MDS comprises a diverse group of clinically and histologically similar disorders, which can be distinguished chiefly on clinical, cytogenetic, and biochemical features. The clinical definition, which includes a peripheral blood monocytosis of less than 1200/microl, remains useful in some respects but is likely to reflect an advanced disease (with high prevalence of SRS).
Around 45,000 people will be diagnosed with MDS/PDS every year in the USA, making these the most common form of blood cancers, the second-most common type of blood cancer overall after non-Hodgkin's lymphoma, and the biggest cause of life-threatening leukemia in females. More than half of MDS/PDS cases occurring in the USA are related to MCP1 fusion gene, FLT3, or mutations of FLT3. Around 30% of MDS and MDS-DS are linked to JAK2, KIT, or TP53 mutations. Around 60% of MDS/MDS-PDS are the result of JAK2 V617F translocations.
As MDS continues to be recognized as a serious disease, a better understanding of its origin and biological mechanisms of action is necessary in order to provide innovative treatments to this patient population.
This guideline has been developed to guide the use of MDS diagnostic criteria for the appropriate diagnosis. The recommendation about the use of the WHO criteria is not applicable in all types of MDS. A diagnosis should only apply to patients who have the requisite clinical/laboratory criteria, as is confirmed by at least two of the following four sets of criteria: WHO or EU/EEU/CFDG criteria for MDS, CMLD criteria or WHO criteria for acute leukemia, and a peripheral blast count greater than 20% of nuclei with a clone. The authors conclude by advising to follow the International Working Group criteria (2016).
Treatment with a bone marrow-stimulating agent such as thalidomide, lenalidomide or bortezomib, can prolong survival and improve quality of life in patients with relapsed/refractory myelodysplastic syndromes.
In MDS, the majority of treatment regimes use anthracyclines and lenalidomide. For elderly patients, consolidation (proton-beam radiation and azacitidine) may be necessary. For younger patients, the decision to use consolidation depends on the number of chromosomal abnormalities, patient age, and response after one course of therapy.
In a recent study, findings indicate that venetoclax is well tolerated in most patients with MDS, particularly as given as monotherapy. Because it represents an exciting new treatment option in older patients with MDS, further studies are warranted.
It was concluded that the risks of developing MS depended on how long the disease was in progress and if any previous procedures were performed. It was also noted that those with high counts of white blood cell blasts have a higher risk of developing MS.
Current research seems to identify the pathophysiology of these disorders but still has significant gaps in its understanding. The disease may not be a consequence of bone marrow dysfunction. Current research supports the use of erythropoietin in patients with myelodysplastic syndromes as well as the use of cladribine as a treatment. Current research also supports the identification of the mutations that cause these diseases.
Age of onset is very variable among different types. The average age at diagnosis when in myelodysplastic syndromes is 64 years old, with an estimated 1-2 years average interval between onset and diagnosis. Therefore, age is an important aspect to look at when considering the diagnosis.
Venetoclax, given as maintenance or in a phase 3 trial, appears to be well tolerated in people with myelodysplastic syndrome and refractory AML. Future studies will need to confirm whether these data extend to people with MDS and chronic myelomonocytic leukemia as a full-blown phase 3 trial in this indication may be warranted. Additional larger dose phase 3 studies with long-term follow-up are still needed to confirm safety.
These data suggest overall improvement in HRQOL through venetoclax across different domains of HRQOL in participants with MDS. More specifically, venetoclax led to improvement in physical functioning, including a decrease in fatigue and improvement in energy, fatigue, and general HRQOL.