Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome
Introduction
Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders characterized by inefficient hematopoiesis, hypercellular bone marrow, dysplasia of blood cells, and cytopenias. It is well known that MDS had been an intractable disease for which the mainstream therapeutic approach was best supportive care but not intensive chemotherapy [1]. The only potential curative option for MDS is hematopoietic cell transplantation, which is suitable for only a few patients [2]. Recently, however, treatment of MDS has benefited from advances in molecular targeted drug discovery, such as the decitabine (DAC), and from the reappraisal of forgotten drugs such as thalidomide, for multiple myeloma.
Aberrant DNA methylation has been implicated in the pathogenesis of many tumors including myelodysplastic syndrome (MDS). Hypomethylating agents like DAC have indicated anti-MDS activity [3], [4]. Administered DAC is active in patients with MDS, resulting in improvements of progression-free survival (PFS), quality-of-life, and AML transformation [5]. However, response rates to these agents remain low, with complete response (CR) observed in fewer than 10% of patients in randomized studies [4]. There were no significant survival advantages observed with DAC over best supportive care.
Thalidomide exerts a broad spectrum of pharmacological and immunological effects, such as down-regulation of tumor necrosis factors alpha, up-regulation of adhesion molecules, and inhibition of angiogenesis. As an inexpensive and relatively low toxicity agent, thalidomide is regarded as a promising therapeutic candidate, especially for malignant diseases [6]. Treatment with thalidomide has been shown to improve anemia and long-term survival for patients with MDS [7]. Approximately one-third of the patients had decreases in bone marrow blasts of 50% after a maintenance thalidomide-based combination therapy [8]. But, thalidomide remains a possible therapeutic option only for select MDS patients, such as those with earlier stage disease, those with younger age, and those with anemia as the only significant blood cytopenia [9].
Considering the heterogeneity of nosographic entities representing MDS, risk stratification [10] is essential to target the treatment according to the risk of AML evolution and blood transfusion requirement. Oral maintenance thalidomide therapy combined with chemotherapy is promising. At the time, we still did not know whether thalidomide plus DAC provided benefits to elderly patients with risk-tailored MDS. In the study, we continued to represent the multicenter study reviews that came from China to evaluate the efficacy and adverse events of maintenance thalidomide plus DAC chemotherapy for elderly patients with MDS.
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Study population
This was an open-label, prospective, observational assessment conducted from January 2011 to February 2014. Patients were required to have histologically documented MDS, as defined by the WHO 2008 classification [11]. Newly diagnosed MDS patients were evaluated to determine the cytogenetic stratification and their detection rate by chromosomal study and fluorescent in situ hybridization (FISH) technique separately.
A total of 107 untreated elderly patients (age 60–82 years old) provided written
Patient characteristics
A total of 107 patients (age range 60–82 years old) were treated. 32 of 107 patients (29.9%) matched the low risk profile, and 75/107 patients (70.1%) fit the high risk characteristics. Baseline clinical characteristics between the two cohorts were balanced in age (median 66 years old), sex distribution, risk profile, and WBC counts (P > 0.05, Table 1).
Response to therapy
107 elderly patients received DAC or DAC + thalidomide regimen as front-line therapy. 35/52 patients (67.3%) with DAC therapy reached overall
Discussion
Myelodysplastic syndromes are generally diseases of older people. In 2003, male prevalent patients were on average 9 years younger than females, with median ages of 69 and 78, respectively [17]. Most patients are diagnosed in their late 60s to early 70s. MDS is a risk factor for the development of acute myeloid leukemia, which can occur in 10–15% of patients with MDS. In the findings, the median age of enrolled patients was 66 years old. High risk patients (IPSS intermediate-2 or high) occupied
Conflict of interest statement
I would like to declare on behalf of my co-authors that this work is original research that has not been published previously and is not under consideration for publication elsewhere, either in part of in whole. All the authors listed have approved the manuscript that is enclosed.
Acknowledgments
We would like to thank all the patients and the clinicians from the participating sites. This work was supported by grants from the National Natural Science Foundation of China (No. 81460027), the Natural Science Foundation of Inner Mongolia (No. 2013MS1157) and Inner Mongolia Autonomous Region Health and Family Planning health research projects (No. 201302059). All authors discussed the results and commented on the manuscript.
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These authors equally contributed to this work.