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OBJECTIVE: To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). METHODS: Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m~2·d)] and arsenious acid [0.15 mg/(m~2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. RESULTS: Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). CONCLUSION: Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.
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Objective Attempting to create a chemical diversity" combinatorial library consisting of active components of Chinese materia medica compounds. Methods This paper was based on the theory of "thinking and method of 'combinatorial screening' of Chinese material medica compound", using the Qingluo Tongbi Decoction (QTD) which has exact effect against rheumatoid arthritis as system. Re-combination group of the formulation was used and various industrial separation techniques, such as resin and membrane, were used to replace the diversity of combinatorial chemistry synthetic route. Different products were used to establish combinatorial library using "Building Block". Results Different contents of active components in each "Building Block" were found during the establishment of combinatorial libraries. AB-8 resin had good adsorption and desorption functions on sinomenine, and good refined effects on saponin as well. The contents of kirenol were different in each "Building Block" of different combinations. Each "Building Block" had a relative high content of total flavonoids. Conclusion Different combinations and separation techniques lead the differences in types and contents of chemical constituents. So certain pharmacodynamic experiments are needed to evaluate the preparation and to filter out the relevant active "Building Blocks".