

What is Myelodysplastic syndrome?

Answer 1

Group of aquired, haematological stem cells dysorder with
1. Functionally defective blood cells in (but hypercellular) bone marrow
2. Peripheral cytopenia

Also increased risk of progression into malignancy

Question 2

What morphological features can be seen in MDS?
In
1. Neutrophils
2. Erythrocytes
3. Megakaryocyttes

Answer 2

1. Neutrophils: pelger-huet anomality and hypogranularity
2. Erytrhocytes: Most common abnormality macrocytosis, but erythroblasts in bone marrow very abnormal (sideroblastics can also occur)
3. Dysplastic megakaryocytes (small or hypeolobulated in BMI)
4. Increased proportion of blast cells (>5%)

Question 3

What is Pelger-Huet anomaly?

Answer 3

Neutrophil where two nuclei are connected with very thinck bridge (+Hyposegmentation)

Question 4

What factors carry a worse prognosis in MDS?

Answer 4

• High BLast cell %
• Poor karyotype
• Low Hb
• Low Platelets
• Low Neutrophils

Question 5

In MDS, the normal BM is replaced by clonal population of cells derived from a single mutated haematopoietic stemm cell that still proliferates but the cells mature abnormally.

In what ways is maturation abnormal?

Answer 5

1. ineffective haemopoiesis (as more haemopoietic precursurs die –> explanation for hypercellular marrow + pancytopenia)
2. Abnormal maturation = Dysplasia = myeloDYSPLASTIC syndrome

Question 6

What are the complications/ problems of Myelodysplasia?

Answer 6

1. Deterioration of Blood counts
2. Development of AML (5-50%) <1year, depending on sub-type)
3. AML from MDS has very poor prognosis, as often few/no normal stem-cells present to regenerate normal haematopoesis

Question 7

What is typical clinical presentation of Myelodysplasic syndrome?

Answer 7

Usually due to cytopenia, depedant on the cell-lineage involved
1. Erythrocytes: breathlessness, anemaia, pallor
2. WCC: infections
3. Platelets: petechiae

Question 8

What do pattients with melodysplasia die of?

Answer 8

Complication of cytopenias
* haemorrhoage
* infection etc

or progression to AML

Question 9

What are curative treatment options of MDS?

Answer 9

Only curative treatment if BM transplant

potentailly intenstive chemotherapy

Question 10

What is supportive treatment options for MDS?

Answer 10

1. Blood product support
2. Antimicrobial therapy
3. Growth factors (Epo, G-CSF, TPO-Receptor Agonist)

Question 11

What disease-modyfing medications can be used in the management of MDS?

Answer 11

1. Immunosuppressive therapy
2. e.g. Lenalidomide for specific sub-type of MDS (due to 5q)
3. Oral chemotherapy: hydroxyurea if High WCC (but WCC usually low in MDS )

Question 12

What place does Chemotherapy play in the treatment of MDS?

Answer 12

Minority of patients, as mainly disease of the elderly and intensive chemotherapy not indicated

Question 13

What are primary causes of Bone Marrow Failure?

Answer 13

1. Genetic Mutations (e.g. Fanconi Anaemia)
2. Haematological diseases

Question 14

What are causes of secondary BM failure?

Answer 14

1. BM infiltration (Haematological, non-haematological)
2. Radiation
3. Drugs
4. Chemicals (benzenes)
5. Autoimmune
6. Infections (Parvovirus, Viral Hepatitis, HIV)

Question 15

What drugs cause BM failure?

Answer 15

Question 16

What are the characteristics of aplastic anaemia?

What is the most common Aetiology?

Incidence

Answer 16

1. 1/500.000
2. Peak incidence 15-24 and >60

Aetiology

70% idiopathics
inherited
* Dyskeratosis congenita, Fanconi anaemia, Schachman-Diamond syndrome

Secondary e.g. malignant infiltration, radiation, chemo

Question 17

What is the pathophysiolofy of idiopathic Aplastic anaemia?

Answer 17

Failure of BM to produce blood cells: usually problem in stem cells (CD 34) and often auto-immune

Question 18

How is aplastic anaemia diagnosed?

Answer 18

1. Blood count: cytopenia (AA= erythrocytes but can have other cytopenias)
2. BM aspirate BM: Hypocellular

Question 19

What are some diffrentials for Pancytopenia and Hypocellular Marrow?

Answer 19

1. Aplastic anaemia
2. Hypocellular ALL
3. Hypoplastic MDS /AML
4. others very rare

Question 20

What are the Camitta criteria for diagnosis of Aplastic anaemia?

Answer 20

Need 2/3 of periheral blood features
1. Low reticulocytes
2. Low Neutrophils
3. Low Platelets

AND
Bone Marrow: <25 % cellular

Question 21

How is BM failure managed?

Answer 21

1. Treat cause
2. Supportive: Blood product support, ABX +/- iron chelation
3. Biological stimmulants (EPO, TPO receptor agonist)
4. Immunosuppression in auto-immune causes
5. Stem cell transplant

Question 22

What are treatment option for Idiopathic AA?

Answer 22

1. Immunosuppression
2. Androgens
3. Stem Cell transplant: generally for patients <40 years (prognosis with sibling donor: >70%)

Question 23

What are complications of immunosuppression in idiopathic AA?

Answer 23

1. Relapse (35%)
2. Clonal Haematological disorders
3. Sold tumour risk ~3%

Question 24

What is Fanconi anaemia?

Answer 24

Most common cause of inherited aplastic anaemia

Autosomal recessive or X-linked inheritence of DNA cross-link repair defect

Several genes are associated with it

Question 25

What is the clinical presentation of Fanconi anaemia?

Answer 25

Haematology: Pancytopenia + normocytic or macrocytic anaemia, Other abnormalities in 70% MSK: short statue, raidal and thumb abnormalitie Others: renal, caé au lait spots etc. 50% risk of AML or Myelodysplastic syndrome in early adulthood

Question 26

What is Dyskeratosis congenita?

Answer 26

Inherited dysorder or telomere repair characterised by Abnormality * Abnormal skin pigmentation * Nail dystrophy * Leukoplakia + 85% have **Bone Marrow failure**

Question 27

What is the prognosis of Fanconi anaemia?

Answer 27

Overall poor prognosis --> severe aplastic anaemia will often kill most people before the age of 10

Question 28

What is the comparison between Dyskeratosis Congenita and idiopathic aplastic anaemia?

Answer 28

Clinically similar But no somatic features in aplastic canemia

Question 29

What is the epidemiology of Myelodysplastic syndrome?

Answer 29

Usually idiopathic in middle-aged and eldery patients (Might be secondary to cytotoxic chemoatherapy in younger patients)

Question 30

What is the difference between MDS and Myeloid Leukaemia?

Answer 30

Both have * replacement of normal bone marrow by clonal cells but * % of blast cells different * >5% in MDS * >20% in AML MDS is not yet classified as a AML/ CML (however now classified as malignant) but can lead to disease progression and tranformation to AML