University of Virginia Health System

Myelodysplastic Syndrome (MDS)

Description:

These disorders are a diverse group, and are the result of a clonal proliferation of hematopoietic cells that may be of one or more lineages. Unlike most of the myeloproliferative disorders, the hallmark findings are dysplasia of the lineages involved and ineffective hematopoiesis. In the setting of cytopenias which may involve one lineage (e.g. anemia) or multiple lineages (e.g. pancytopenia), the bone marrow is usually normocellular or hypercellular in contrast to aplastic anemia where the bone marrow is very hypocellular. And in contrast to the myeloproliferative disorders where the bone marrow also is hypercellular, there is dysplasia of the cellular lineages involved.

The single often significant diagnostic presentation is cytoplasmic hypogranularity of the neutrophils with Dohle bodies. Hypolobation of the neutrophil nuclei, some assuming a "dumbbell shape" is also an important finding, but in the absence of hypogranularity, must be distinguished from normal late metamyelocytes and early bands, and from the rare congenital entity, Pelger-Huet disorder. An increase in nuclear sticks on the more mature neutrophils is less specific, and must be moderate to severe to have significance. An elevated MCV with a dimorphic red cell picture (presence of macrocytes and microcytes), is a frequent finding, but is nonspecific, as is a variable degree of anisopoikilocytosis. Megaloblastic changes in the nucleated red blood cells (NRBCs) also is nonspecific, but take on more significance in the absence of other known causes (e.g. vitamin B12 and folate deficiency, certain drugs). Bilobed and multilobed NRBCs along with an increase in karyorrhexis are also features. Hypolobation of the megakaryocytes characterizes the 5q- subtype.

Several classifications of these disorders have been proposed, but none encompass the entire spectrum of the varied clinopathologic findings. From a prognostic standpoint several finding portend a poor prognosis.

• Poor prognostic factors include:
  • Increased numbers of blasts in the peripheral blood and bone marrow
  • Multilineage dysplasia
  • Certain cytogenetic abnormalities (e.g. chromosome 7 abnormalities)
  • Severity of the cytopenias
• Good prognostic factors include:
  • Single lineage involvement, especially if erythroid only, either refractory anemia with ring sideroblasts (SA) or without (RA).
  • The 5q- syndrome

Two classifications have gained widespread use:

French-American-British (FAB) Classification

• Refractory anemia (RA)
• Refractory anemia with ringed sideroblast (SA)
• Refractory anemia with excess blasts (RAEB)
  • 5-20% blasts in bone marrow
• Refractory anemia with excess blasts in transition (RAEB-t)
  • 21-30% blasts in bone marrow
• Transformation to acute leukemia
  • blasts >30% in bone marrow
• Chronic myelomonocytic leukemia (CMML)
  • May have up to 20% blasts in bone marrow

World Health Organization (WHO) Classification

• Refractory anemia (RA)
• Refractory anemia with ringed sideroblasts (RARS)
• Refractory cytopenia with multilineage dysplasia (RCMD)
• Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-s)
• Refractory anemia with excess blasts-1 (RAEB-1): 5-9% blasts in bone marrow
• Refractory anemia with excess blasts-2 (RAEB-2): 10-19% blasts in bone marrow
• Myelodysplasia syndrome- unclassified (MDS-u)
  • Unilineage dysplasia of granulocytic or megakaryocytic lineage
• 5q- syndrome
  • Anemia in setting of a normal or even elevated platelet count, and monolobated megakaryocytes in bone marrow.

General References:

• Bennett JM, Catovsky D, Daniel MT, et al: FAB Cooperative Group: Proposal for the classification of the myelodysplastic syndrome. Br J Haematol 51:189, 1982
• Greenberg P, Cox C, LeBeau MM, et al: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89: 2079, 1997
• Malcovati L, DollaPorta MG, Pascutto C, et al: Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J. Clin Oncol 23; 7594, 2005
• Harris NL, Jaffe ES, Diebold J, et al: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee meeting- Airlie House, Virginia, November 1997. J Clin Oncol 17: 3835, 1999