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Myelodysplasia syndrome (MDS)

Heri Fadjari

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Intro

MDS are clonal hematologic disorders characterized clinically and

morphologically by ineffective hematopoiesis.

The natural history of these syndromes ranges from a chronic course that

may span years to a rapid course of leukemic progression. Unfortunately,

the nomenclature and classification systems used to describe these

conditions are cumbersome.

In general, myelodysplastic conditions are preleukemic disorders in which

the neoplastic clone is established, but not all cases of myelodysplasia

terminate in acute myeloid leukemia (AML).

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Clinical manifestations

Although patients with MDS may seek medical care because of symptoms of

hematopoietic failure such as infection, bleeding, bruising,

progressive fatigue, or dyspnea on exertion.

Many patients present without symptoms but with anemia, thrombocytopenia,

leukopenia, or a combination of these findings on routine laboratory evaluation.

Generally affects older adults, with a median age at onset in the 7th decade,

although cases in children have been reported.

Men account for a somewhat larger proportion of cases than women (6:4)

The 5q- Syndrome: Mild netropenia, normal to high plts count

Hypoplastic Myelodysplasia: hypoplastic bone marrow

Childhood Myelodysplasia: Downs syndrome

Myelodysplasia with Bone Marrow Fibrosis

Therapy-Related Myelodysplasia: Alkylating agents, anthracyclines

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Morphological manifestations

Megaloblastic

erythropoiesis

with cytoplasmic

blebbing in a

bone marrow

specimen

Multinucleated

erythroid

precursor in a

bone marrow

specimen

Multinucleated

erythropoiesis

in a

bone marrow

specimen

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Morphological manifestations

Pseudo Pelger-

Huet neutrophyl

in

peripheral blood

smear

Micromega-

karyocyte

in a

bone marrow

specimen

Ringed sideroblast

in a

bone marrow

specimen

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FAB classification

Refractory anemia (RA)

Cytopenia of at least one lineage in the peripheral blood (usually anemia)Normal or hypercellular bone marrow with dysplastic changes

Less than 1 percent blasts in the peripheral blood and less than 5 percent

blasts in the bone marrow

Refractory anemia with ringed sideroblasts (RARS)

Cytopenia (almost always anemia), dysplastic changes, and the same percentages

of blood and bone marrow blasts as in refractory anemiaRinged sideroblasts accounting for more than 15 percent of all nucleated

cells in the bone marrow

Refractory anemia with excess blasts (RAEB)

Cytopenia of two or more lineages in the peripheral blood

Dysplastic changes in all three lineagesLess than 5 percent blasts in the peripheral blood and between 5 and 20

percent blasts in the bone marrow

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FAB classification

Chronic myelomonocytic leukemia (CMMoL)

Peripheral-blood monocytosis (monocyte count, >1000/mm3)Less than 5 percent blasts in the peripheral blood and up to 20 percent

blasts in the bone marrow

Refractory anemia with excess blasts in transformation (RAEBt)

Hematologic features similar to those of refractory anemia with excess

blasts

More than 5 percent blasts in the peripheral blood or between 21 and 30percent blasts in the bone marrow or the presence of Auer rods in the

blasts

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FAB vs WHO classification

RA Refractory anemia (RA)

Refractory cytopenia with multilineage dysplasia (RCMD)

Myelodysplastc syndrome, unclassified (MDS-U)

MDS with isolated del(5q)

RARS Refractory anemia with ringed sideroblasts (RARS)

Refractory cytopenia with multilineage dysplasia

and ringed sideroblasts (RCMD-RS)RAEB Refractory anemia with excess blasts-1 (RAEB-1)

Refractory anemia with excess blasts-2 (RAEB-2)

RAEB-t Now classified as AML

CMMoL Now classified with myeloproliferative diseases)

FAB WHO

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IPSS for MDS

OVERALL SCORE MEDIAN SURVIVAL

Low 0 5.7 yrs

Intermediate

1 (0.5 or 1.0) 3.5 yrs

2 (1.5 or 2.0) 1.2 yrs

High >2.5 0.4 yrs

IPSS=International Prognostic Scoring System

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IPSS for MDS

The percentage of blasts is scored as follows:

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Treatment options

In general, the results of such treatments have been disappointing; patients with

preexisting myelodysplasia tend to have a lower rate of complete remission, a shorter

duration of remission, and a higher rate of relapse thanpatients with newly diagnosed acute leukemia.

Patients with myelodysplasia who receive standard induction regimens for AML that

include an anthracycline and cytarabine have a remission rate of 50-60% with relapse

rate of 90%, whereas patients with newly diagnosed AML who are treated with similar

regimens have a remission

rate of 70-80% with relapse rate of 65-80%.

MDS with karyotype 7q-, 8+ also associated with a poor prognosis

Treatment of myelodysplasia should be tailored to the biology of the disease. Given the

unsatisfactory response to standard treatment regimens, MDS patients might be

considered for high-dose chemotherapy and stem-cell transplantation.

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Treatment options

Immunotherapy

Several lines of evidence suggest that modulation of the immune response might be

useful in the treatment of myelodysplastic conditions.Antithymocyte globulin,antibody against CD33 may soon play a part in the treatment of myelodysplasia.

Hematopoietic Hormones and Cytokines

Both granulocyte colony stimulating factor (G-CSF) and granulocytemacrophage

colony-stimulating factor (GM-CSF) increase the level of circulating neutrophils in 80

to 90 percent of patients and may decrease the risk of infection.

Treatment with erythropoietin (epoetin) increases the hematocrit in approximately 25percent of treated patients, leading to decreased transfusion requirements.

Stem-Cell Transplantation

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Questions?