MLAB 1415- Hematology

Keri Brophy-Martinez

Chapter 23: Myelodysplastic Syndromes

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

Terms used to describe MDS

Preleukemic leukemia or syndrome Preleukemic acute human leukemia Chronic refractory anemia with

sideroblasts Smoldering leukemia

Risk factors Age Genetic predisposition

• Chromosomes 5,7 and 8

• Down’s, Fanconi’s Environmental exposures

• benzene Prior therapy

• Radiation

• Chemotherapy

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.

Hematologic abnormalities in MDS

Findings Erythroid Myeloid Thrombocyte

Peripheral blood AnemiaMacro, oval macro,basophilic stippling, nRBC, Howell-Jolly bodies,sideroblastsaniso, 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

•Micromegakaryocytes•Megakaryocytes with multiple nuclei•Hypogranulation

Dysgranulopoiesis

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)

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

MDS/MPD 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

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)

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.

References

McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 21." Introduction. Clinical Laboratory Hematology. Boston: Pearson, 2010. Print