1. MLAB 1415- Hematology Keri Brophy-Martinez
Chapter 23: Myelodysplastic Syndromes

2. MYELODYSPLASTIC SYNDROMES
A group of acquired clonal hematologic disorders characterized by progressive cytopenias in the peripheral blood, reflecting defects in erythroid, myeloid and/or megakaryocytic maturation.
Bone marrow is hyperplastic
The result in impaired hematopoiesis.
The origin is currently unknown.
Affects people over 50 with a slight male predominance

3. Terms used to describe MDS
Preleukemic leukemia or syndrome
Preleukemic acute human leukemia
Chronic refractory anemia with sideroblasts
Smoldering leukemia

4. Risk factors Age Genetic predisposition Chromosomes 5,7 and 8
Down’s, Fanconi’s
Environmental exposures
benzene
Prior therapy
Radiation
Chemotherapy

5. Clinical findings
Symptoms are related to progressive bone marrow failure
Infections
Bleeding
Weight loss
Cardiovascular
Death usually occurs from infection and/or bleeding or from leukemia if transformation occurs.

6. Hematologic abnormalities in MDS
Findings
Erythroid
Myeloid
Thrombocyte
Peripheral blood
Anemia
Macro, oval macro,basophilic stippling, nRBC, Howell-Jolly bodies,sideroblasts
aniso, poik
Neutropenia
Dysgranulopoiesis:
Agranular or hypogranular neutrophils, Abnormal granulation of neutrophil precursors,
Hyposegmented neutrophils
Thrombocytopenia/thrombocytosis
Hypogranulation
Micromegakaryocytes
Functional abnormalities
Giant platelets
Bone Marrow
Megaloblastic erythroblasts
nuclear fragments
multiple nuclei
vacuoles
Abnormal granules in promyelocytes
Absence of secondary granules
Auer rods in blasts
Megakaryocytes with multiple nuclei

7. Dysgranulopoiesis

8. FAB classification Five MDS subtypes: Refractory anemia (RA)
Refractory anemia with ringed sideroblasts (RARS)
Refractory anemia with excess blasts (RAEB)
Refractory anemia with excess blasts in transformation (RAEB-t)
Chronic myelomonocytic leukemia (CMML)

9. WHO classification Refractory anemia (RA)
Anemia is primary finding, but unresponsive to treatment
Refractory anemia with ringed sideroblasts (RARS)
>15% ringed sideroblasts in bone marrow
Refractory cytopenia with multilineage dysplasia (RCMD)
Dysplastic features in at least 10% of cells in two or more lines
RA with excess blasts-1 (RAEB)
Cytopenia in at least two lineages, with qualitative abnormalities in all three cell lines

10. MDS/MPD Diseases Diseases
Clonal hematopoietic neoplasms that at initial presentation have some clinical, laboratory or morphological findings of both a MDS/MPD
Abnormalities in the regulation of myeloid proliferation, maturation and cell survival
Diseases
CMML associated with persistent monocytosis
Others

11. Chronic Myelomonocytic Leukemia (CMML)
Monocytosis
↑ in mature monocytes (some forms have ↑ monoblasts and promonocytes)
Bone marrow hypercellular
Splenomegaly and hepatomegaly (in patients with high WBC count)

12. Therapy
Currently, there is no really good treatment for MDS, therefore most therapy is supportive, such as transfusion of blood components and antibiotics.
Treatments that modulate the immune system, such as steroids and interferon have been used to some success.
The only effective treatment is bone marrow transplant, but most patients are too old to survive the rigors of this treatment.

13. References
McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 21." Introduction. Clinical Laboratory Hematology. Boston: Pearson, Print