From the Guidelines
Myelodysplastic syndrome (MDS) can progress to acute myeloid leukemia (AML), with key signs of conversion including a rapid increase in blast cells, worsening cytopenias, and new or worsening symptoms. The most recent and highest quality study, 1, provides guidance on the classification and diagnosis of MDS, including the signs of conversion to AML.
Key Signs of Conversion
- A rapid increase in blast cells in the bone marrow or blood (reaching or exceeding 20%, which defines AML)
- Worsening cytopenias (particularly decreasing blood counts despite treatment)
- Increased transfusion dependence
- New or worsening symptoms such as fatigue, infections, bleeding, bone pain, and fever
- Enlargement of the spleen or liver
- Laboratory tests showing increasing lactate dehydrogenase (LDH) levels ### Patient Subgroups The study 1 highlights the importance of considering patient subgroups, such as those with higher-risk MDS, particularly those with certain genetic abnormalities like complex karyotypes or mutations in genes such as TP53, RUNX1, or ASXL1.
Monitoring and Treatment
Regular monitoring through complete blood counts and bone marrow examinations is essential for early detection of transformation, as noted in 1.
Progression Rate
The progression rate varies widely among patients, with higher-risk MDS subtypes having a 25-30% annual risk of progression to AML, while lower-risk subtypes have a much lower risk of around 5-10% annually, as reported in 1. Early recognition of these signs allows for timely intervention with appropriate AML treatment protocols.
From the FDA Drug Label
The study endpoints were overall response rate (complete response + partial response) and time to AML or death Decitabine for injection treatment did not significantly delay the median time to AML or death versus supportive care. The FDA drug label does not answer the question.
From the Research
Signs of MDS Converting to Acute Leukemia
- Increased risk of transformation to acute myelogenous leukemia (AML) is a characteristic of myelodysplastic syndromes (MDS) 2, 3
- Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy, with additional studies such as karyotype, flow cytometry, and molecular genetics providing complementary information 2, 3
- Prognosis of patients with MDS can be calculated using scoring systems, including the International Prognostic Scoring System (IPSS) and the Revised International Prognostic Scoring System (IPSS-R), which take into account factors such as peripheral cytopenias, percentage of blasts in the bone marrow, and cytogenetic characteristics 2, 3
- Somatic mutations can also help define prognosis and therapy in MDS patients 2, 3
Risk Factors for Conversion to AML
- Higher-risk MDS patients are more likely to experience transformation to AML 4
- Parameters influencing the probability of achieving complete remission (CR) after intensive chemotherapy include blast count in the bone marrow, age, presence of Auer rods, duration of antecedent MDS, and timing of intensive chemotherapy 4
- Achieving CR, presence of Auer rods, and percentage of blasts below 30% are significant factors influencing median survival in MDS patients 4
Treatment Options for MDS and AML
- Current available therapies for MDS include growth factor support, lenalidomide, hypomethylating agents (such as 5-azacitidine and decitabine), intensive chemotherapy, and allogeneic stem cell transplantation 2, 3, 5, 6
- Hypomethylating agents, such as azacitidine and decitabine, have been shown to improve outcomes in patients with AML and higher-risk MDS, with decitabine demonstrating higher efficacy in terms of complete remission rate 6
- Intensive chemotherapy is not a promising treatment option for high-risk MDS or secondary AML, due to high relapse rates and short survival times 4