Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes

Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin

“…10,12,24,25 ATG has been used successfully in the alleviation of cytopenias in severe aplastic anemia, 25 and while earlier reports from Molldrem et al and Killick et al had identified BM hypocellularity as an important factor predicting with ATG response, several recent reports have failed to confirm this association. [14][15][16]22 Our study indicates that patients with hypocellular MDS have the highest response to ATG, although responses are observed in some patients with normo/hypercellular BMs. Of note, when compared with previous studies, a higher proportion of patients (55%) in this study had a hypocellular BM, which suggests a physician bias towards the use of ATG therapy in this cohort of patients.…”

“…7 The observation that patients with RARS may respond to ATG has since been also described by others. 14,15 While hematological responses were observed in four patients with RAEB, three of these only had a transient response with the patients subsequently progressing to more advanced disease. When compared with the other 11 patients in the study with RAEB who did not respond to ATG, there was no significant difference in OS (P ¼ 0.47).…”

“…In particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin, induces hematological responses in up to 60% of MDS patients. 7,[13][14][15][16][17] ATG is known to react with a number of cell types that include T cells and natural killer cells, as well as molecules modulating the immune response, such as integrins and certain chemokine receptors. 18 While its precise mechanism of action remains unclear, it is believed to involve the amelioration of lymphocyte-mediated suppression of the BM environment.…”

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome

“…2,3 Investigations of immunosuppressive therapies have shown that a subset of MDS patients experience sustained erythroid improvement with response rates ranging from 15 to 45%. [4][5][6][7][8][9][10][11][12] Univariant and multivariant statistical analyses have identified clinical and biological features associated with clinical response to immunosuppressive therapy, which served as the basis for the generation of response predictive models. [4][5][6][13][14][15][16][17][18] In these analyses, bone marrow hypocellularity, HLA-DR15 phenotype, younger age, lower platelet count and shorter duration of transfusion requirement were associated with response to immunosuppressive therapy.…”

Novel therapies for myelodysplastic syndromes

“…54 Immunosuppressive therapy in unselected patients with MDS can lead to sustained increases in red blood cell, neutrophil, and platelet production in 15-30% of pa- tients. 38,55,56 Expression of D-related human leukemic antigen 15 (HLA-DR15; a serologic split of HLA-DR2 that is over represented in MDS, similar to AA), younger age, and shorter duration of red cell transfusion dependence have been identified in multivariate analysis as pretreatment characteristics that correlate with response to immunosuppressive therapy. 57 A paroxysmal nocturnal hemoglobinuria (PNH)-type phenotype has been demonstrated in nearly 20% of patients with RA.…”