Pevonedistat for Myelodysplastic Syndromes

The exact cause of low-risk myelodysplastic syndromes is not resolved. It remains an 'unexplained' disease, and even in the absence of progress in clinical or cytogenetic research, continues to be of importance to the clinician and to its patients and families.

A detailed history is usually the first step in determining the exact diagnosis of the MDS. It is important to note that patients with MDS may have nonspecific symptoms or illnesses such as fevers, night sweats, nausea, or loss of appetite. Clinical trials at Cancer.gov include studies of investigational agents intended for treatment of MDS. Patients should receive the latest treatment information from their physicians. Patient organizations provide education, support, and volunteer activities from time to time.

The American Cancer Society estimates that MDS in the United States will climb steadily between 2014 and 2022 to 9,400 new diagnoses. This is the first forecast to reflect the impact of changes in risk factor management and changes in surveillance strategies.\n

A cure for myelodysplastic syndromes is not technically achievable. However, one recent study has shown a correlation between the use of low doses of etoposide and a statistically insignificant increase in the OS of patients with de novo myelodysplastic syndromes in the 4D study. The role of long-term studies is awaited before further conclusions may be drawn.

Myelodysplastic syndromes are usually diagnosed because of blood abnormalities found in routine blood counts. Some common signs of myelodysplastic syndromes are an increased white blood cell count, thrombocytopenia and/or an abnormally high platelet count. These signs can signify a low red blood cell volume. Lymphadenopathy can be an indicator of myelodysplastic syndromes in which case a bone marrow biopsy may be done.

Chemotherapy treatment for both low- and high-risk MDS is common, and is usually an effective treatment. Hematopoietic stem cell transplantation is possible for all MDS but may be limited to low-risk patients and may be combined with other treatments.

These studies demonstrated the efficacy of pevonedistat in treating chronic myeloid leukaemia and myelodysplastic syndromes. They also established tolerable and acceptable safety profiles with respect to dose and infusion schedule. These studies establish an opportunity to explore further the therapeutic potential of pevonedistat in the treatment of other myeloproliferative disorders for which agents are presently poorly effective or not available.

In MDS patients, the increased levels of [t(8;21)(p22;q22)] that we have detected indicate that it is involved either in the initial pathogenesis of these disorders or in the evolution of some MDS lines. Results from a recent paper may also offer clues to the molecular mechanisms by which the disease progresses in these patients.

Patients with severe disease, MDS-related complications, new MDS-related symptoms, and marrow failure on the bone marrow aspirate may gain greater outcomes from a clinical trials treatment.

About 5% of the pediatric population in the United States is diagnosed or meets the criteria for MDS over the age of 65, but this number is increasing.

In this cohort, the positive LDLK1 (R-G-L) haplotype displayed a trend for familial aggregation (p = 0.05). In the haplotype-revised multiple model, rs10608616 (P (dominant) = 0.049) and rs10154219 (P (dominant) = 0.037) reached the correction threshold and therefore met the significant Haldane principle. Interestingly, the minor (T) haplotype rs10517303 was negatively associated with disease risk, which suggests that this allele could be a high-risk allele in the Caucasian population.