» Articles » PMID: 29922595

Immunemodulatory Effects of 5-Azacitidin Through Expansion of Functional Regulatory T Cells on Paraneoplastic Inflammation Associated With Myelodysplastic Syndromes: A Case Report

Overview
Journal Front Oncol
Specialty Oncology
Date 2018 Jun 21
PMID 29922595
Authors
Affiliations
Soon will be listed here.
Abstract

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic stem cells, characterized by dysplastic hematopoiesis and dysregulated immune system resulting in various clinical conditions. Paraneoplastic inflammatory syndromes, which are well known to be associated with MDS, show response to immune-modulated therapy and often disappear during the course of hematologic management. Azacitidine (5-Aza) was shown to prolong survival of high-risk MDS patients, however, the effects of 5-Aza on paraneoplastic inflammation in MDS have yet to be elucidated. 5-Aza was administered to a 60-year-old man with MDS accompanying Sweet's syndrome at a dose of 75 mg/m/daily subcutaneously for 7 days every 28 days. 5-Aza was not only effective in controlling systemic symptoms caused by paraneoplastic inflammation, but hematologic improvements were also observed after four cycles of the 5-Aza treatment. Immune profiling in peripheral blood before and after 5-Aza treatment revealed that the effector and naive regulatory T cells in lymphocytes drastically increased after the 5-Aza treatment, i.e., 5-Aza might induce a shift in lymphocytic populations toward immunosuppression in this patient. Our results raised the immune-mediated effect of 5-Aza on both dysplastic hematopoiesis and paraneoplastic inflammation in myelodyplastic syndromes.

References
1.
Pilorge S, Doleris L, Dreyfus F, Park S . The autoimmune manifestations associated with myelodysplastic syndrome respond to 5-azacytidine: a report on three cases. Br J Haematol. 2011; 153(5):664-5. DOI: 10.1111/j.1365-2141.2010.08557.x. View

2.
Enright H, JACOB H, Vercellotti G, Howe R, Belzer M, Miller W . Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes: response to immunosuppressive therapy. Br J Haematol. 1995; 91(2):403-8. DOI: 10.1111/j.1365-2141.1995.tb05310.x. View

3.
Aggarwal S, van de Loosdrecht A, Alhan C, Ossenkoppele G, Westers T, Bontkes H . Role of immune responses in the pathogenesis of low-risk MDS and high-risk MDS: implications for immunotherapy. Br J Haematol. 2011; 153(5):568-81. DOI: 10.1111/j.1365-2141.2011.08683.x. View

4.
Fraison J, Mekinian A, Grignano E, Kahn J, Arlet J, Decaux O . Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res. 2016; 43:13-7. DOI: 10.1016/j.leukres.2016.02.005. View

5.
Fenaux P, Mufti G, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A . Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009; 10(3):223-32. PMC: 4086808. DOI: 10.1016/S1470-2045(09)70003-8. View