Some patients with myelodysplasia classified as lower risk by the International Prognostic Scoring System (IPSS) may show rapid progression, Mittelman et al identified factors associated with a poor prognosis. The authors are from Tel Aviv University.
Patient selection: low risk or intermediate-1 MDS
Outcome: poor prognosis
General findings associated with worse survival:
(1) older age
(2) male gender
(3) significant comorbidities
(4) poor performance status
Cytopenias and blood transfusion:
(1) anemia
(2) thrombocytopenia
(3) absolute neutropenia
(4) need for repeated transfusion
(5) elevated serum ferritin and iron overload
Laboratory values:
(1) elevated serum LDH concentration
Bone marrow findings:
(1) fibrosis
(2) blast islands (clusters of CD34 positive cells)
(3) multi-lineage dysplasia
(4) normal or high cellularity (versus hypoplasia)
Immunophenotyping:
(1) increased CD34 (blast marker)
(2) increased CD13
(3) increased CD45
(4) increased HLA-Dr
(5) low CD11b
(6) increased BCL2
Cytogenetics:
(1) additional chromosomal abnormalities (versus low risk pattern)
(2) chromosomal instability
Genetic testing:
(1) 6-gene poor risk signature
(2) unmutated TET2
(3) mutation ASXL1
Other (may not be readily available):
(1) short telomeres
(2) high telomerase activity
(3) cell senescence (PIG INKa4)
(4) P15 INK4b methylation
(5) CTNNAI
(6) high methylation
(7) down regulation LEF1
(8) increased caspase3
(9) clonal granulocytes
Observations:
• Some of the measures in the IPSS are subject to inter-observer variability.
• Patients classified as intermediate-1 MDS would seem more likely to progress.
• MDS evolves over time and so requires periodic evaluation, especially when diagnosed early in its course.
