The term “myelodysplasia” comes from the Greek words: “myelo”, ie blood cells, and “dysplasia”, ie abnormal development or growth.

Myelodysplastic syndromes (MDS) are a heterogeneous group of blood pathologies where bone marrow cells can not become perfect and healthy cells but stop at an immature stage. The bone marrow therefore fails to produce enough red blood cells, white blood cells or healthy platelets.

These cells that remain at an immature stage are called “blasts”

The incidence of this disease in Europe is about 8 people per 100,000 inhabitants. It is a disease affecting mainly elderly people: over 70, people affected by MDS are about 35 people per 100,000 inhabitants.

Most experts agree that myelodysplastic syndromes are a type of bone and bone marrow cancer that can occur in either chronic or aggressive form.

It is not a hereditary or contagious pathology.

Myelodysplastic syndromes are defined as “clonal” diseases because the development of the disease is due to a single cell that, escaping control mechanisms, multiplies which results in the production of altered cells in form and function  that receive the “defect” from the cell progenitor.


The symptoms and the development  change considerably from patient to patient, depending on the type of affected blood cell: there may be anemia (caused by red blood cell reduction), neutropenia (when neutrophils decrease) and / or thrombocytopenia (ie platelet reduction).


In the most serious cases MDS can evolve in acute myeloid leukemia.

The causes of most MDS are unknown. We know that one of the bone marrow stem cells undergoes DNA alterations and begins to produce abnormal cells that fail to complete their maturation to become blood cells or otherwise fail to survive for a long time. However, the mechanism for this process is not known.

There are, however, forms of so-called “secondary  MDS” that may occur in people who have been exposed to certain chemicals such as benzene, lead, or have  had chemotherapy previously or have been exposed to radiation.

For some patients, the discovery of myelodysplasia is not associated with the presence of particular symptoms, the disease is occasionally detected by blood tests for other reasons.

Often, however, patients have symptoms due to the lack of red blood cells, white blood cells, and / or platelets.

The most frequent symptoms are related to anemia (red blood cells lower than normal):


Poor levels of attention and concentration

Loss of appetite or weight loss

Skin paleness

Shortness of breath

Rapid heartbeat



Low white blood cell levels may cause:

Recurrent infections

Sense of fatigue and loss of energy

Mouth  ulcers

Periods of prolonged illness


Low platelet levels could cause:

Increased susceptibility to bleeding and ecchymosis even after small blows or scratches


Bleeding gums.

To get a correct diagnosis of myelodysplasia, numerous tests are needed to allow the physician to better identify the disease.

  • Blood tests: This is the first exam that the doctor normally prescribes to further investigate the patient’s state of illness (but, as explained above, myelodysplasia may not be associated with symptoms and be occasionally discovered following routine or specialized blood tests). The investigation usually includes blood count, leukocyte formula and any other parameters such as EPO dosage, iron, vitamin B12 and folate levels
  • Bone marrow aspiration: If the results of blood tests indicate anemia, neutropenia, and / or thrombocytopenia, the bone marrow examination will be performed. In this examination, the doctor removes some liquid bone marrow (called medullary blood) with a hollow needle that will be then examined with the microscope to verify the percentage of blasts and dysplastic blood cells. The exam is normally done as an outpatient procedure.
  • Bone marrow biopsy (BMB): This is a sampling through a needle of a bone marrow fragment. This exam is used to evaluate the number of different types of blood cells, their maturation level, and the presence of foreign cells. Bone marrow aspiration and bone marrow biopsy offer different and complementary information. The exam  is usually performed as an outpatient procedure.  The doctor often decides to do the bone marrow aspiration and the BOM at the same time. In some cases it may instead decide to do only the bone marrow aspiration.
  • Cytogenetics: This exam allows to study cell chromosomes and to verify  if there are any alterations that may help identify myelodysplasia and therapy. It is performed on the bone marrow  smear.
  • FISH: It is not a routine examination in karyotyping but is prescribed only when the physician has specific diagnostic suspects or to further examine certain cytogenetic anomalies. It is an examination characterized by a higher degree of resolution because it allows the physician  to characterize number and structure  chromosomal abnormalities that can not be defined by the classical cytogenetics technique and to clarify dubious situations.
  • Cytofluorimetry: It is a laboratory test consisting in the analysis of bone marrow blood cells by providing a detailed summary of the types and levels of cells in the bone marrow

Myelodysplastic syndromes are divided into subtypes based on the results of blood and bone marrow tests.. Prognostic scores (IPSS and IPSS-r) were created to determine the risk class to which myelodysplasia belongs and the possibility of evolution in acute leukemia.

The risk tables that have been used as reference, starting from the FAB (French American British Classification System), which dates back to 1982, to the WHO (World Health Organization Classification System) of 2002 are shown below.


FAB Classification

RA ( Refractory Anemia) <1 <5
RARS ( Refractory Anemia with Ring Sideroblasts) <1 <5
RAEB ( Refractory Anemia with Excess  Blasts) <5 5-20
RAEB- t ( Refractory Anemia with Excess  Blasts in Transformation) >5 21-30
CMML (  Chronic MyeloMonocytic Leukemia ) >5 5-20


WHO Classification

This classification ( introduced in 1999 and revised in 2008) expands the one proposed by the old FAB but defines more precisely some subtypes

It distinguishes 6 main forms:

RCUD ( Refractory Cytopenia with Unilineage Dysplasia):

    1. AR (Refractory Anemia)
    2. RN (Refractory Neutropenia)
    3. RT (Refractory Trombocytopenia)
    1. Low levels of red blood cells that can’ be treated with iron or vitamines
    2. Low white cells count
    3. Low levels of platelet

<5% of blasts

  1. Red blood cells dysplasi
  2. White cells dysplasia
  3. Megacariocyte dysplasia
RARS (Refractory Anemia with Ring Sideroblasts) More than 15% of red blood cells contains ring-shaped iron deposits ( ring sideroblasts)
RCMD ( Refractory Cytopenia with Multilineage Dysplasia) Low white blood cells count ( neutropenia) or platelet count (Trombocytopenia) Dysplasia in more than 1 cell type < 5% of blasts
RAEB 1 (Refractory Anemia with Excess  Blasts) Normal number of blasts in blood 5-9% of blasts
RAEB 2 ( Refractory Anemia with Excess  Blasts) There could be blasts in blood 10-19% of blasts
5q-isolated deletion Same criteria of  Refractory Anemia, plus a normal or high platelet count Deletion of chromosome 5q without other chromosomic abnormalities
MDS U (Unclassified MDS) Low count of platelet or white blood cells Unusual features, such as scarring (fibrosis) of the bone marrow


The principal differences between FAB classification and  this one are:

  • The RAEB-t subtype was excluded and included in the  the category of acute myeloid leukemia
  • CMML subtype was excluded and included  in a group of pathologies with  features of myelodysplastic syndromes and myeloproliferative disorders (MDS / MPN)
  • A new subtype was introduced, the isolated 5q-
  • The RAEB category was divided into two groups, RAEB-1 and RAEB-2, depending on the number of blasts in the marrow or peripheral blood (5-9% the first and 10-19% the second)

The set of clinical and biological data at the time of diagnosis provides prognostic indications that can be used to establish the best therapeutic strategy for the individual patient, how quickly myelodysplasia could progress and how could be the disease evolution.

It is important to establish it at the time of the diagnosis and before starting the therapy, which can also be selected on the results of the score (due the treatment, the score could change over  the time ).



It was introduced in 1997 and its calculation is based on 3 factors:

  1. Cytogenetic results
  2. Cytopenia ( low count of red blood cells, white blood cells and / or platelets)
  3. Percentage of blasts in the bone marrow

For each factor is assigned a score, the sum of these scores provides the IPSS score for the specific case.

Factor Value IPSS Score
Blasts in bone marrow less than 5% 0
5% to 10% 0.5
11% to 20% 1.5
21% to 30% 2.0
Cytogenics Good 0
Intermediate 0.5
Poor 2.0
Low blood counts or cytopenias 0 or 1 cytopenia 0
2 o 3 cytopenia 0.5


0 Low Risk
0.5-1 Intermediate 1 Risk
1.5-2 Intermediate 2 Risk
> 2.5 High Risk


Low or Intermediate 1 risk MDS  are considered to be low risk myelodysplasies, intermediate 2 and high risk MDS, are considered at high risk.




With the term IPSS-r, we mean a prognostic score system introduced in 2011 and updated respect to the IPSS score system. It gives great importance to cytogenetic abnormalities and cytopenias severity and reviews the prognostic weight given to the percentage of blasts. Currently, the most commonly used evaluation system is IPSS, but the IPSS-r is slowly emerging.


Very Good -Y, del(11q)
Good Normal, del(5q), del(12p), del(20q), double incl. del(5q)
Intermediate del(7q), +8, +19, i(17q), any other single or double independent clones
Poor -7, inv(3)/t(3q), del3q, double including -7/del(7q), Complex: 3 abnormalities
Very Poor Complex: > 3 abnormalities


IPSS-R Prognostic Score Values


Prognostic Variable 0 0.5 1.0 1.5 2 3 4
Cytogenetics Very Good Good Intermediate Poor Very Poor
Bone Marrow Blasts (%) ≤ 2 >2 – < 5 5-10 > 10 _
Hemoglobin ≥ 10 _ 8- <10 <8 _ _ _
Platelets ≥ 100 50- < 100 < 50 _ _ _ _
ANC ≥ 8 < 8 _ _ _ _ _



≤ 1.5 Very low
> 1.5 – 3 Low
> 3- 4.5 Intermediate
>4.5 – 6 High
> 6 Very High