Decitabine and Its Therapeutic Potential in MDS

Whether decitabine can completely cure MDS depends on the actual situation. Decitabine is only suitable for MDS with methylated gene abnormalities. If there are four or more gene mutations present simultaneously, the efficacy is poor.

Possible but Uncertain Therapeutic Effects of Decitabine

1. Long-term efficacy of MDS after decitabine demethylation treatment.
2. Preventing MDS from transforming into acute myeloid leukemia, which has not been practically verified.
3. Suitability for treating relapsed and refractory acute leukemia, which is uncertain.

Based on the verification and follow-up results of the above three questions, frankly speaking, decitabine can only be used for MDS with methylated gene abnormalities. Methylated gene mutations are the most common type of gene mutation in MDS. If there are four or more gene mutations present simultaneously, the efficacy of demethylation treatment drugs is poor.

Secondly, demethylation drugs cannot eliminate MDS stem cells, as MDS patients with complete hematological remission still have different loads of gene mutations. Therefore, in clinical practice, the treatment of MDS lacks effective and standardized therapeutic drugs. Demethylation treatment has been overstated in current MDS treatment, with widespread issues such as excessive drug dosages, excessive treatment durations, exaggerated efficacy claims, and exaggerated expectations.

Reasons for the Potential Ineffectiveness of Decitabine

The main reason for the potential ineffectiveness of decitabine lies in the lack of therapeutic drugs for MDS, and both doctors and patients place too much hope on the demethylation treatment effect of decitabine. When methylated gene abnormalities and mutations are found in MDS diagnosis (referring only to the second category of MDS-affected genes), decitabine-like demethylation treatment can be considered. Nevertheless, it should be noted that demethylation drugs have a certain degree or severe inhibitory effect on the bone marrow and cannot solve all problems associated with MDS. Therefore, cautious analysis and weighing are required in the following situations:

1. The percentage of blasts in the bone marrow does not exceed 5%.
2. No demethylation-related genes are detected.
3. There is a certain or significant tendency for bone marrow fibrosis (increased reticular fibers in the bone marrow).
4. Significant reduction in all blood cells.
5. Poor drug tolerance.

Clinical observations have shown that even when the percentage of blasts in the bone marrow increases to over 5% or 10%, demethylation treatment still cannot prevent further disease progression and transformation. Temporary reductions in blasts may eventually rebound, especially in states of further decreased or failed bone marrow hematopoiesis.