mds
DESCRIPTION
Myelodysplastic syndromesTRANSCRIPT
Myelodysplasia :from marrow failure
to malignant transformation
Ahmed Elshebiny, MDAhmed Elshebiny, MDUniversity of MenoufyiaUniversity of Menoufyia
Blood is continuously renewed
The Bone Marrow is the blood Factory
May be exposed to damage or failure
Bone Marrow Failure Syndromes
Bone Marrow Failure Syndromes
AA PNH MDS
Acquired Constitutional
Autoimmune Fanconi
DC
Diamond-Blackfan
others
Toxic, Irradiation, Infection
Pure Red Cell Aplasia
Agranulocytosis
Bone Marrow Failure May involve one or more cell lines Lymphocytes are usually spared
Venn Diagram
APLASTIC ANEMIA
MDSPNH
AML
Bone Marrow Failure Syndromes
Hematology lectures
Myelodysplastic syndrome (MDS) It is a term for a heterogeneous collection of
haemopoietic stem cell disorders usually affecting older adults.
There is underlying ineffectiveness of haemopoiesis that results in dysplasia of bone marrow precursors and peripheral cytopenias.
Dysplastic erythroid maturation (dyserythropoiesis)
NormalDyserythropoiesis
Pathology The cardinal features of MDS are
Increased marrow proliferation Failure of stem cells to differentiate And increased marrow apoptosis.
The disease is of clonal origin Chromosomal abnormalities are detectable in 30-
70% of patients. The no. of chromosomal abn. may correlate with the risk of progression to AML.
Epidemiology MDS is primarily a disease of the elderly,
with a median age at diagnosis of between 60-80 years.
The incidence is approximately double that of AML.
The recent increase in MDS incidence may be related to growing awareness, better diagnosis, and an aging population.
Etiology Primary Secondary
MDS (clinical) Moderate anaemia is the most common
clinical problem in MDS patients, but complete myeloid bone marrow failure also occurs leading to death from bleeding or infection.
Approximately half of the patients transform to AML.
MDS (clinical) May be preceded by a few years by an
unexplained macrocytic anemia with no evidence of megaloblastic anemia and a mild thrombocytopenia or neutropenia.
Thrombocytopenia as the presenting symptom may be mistaken for immune thrombocytopenia.
Cytogenetic abnormalities in MDS
FAB classification of MDS In 1982 The FAB group classified MDS according
to Morphology and the % of myeloblasts in the BM and PB.
These included Refractory anaemia (RA) Refractory anaemia with ringed sideroblasts (RARS) Refractory anaemia with excess blast in marrow (RAEB) CMML Refractory anaemia with excess blast in transformation (RAEB-t)
FAB classification of MDS
Newer classifications WHO IPSS
Treatment Stem cell transplant DNA methyl transferase inhibitors
Azacytidine Immunomodulation
Thalidomide and lenalidomide Immunosupression Histone deacetylase inhibitors Chemotherapy
Fate of MDS Transformation to acute leukaemia occurs in
up to 40% of patients. Although progression to frank AML is a
primary concern, 20-40 % or more of patients die of infections and/or haemorrhagic complications.
Sideroblastic anemias Inherited (X-linked) Acquired
Myelodysplasis Myeloproliferative disorders Myeloid leukemia Lead toxcicity Drugs e.g INH Alcohol others
Ring sideroblasts
Aplastic Anemias
Aplastic Anemias
Acquired Conistituitional
Single line
Agranulocytosis
Pure Red Cell Aplasia
Multilineage
Aplastic Anemia Named so in 1904 The theoretical basis for marrow failure
includes primary defects in or damage to the stem cell or the marrow microenvironment
Distinction between congenital or acquired may be difficult
80 % of patients have acquired cause which is an autoimmune disease
Aplastic Anemia
Drugs associated with AA NSAIDs(Butazones, Indomethacin,Piroxicam,
Diclofenac) Antibiotics( e.g sulfonamides) Furosemide Phenothiazines Corticosteroids Penicillamine Gold Allopurinol
Pancytopenia
Pancytopenia has many causes of which AA is not the most
common
1-Pancytopenia with hypocellular bone marrow
1. Acquired Aplastic Anemia
2. Inherited Aplastic Anemia
3. Some MDS
4. Rare aleukemic leukemia
5. Some acute lymphoblastic leukemia
6. Some lymphomas of bone marrow
2-Pancytopenia with cellular bone marrow
Primary bone marrow disease1. MDS2. PNH3. Myelofibrosis4. Mylophthisis5. Hairy cell leukemia6. Aleukemic leukemia
Secondary to systemic disease1. SLE2. alcoholism3. B12 or folate difficiency4. Hypersplenism5. Overwhelming infection6. Brucellosis7. Sarcoidosis8. T.B.
3 -Hypocellular marrow with or without cytopenia
1. Q fever
2. Ligionaires
3. Toxoplasmosis
4. Anorexia Nervosa
5. T.B.
6. Hypothyroidism
Investigations of MDS CBC, film, retics….. Bone marrow examination Cytogenitics
Iron Studies SI TIBC Transferrin Saturation Ferritin
Bone marrow aspiration and biopsy
PNH Hemolysis Venous thrombosis Aplastic anemia
P.N.H
PNH and Aplastic Anemia PNH is caused by an acquired genetic defect limited
to the stem-cell compartment affecting the PIGA gene.
Mutations in the PIGA gene render cells of hematopoietic origin sensitive to increased complement lysis.
Approximately 20% of patients with aplastic anemia have evidence of PNH at presentation, as detected by means of flow cytometry.
Furthermore, patients whose disease responds after immunosuppressive therapy frequently recover with clonal hematopiesis and PNH.
Approaches to treatment of Bone Marrow Failure Syndromes
1. Transfusions
2. Growth Factors
3. Immunosuppression
4. SCT
5. Others drugs
References Bethesda Handbook of Clinical hematology
2010 Hamilton et al : Hematology in Clinical
practice 2005 E-medicine online textbook, Hematology Other web resources