MDS Zentrum Dresden

MDS Zentrum Dresden
Universitätsklinikum Carl Gustav Carus | MDS Center of Excellence
 

  

Clinical Picture

 

Myelodysplastic Syndromes (MDS) constitute an acquired, complex group of conditions within the bone marrow. Thus it is a blood disease as well since blood cells are generated in the marrow. Usually it occures at an older age, mainly from the age of 60. Thereby men are affected slightly more often than women.

MyeloDysplastic Syndrome  =  Marrow Malformation Syndrome

MDS is not heritable and its causes are mostly unknown. Risk factors such as chemotherapy, radiotherapy or toxic substances (e.g. benzene, pesticides, smoking, alcohol) are being discussed, however in most cases a definite cause can not be determined. About 1/3 of all patients develop acute myeloid leukaemia (AML), in turn 2/3 suffer from mutated chromosomes (genetic information carrier) in the diseased cells.

 

  

 

Blood System

 

Our blood's function is transporting oxygen and nutrients / waste substances through the human body. Furthermore it is responsible for the immune defense and the regulation of body fluids. Blood cells are formed in the bone marrow from immature stem cells. Hereinafter the three main types of blood cells are listed.

Red Blood Cells
(Erythrocytes)

Platelets
(Thrombocytes)

White Blood Cells
(Leukocytes)

erythrozyt

Thrombozyt

Leukozyt

  • Oxygen (O2)- /
    Carbon Dioxide (CO2)-
    transport cells
  • Hemoglobin (Hb) attaches O2
  • standard: 12-16 g/dl
  • coagulation cells
  • stop bleeding
  • standard: 150,000 - 300,000 cells/µl
  • part of the immune system
  • Granulocytes (defense of bacteria, parasites, fungus)
  • Monocytes - precursor of Makrophages (scavenger cells) and dendritic cells (antibody presentation)
  • Lymphocytes (B-, T-, and killer cells)

 

  

 

Symptoms

 

In the case of MDS, blood formation is disordered, which means that there are malfunctions during maturation and dysfunctions of the bone marrow cells. In the process too many immature marrow cells are being produced - so called blasts or leukemic cells, displacing healthy blood cells. As a result inter alia the following symptoms occur:

Anemia
(blood poverty)

Thrombocytopenia
(bad blood clotting)

Leukopenia
(infection vulnerability)

  • paleness
  • exhaustion
  • shortness of breath
  • decrease of performance
  • headache / dizziness
  • bruising
  • nosebleed
  • bleeding of gums
  • heavy bleeding after minor injuries
  • often protracted infections
  • fever
  • pneumonia
  • urinary tract infections

 

 

  

 

Diagnostics

 

Altered blood parameters are a first indicator for particular examinations. If no other cause for the symptoms is found, a bone marrow puncture will be necessary for clarification.

Blood Examination

blutabnahme

Bone Marrow Biopsy

kmp

  • blood count:
    composition, proportion of blood cells
  • differential blood:
    composition of leukocytes
  • laboratory:
    Serum Ferritin, LDH, VitB12, folic acid, EPO
  • cytology:
    microscopical analysis of a bone marrow smear
  • cytogenetics:
    examination of the cell chromosomes (genotype)

 

  

 

Classifications

 

The MDS subtype depends on the results of differential blood and cytogenetical tests. A distinction is made between WHO (World Health Organisation)- and FAB (French-American-British)-classification. The IPSS-R-Score (Revised International Prognostic Scoring System) is used for determining the disease severity.

 

  • according to FAB:

FAB subtype

category

blasts in bone marrow

RA

refractory anemia

<5 %

RARS

refractory anemia with ringed sideroblasts

<5 %
15 % ringed sideroblasts

RAEB

refractory anemia with excess of blasts

5-20 %

CMML

chronic myelomonocytary leukemia

<20 %
increased promonocytes

RAEB-T

RAEB in transformation

21-30 %
Auer's bodies

source: Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33(4):451-8.

 

  • according to WHO:

MDS classification according to WHO

 

  

 

Therapy

 

The MDS therapy depends on the MDS subtype, the patient's individual condition, comorbidities, and available treatment options. There are therapies as follows:

  • "wait and see"
  • supporting therapy:

These are treatments not fighting the disease itself, but parts of its symptoms, e.g. by means of blood transfusion, growth hormones and therapies of iron overload.

  • disease-modifying therapy:

If the bone marrow loses functional capabilities, substances are used that can modify the characteristics of MDS. Therefore immunomodulatory and demethylating substances as well as induction chemotherapies are applied.

  • bone marrow / stem cell transplantation:

Diseased bone marrow is substituted with stem cells of a healthy donor to have it rebuilt. This form of therapy is considered the sole chance of healing and - unfortunately - applicable for few patients only. The main reasons for this can be the patient's age being too high as well as his/her improper condition - or a lack of suitable donors.

  • clinical trials:

For the future development of new therapies it is important to supervise treatment options with not yet approved substances - in compliance with strict protocols.

source: http://www.mds-foundation.org

 

  

 

Research

 

Our research is focused on clinical trials with all new substances for the treatment of MDS.

  • the role of immune regulation in MDS
  • the role of iron overload in allogenic stem cell transplantation