Low-dose decitabine increases peripheral NKT-like cell proportions in patients with chronic myeloid neoplasms

Decitabine is widely used in the treatment of chronic myeloid neoplasms, potentially through its immunomodulatory effects on CD8 + T cells and natural killer (NK) cells.. However, as decitabine is often administered in combination with other agents and at varying dosages, the specific effects of low-dose decitabine alone remain unclear. This study aimed to investigate whether low-dose decitabine alone influences immune cell populations. Twelve patients with chronic myeloid neoplasms - including eight with myelodysplastic syndrome, three with myelofibrosis, and one with chronic myelomonocytic leukemia (CMML) - received intravenous decitabine at 5 mg/m 2 for seven days per 28-day treatment cycle. Peripheral blood samples were collected before and after decitabine treatment to assess immune cell proportions and their potential correlation with clinical response. No significant differences were observed in natural killer cells, T cells, CD8 + T cells, CD4 + T cells, or regulatory T cells (Tregs) following decitabine treatment. However, the proportion of NKT-like cells significantly increased from 3.5% to 4.25% ( P = 0.035). Among the three patients who received at least three cycles of decitabine, improvements in anemia and thrombocytopenia were observed in those with elevated NKT-like cell levels. These findings suggest that low-dose decitabine may enhance the NKT-like cell population, potentially contributing to its therapeutic effects in chronic myeloid neoplasms. • Low-dose decitabine (5 mg/m 2 ) alone was administered for seven days in each 28-day treatment cycle to treat chronic myeloid neoplasms. • Decitabine significantly increased the proportion of natural killer T (NKT)-like cells, but not that of NK cells and T cells. • Among the three patients who received at least three cycles of decitabine, improvements in anemia and thrombocytopenia were observed in those with elevated NKT-like cell levels.