Immunosuppressive treatment strategies in low-risk MDS

Abstract

<h2>Summary</h2> Ineffective haematopoiesis with peripheral cytopenias despite normo- or hypercellular bone marrow is the hallmark of the myelodysplastic syndromes especially in the low-risk subgroups. It is caused by increased secretion of inhibitory cytokines in the marrow through a yet unresolved pathophysiological mechanism. Immunoinhibitory or modulatory therapy aims at restoring haematopoiesis by reversing these inhibitory processes and includes antithymocyte globulin (ATG), ciclosporin A (CSA), direct TNF-inhibitors and lenalidomide. Although not yet approved for clinical use, ATG therapy improves mono-, bi- and trilineage cytopenias in around 35–40% of low-risk MDS patients usually after a single treatment course. Highest response rates are seen in younger patients, those with a shorter duration of the disease and low transfusion requirement, with hypocellular bone marrow or with thrombocytopenia. The presence of the HLA-DR15 (DR2) genotype is an additional parameter predicting a response. In contrast, differentiation defects with an increased blast cell percentage or sideroachrestic changes characterize the poor responders. A simple scoring system, using age, duration of transfusion dependency, and HLA-DR15 status, has been developed and allows identifying patients with a high, intermediate, or low probability of response to treatment with ATG. Other immunosuppressive agents which can also induce responses, e.g. CSA, have been combined with ATG, but have not yet been fully evaluated for their potential role in the treatment of MDS. Lenalidomide has a superior efficacy in the 5q-syndrome, but also some efficacy in the other low-risk MDS patients. Further clinical trials are needed to define the potential of immunosuppressive/modulatory treatment in MDS.