Effect of Treatment with Azacitidine on CD4+CD25+Foxp3+ Regulatory T Cells in Myelodysplastic Syndrome Survivors

• Published in: Blood 2016-12, Vol.128 (22), p.4325-4325
• Main Authors: Tajima, Fumihito, Adachi, Koji, Kawatani, Toshio
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.4325.4325

Background: Regulatory T cells (Treg) play an important role in immune surveillance of malignancies. Treg expansion occurs frequently in high-risk myelodysplastic syndrome (MDS) and in progression of this disease. Azacitidine (AZA) is increasingly used for treatment of MDS. In this study, we examined changes in the number of circulating Treg in peripheral blood of patients with MDS treated by AZA and we evaluated the clinical significance of these changes. Patients and Methods: Patients with MDS and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) according to the WHO 2008 classification who were initially treated between January 2015 and December 2015 and followed up for more than six months were enrolled in the study. AZA was given intravenously at a dose of 75 mg/m2 daily for 5 or 7 consecutive days every 4 weeks. The response was assessed using the IWG response criteria for MDS. A total of 29 patients with AML-MRC (n=5), refractory anemia with excess blasts (RAEB) (n=7), refractory cytopenia with multilineage dysplasia (RCMD) (n=16), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) (n=1) were included in the study. IPSS was intermediate-1 (n=15), intermediate-2 (n=6), and high (n=8). Eighteen patients did not need treatment, including transfusion (untreated group). Eleven patients were treated with AZA (AZA group). After obtaining informed consent, blood was drawn from all patients at initial diagnosis. In the 11 patients treated with AZA, blood was also drawn after 6 completed cycles. CD4+CD25+Foxp3+ Treg cells, CD3+CD8+ T cells, and CD3-CD56+ NK cells were analyzed using flow cytometry and the absolute numbers of these cells were calculated. Results: The median age was 74 years (range: 44-88) and 22 of the patients were male. The median period of observation was 283 days. In the AZA group, 3 patients died and one had recurrence (AZA-ineffective group), and 7 reached CR or PR (AZA-effective group). The absolute number of Treg was higher in AML/MRC + MDS/MPN than in RCMD (32.5 ± 19.6 vs. 16.4 ± 11.9 /μL, p=0.0234). Treg% values in peripheral blood before treatment in the AZA (1.17±0.80%), AZA-effective (1.15±0.54%), and AZA-ineffective (1.21±1.24%) groups were all significantly higher than that in the untreated group (0.49±0.26%, p=0.0022, p=0.0004, p=0.0241, respectively). Similarly, the absolute numbers of Treg were significantly higher in the AZA (31.9±17.0 /μL), AZA-effective (24.3±11.5 /μL), and AZA-ineffective (45.1±