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Immunosuppressive therapy in myelodysplastic syndromes
risk MDS and can potentially be restored by IST.9-11 Several forms of IST have been tested in MDS treatment with varying degrees of success. Previous studies have reported durable objective responses and transfusion independence ranging up to 55% and 27%, respectively.12,13 Consensus guidelines recommend consideration of IST in patients with low or intermediate-1 risk, non-del(5q-) MDS patients.3,6,14 The most commonly used of these are anti- thymocyte globulin (ATG), cyclosporine A (CsA), and monoclonal antibodies (etanercept, alemtuzumab) which can be used either as monotherapy or in combination.13,15- 20 Although IST has been used for over two decades in MDS treatment, response rates are highly heterogeneous
between various patient subpopulations and studies. While several predictive response markers such as age, HLA-DR15 positivity, bone marrow cellularity, and dis- ease duration have been identified in some studies, these findings could not be reproduced in others.12,16,21-23
Given this large heterogeneity among published studies, we performed a systematic literature review and meta- analysis on several forms of IST in MDS to objectively assess overall response rates (ORR), rates of achieving a complete remission (CR), erythroid hematologic improve- ment (HI-E), and red blood cell transfusion independence (TI) as well as the rate of AML progression per patient- year for patients receiving IST.
Figure 1. Flow chart showing study selection as per the MOOSE guidelines. The search strategy and stepwise process of study selection used in this meta-analysis. MEDLINE via PubMed, Ovid EMBASE, the COHRANE registry of clinical trials (CENTRAL), and the Web of Science electronic databases were searched with no lan- guage restriction from inception through September 2018, using the following combination of free-text terms linked by Boolean operators: (“MDS” OR “myelodyspla- sia” OR “myelodysplastic syndrome”) AND (“IST” OR “immunosuppressive therapy” OR “immunosuppression” OR “ATG” OR “anti-thymocyte globulin” OR “tacrolimus” OR “cyclosporine” OR “sirolimus” OR “prednisone” OR “prednisolone” OR “steroids” OR “etanercept” OR “alemtuzumbab”). Two authors (MS and JPB) independently screened the titles and abstracts of all retrieved studies for eligibility and removed any duplicate records. In a second step, full texts of the potentially eligible studies were reviewed for the final eligibility. Review, basic science articles and articles with insufficient patient number (< 5 patients) as well as preliminary studies and ret- rospective studies were excluded.
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