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Myelodysplastic Syndromes

  • MDS – decreased number of morphologically abnormal cells that often don’t function properly
  • Clonal proliferations of hematopoietic stem cells
  • Many cells die in the BM – ineffective hematopoiesis
    • Therefore MDS are characterised by cytopenias, abnormal morphology, impaired function of cells
  • Majority of pts die of BM failure
  • Aggressive forms of MDS resemble AML (distinction can be difficult)

Classification

  • FAB – based on number of myeloblasts in blood and BM
    • But has limited prognostic ability
  • Modifications in the WHO classification
    • RA and RARS are limited to cases with dysplastic changes restricted to erythroid series only (patients have a longer survival)
    • RCMD – <5% myeloblasts in BM but with dysplastic changes in two or more cell lines (pts have shorter survival)
    • RAEB – is divided into RAEB-1 and RAEB-2 depending on myeloblast count and presence/absence of Auer rods
    • RAEB-t – is eliminated in the WHO system
      • Cases that fit in this category in FAB are now classified as AML
    • Myelodysplasia arising in patients who previously received chemo for a malignant disease is now classified as AML
    • Patients with characteristic AML translocations [t(8;21), t(15;17) or inversion (16)] are classified as AML even if blast count is low
    • CMML is moved to a new disease category – the ‘myelodysplastic/myeloproliferative syndromes’

Epidemiology

  • MC in older men
  • Etiology mostly unknown
  • ↑risk with exposure to ionizing radiation, chemotherapy, benzene

Clinical features

  • 50% detected as incidental findings
  • Clinical variants
  • Symptoms are related to cytopenias – fatigue due to anaemia is MC
  • History of multiple infections
  • Patients may have petechiae, purpura, mild splenomegaly
    • Marked splenomegaly is more indicative of a myeloproliferative disorder than MDS

Diagnosis

  • Most patients are anemic
  • Normal/high MCV
  • Leukopenia, thrombocytopenia, pancytopenia
  • Blood smear
    • Anisocytosis of er
    • Neutrophils have abnormal segmentation and are hypogranular
      • Pseudo Pelger-Huet anomaly
      • Decreased MPO activity
  • Bone marrow
    • Hypercellular
    • Er precursors are enlarged
    • Er nuclei appear karyorrhexic – nuclear fragmentation
    • Granulocytes have nuclear-cytoplasmic asynchrony
    • Increased myeloblasts
    • May be presence of ringed sideroblasts
      • Nucleated erythroid precursors with granules adjacent to the nucleus (on Prussian blue stain)
    • Cells in abnormal locations
      • E.g. er precursors located next to bone trabecula (they are normally located away from bone)

Cytogenetics

  • Crucial in prognosis
  • Partial/complete chromosome deletions
    • MC in chromosomes 5,7,8,20

Disease course

  • Highly variable
  • RA + RARS – low grade, prolonged survival, low rate of transformation to AML
  • RAEB and RAEB-t – high grade
  • RCMD – intermediate
  • MCC of death – infection, hemorrhage, leukemic transformation
  • Most important prognostic factors – age; % myeloblasts in BM; no. of cell lines with cytopenia; cytogenetics
  • International Prognostic Scoring System (IPSS)

Treatment

  • Older patients with comorbidities unable to tolerate aggressive therapies
  • Control of symptoms is primary goal
  • Supportive – transfusions, antibiotics for infection
  • Pyridoxine – for pts with RARS only
  • Hematopoietic growth factors (erythropoietin, G-CSF, GM-CSF (pegfilgastrim)
  • Chemotherapy – low response rates compared to pts with de novo AML
    • Cyclosporin, Azacitabine, Lenolidamide (5q syndrome)
  • BMT – only curative. Pts with RA + RARS have best response
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