High pretreatment levels of fetal hemoglobin (HbF) in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia may predict better outcomes with azacitidine treatment, according to a study published in Internal Medicine.

This single-center, retrospective study included 21 patients with MDS, 5 patients with chronic myelomonocytic leukemia, 2 patients with acute myeloid leukemia with less than 30% marrow blasts, and 1 patient with an unclassifiable myelodysplastic/myeloproliferative neoplasm.

According to the revised International Prognostic Scoring System classification, 20 of 29 patients were at intermediate, high, or very high risk. The participants, who had never received chemotherapy before, were treated with azacitidine for 7 days.

To evaluate HbF as a potential prognostic marker for patients treated with azacitidine, the researchers measured HbF levels at the onset of treatment, between March 2011 and July 2020, and followed up the participants for a median of 13 months.

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Based on these values, the patients were divided into HbF-normal (<1.0%) and HbF-elevated (≥1.0%) groups. Of 29 patients, 13 belonged to the HbF-elevated group.

The results noted that the hematologic improvement rate was significantly higher in the HbF-elevated group compared with the HbF-normal group (76.9% vs 25%), as well as the overall survival rate (median 21 vs 13 months).

“As a possible mechanism, we speculate that genetic abnormalities involved in HbF elevation and those involved in azacitidine responsiveness may correlate in the HbF-elevated group,” Saga and colleagues noted.

“HbF levels, which can be easily measured in the peripheral blood, are a useful parameter in daily clinical practice. Further prospective studies involving genetic analyses with a larger sample size are needed.”

Azacitidine remains the standard of care for high-risk older patients with MDS. Although the prognostic value of HbF has been established for decitabine therapy, there is limited evidence on HbF level significance for azacitidine monotherapy and reliable clinical outcome predictors are yet to be identified.


Saga T, Kanagawa M, Harada T, Lang L, Yamawaki F, Ishihara T. Prognostic value of pretreatment fetal hemoglobin levels in patients with myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine: a single-center retrospective study. Intern Med. Published online July 26, 2023. doi:10.2169/internalmedicine.1216-22