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Haematologica 2020 Volume 105(1):102-111
Myelodysplastic Syndromes
Use of immunosuppressive therapy for management of myelodysplastic syndromes: a systematic review and meta-analysis
Maximilian Stahl,1 Jan Philipp Bewersdorf,2 Smith Giri,2 Rong Wang3,4 and Amer M. Zeidan2,3
1Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY; 2Department of Internal Medicine, Section of Hematology, Yale School of Medicine, New Haven, CT; 3Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT and 4Department of Chronic Disease Epidemiology, School of Public Health, Yale University, New Haven, CT, USA
ABSTRACT
Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different immunosuppressive regimens, the lack of high-quality studies, and the absence of validated predictive biomarkers pose important challenges. We conducted a systematic review and meta- analysis according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and searched MEDLINE via PubMed, Ovid EMBASE, COCHRANE registry of clinical trials (CENTRAL), and the Web of Science without language restriction from inception through September 2018, as well as relevant conference proceedings and abstracts, for prospective cohort studies or clinical trials investigating IST in MDS. Fixed and Random-effects models were used to pool response rates. We identified nine prospective cohort studies and 13 clinical trials with a total of 570 patients. Overall response rate was 42.5% [95% confidence interval (CI): 36.1-49.2%] including a complete remission rate of 12.5% (95%CI: 9.3-16.6%) and red blood cell transfusion independence rate of 33.4% (95% CI: 25.1–42.9%). The most commonly used forms of IST were anti-thymo- cyte globulin alone or in combination with cyclosporin A with a trend towards higher response rates with combination therapy. Progression rate to acute myeloid leukemia was 8.6% per patient year (95%CI: 3.3-13.9%). Overall survival and adverse events were only inconsistently reported. We were unable to validate any biomarkers predictive of a therapeutic response to IST. IST for treatment of lower-risk MDS patients can be successful to alleviate transfusion burden and associated sequelae.
Introduction
Myelodysplastic syndromes (MDS) comprise a spectrum of clonal hematopoietic stem cell disorders that are characterized by peripheral blood cytopenias and dys- plastic changes due to ineffective hematopoiesis, recurrent cytogenetic abnormali- ties, and an increased risk of progression to acute myeloid leukemia (AML).1,2 As a heterogenous group of diseases, treatment regimens for MDS patients need to be individualized and mainly based on the extent of MDS-associated symptoms and the risk of progression to AML, as assessed by various risk stratification tools such as the International Prognostic Scoring System (IPSS) and its revised version (IPSS- R).3-5 For patients with lower-risk MDS (which is usually defined as patients with very low, low or intermediate-1 risk based on IPSS and IPSS-R) several treatment options including lenalidomide, erythropoiesis-stimulating agents, immunosup- pressive therapy (IST), and hypomethylating agents are available.3,5-7 The rationale for the use of IST in MDS is based on studies showing that up to 48% of patients with MDS had evidence of autoimmune disease, but the impact of this finding on prognosis is controversial.8,9 Additionally, dysregulation of T-cell function has been linked to impaired hematopoiesis in patients with both aplastic anemia and lower-
Correspondence:
AMER.ZEIDAN
amer.zeidan@yale.edu
Received: February 12, 2019. Accepted: April 15, 2019. Pre-published: April 19, 2019.
doi:10.3324/haematol.2019.219345
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/1/102
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