The MDS Beacon™

The development of chromosomal abnormalities after diagnosis may have a negative impact on prognosis for myelodysplastic syndromes (MDS) patients according to a recent study published in the Annals of Hematology. 

Italian researchers found that patients who developed misshapen chromosomes after diagnosis in a process called cytogenetic evolution had a 7 times higher risk of shorter survival and a 36 times higher risk of progressing to acute myeloid leukemia (AML) than chromosomally stable patients.

The study revealed that 30.7 percent of MDS patients undergo cytogenetic evolution and that this process is more prevalent in patients with advanced MDS than patients with early or low-risk MDS. These results were independent of pre-existing chromosomal abnormalities discovered at diagnosis. 

The study provided more scientific evidence that MDS progression is accompanied by a steady decrease in genetic stability.

Previous to this study, specific genetic developments had not been clinically and biologically linked with the progression of MDS. 

The researchers analyzed chromosomal profiles of 153 MDS patients at diagnosis, and followed them for a median of 45.2 months. Eighty-four percent of patients were receiving red blood cell transfusions or growth factors, while the remaining 16 percent received immunosuppressive therapy, chemotherapy, or blood cell development-inducing treatments. 

At the end of follow-up, 42.4 percent of patients had experienced worsening of disease after a median 65.2-month period of progression-free survival. A total of 30.7 percent of patients acquired chromosomal defects during follow-up. Twenty-six percent of the patients developed chromosomal abnormalities before their MDS progressed toward more advanced stages or AML. 

Analysis showed MDS patients who did not undergo cytogenetic evolution had significantly longer two- and five-year survival rates (93 percent and 70 percent) compared to patients who developed chromosomal abnormalities (40 percent and 10 percent).

Low-risk MDS patients tended to acquire chromosome 5 and 11 irregularities, while patients with advanced MDS developed abnormalities on chromosomes 7 and 17.  Trisomy 8 occurred equally for low and high-risk patients. The chromosomal abnormality del(7)(q31q34) was the defect that significantly affected the risk of progressing to advanced MDS or AML. 

Researchers concluded MDS patients who developed chromosomal abnormalities during follow-up had an increased risk of shorter survival and progressing to AML by 7 and 36 times, respectively.

For more information, please see the study in the Annals of Hematology (abstract).