MDS

Question 1

What is MDS?

Answer 1

Neoplastic bone marrow due to dysplasia of one or more myeloid cell lines.
This then results in peripheral cytopenia.

Question 2

Briefly, what does the WHO classification do?

Answer 2

Brings together information from morphology, immunophenotyping, genetics and clinical features to define the type of disease.

Question 3

What is a difficulty of diagnosing MDS?

Answer 3

Dysplasia of cells can also be reactive/caused by other things such as:

• nutritional deficiency (vitamin B12)
• infections
• toxins.

These causes must be ruled out.

Question 4

Who gets MDS? What causes it?

Answer 4

Typically older generation, median age 70yrs.

Can be de novo (accumulation of damage over time) or can be a result of previous therapy/treatment with chemotherapy or radiation.

Question 5

What are the WHO 2016 classification groups for MDS?

Which entry is provisional?

Answer 5

Single lineage dysplasia
Multi lineage dysplasia
MDS with ringed sideroblasts (RS)
MDS-RS with single lineage dysplasia
MDS-RS with multi lineage dysplasia
MDS with excess blasts
isolated del5q
Unclassifiable

Provisional: refractory cytopenia of childhood.

Question 6

Which is the only type of MDS to be defined by a cyto abnormality?
Who does it more commonly affect? What is it’s prognosis?

Answer 6

MDS with isolated del5q.
Predominately affects mid-older women.
It has a good prognosis with long survival/low risk of transformation.

Question 7

In ‘isolated 5q syndrome’, if 1 additional abnormality is seen does this change the prognosis?

Answer 7

No - as long as it isn’t either -7 or del7q.

Question 9

What are ringed sideroblasts? What percentage need to be seen to change the type of MDS diagnosed?

Answer 9

Erythroid precursors.

Need to see >15% (unless there is a SF3B1 mutation)

Question 10

What are Auer Rods? What do they mean?

Answer 10

Crystallline inclusions seen in myeloblasts.

They are always pathological.

Question 11

What is the name of the treatment routinely used in patients with del5q MDS?

Answer 11

Lenolidamide.

Question 12

What is the general pattern of abnormality rate in MDS?

Answer 12

The percentage of cases with cytogenetic abnormalities increases with the severity of the disease and transformation.

Question 13

What is clonal evolution in the context of MDS?

Answer 13

The presence of new abnormalities that weren’t there at diagnosis:

• additional abs
• normal karyotype at diagnosis but now has cyto abs.

Question 14

How does an MDS transform into a leukemia?

Answer 14

Additional hits to the genome cause further disarray within haematopoiesis and can cause maturation block = blast count increases and disease becomes leukemic.

Question 15

What is the approx. abnormality rate in MDS?

Answer 15

30-50%

Question 16

What abnormalities are typical seen in MDS? Give some examples?

Answer 16

Generally involves gain or loss of genetic material.

del(5q)/-5 and del(7q)/-7
+8
Del 20q
Complex karyotypes with various abnormalities.

Question 17

What I the IPSS-R? What are the subgroups and their associated risk score? What is the score use for?

Answer 17

The revised scoring system for assessing the prognosis of patients with MDS based on a number of disease features including cytogenetic abnormalities detected, blast count and cytopenias.

5 subgroups. Very good (0), good (1), intermediate (2), poor (3), very poor (4).

It is added to things like the BM blast score to give the patient an overall ‘total’ score that predicts their prognosis including median expected survival.

Question 18

What abnormalities when seen alone are classed as ‘very good’?

Answer 18

-Y or del(11q)

Question 19

What abnormalities are classed as ‘good’?

Answer 19

Normal K
del(5q) either alone or with single abn
del(20q)
del(12p)

Question 20

What abnormalities are classed as ‘intermediate’?

Answer 20

del(7q)
\+8
\+19
i(17q)
Any other single or double abn clone.

Question 21

What abnormalities are classed as ‘poor”?

Answer 21

-7
inv(3)/del(3q)/t(3q)
double abn if it involves a 7 (del or monosomy)
Complex clone with exactly 3 abnormalities.

Question 22

What abnormalities are classed as ‘very poor’?

Answer 22

Complex clone with >3 abnormalities.

Question 23

What challenge does -Y present when seen alone?

Answer 23

It could represent age related loss especially given the age of MDS patients.

Generally -Y in MDS is much higher than in age related loss.

Question 24

What would we do if a karyotype fails in an MDS patient?

What should we bare in mind though with regards to the WHO classification?

Answer 24

FISH using EGR1/D5S23 and CEP7/D7S486 which will detect either complete loss or deletions of the long arms of chromosomes 5 and 7.

It may also detect any structural abnormalities involving these chromosomes.

MDS defining abnormalities must however be identified by metaphase analysis though to be used to define MDS in a cytopenic patient (in the absence of dysplasia)

Question 25

List some abnormalities that are sufficient (according to the WHO 2008 and reiterated in 2016) for a diagnosis of MDS when cytopenia is present.

Answer 25

Unbalanced:
-7 or del(7q)
-5 or del(5q)
i(17q) or t(17p)
-13 or del(13q)
del(11q)
del(12p) 
del(9q)
idic(X)

Balanced:
Several translocations including multiple which involve chr3. If found would check WHO for list.

Question 26

How many cells should be analysed in an abnormal diagnostic MDS?

Answer 26

5 analysed and 5 checked.

Question 27

How many cells should be analysed in a normal MDS?

Answer 27

20 cells: 10 analysed and 10 checked.