Antithymocyte Globulin for Treatment of the Bone Marrow Failure Associated with Myelodysplastic Syndromes

Abstract

Although this study was a nonrandomized, single-treatment study, 34% of patients treated with antithymocyte globulin became transfusion independent. Response was associated with a statistically significant longer survival and an almost significant decreased time to disease progression. Treatment with antithymocyte globulin did not seem to be detrimental because historical overall median survival times were similar to those of nonresponders.

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

“…[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. 5,14,19 Analogous to aplastic anemia, elimination of a hematopoietic suppressor T-cell population is hypothesized to underlie treatment response to immunosuppression in this subset of MDS patients. 16,20 Clonal T cells in both MDS and AA can be identified through analysis of the complementarity determining region (CDR)-3 of the T-cell receptor (TCR), which directly binds to antigenic peptides presented in the context of HLA.…”

Novel therapies for myelodysplastic syndromes

“…Dysregulation of the immune response has been implicated and provides the rationale for the use of immunosuppressive agents in MDS, such as antithymocyte globulins (ATG), cyclosporine A, or steroids. [37][38][39] During proliferation, and perhaps through genomic instability, additional molecular abnormalities (bcl-2 overexpression, p53 mutations, Ras mutations and dysfunction, hypermethylation of p15 INK4b ) shift the balance from excessive apoptosis toward maturation arrest and unchecked proliferation of hematopoietic progenitor cells, a process that predominates in more advanced MDS phases (RAEB and RAEB-t). 40,41 …”

“…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.…”

“…58,59 Addition of cyclosporine and/or steroids to ATG does not appear to improve response rates any further. 38 Problems with serum sickness and other toxicities may be significant with ATG and ALG, especially in older patients, empha- sizing the need to select patients carefully for these treatment modalities. 60 …”

Myelodysplasia – therapeutic response to novel therapy and the need for new diagnostic groups

“…Different results were achieved with another distinct single-agent therapy, antithymocyte globulin. 14 In a carefully conducted study, 61 patients with refractory anemia, RAEB, and refractory anemia with ringed sideroblasts, analyzed for morphologic and cytogenetic abnormalities, were treated at the US National Heart, Lung, and Blood Institute with antithymocyte globulin administered intravenously over 4-8 h at a dose of 40 mg/kg daily for 4 days with prednisone. In total, 21 patients (34%) gradually evolved to transfusion independent status, on average 10 weeks after treatment, and were thus deemed responders.…”