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ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.
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OBJECTIVE@#To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients.@*METHODS@#Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups.@*RESULTS@#The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01).@*CONCLUSIONS@#QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.
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Humans , Aged , Arsenic/therapeutic use , Powders/therapeutic use , Retrospective Studies , Leukemia, Myeloid, Acute/drug therapy , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
OBJECTIVE@#To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC).@*METHODS@#Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed.@*RESULTS@#Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05).@*CONCLUSION@#QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
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Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antineoplastic Agents , Therapeutic Uses , Arsenicals , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Leukemia, Myeloid, Acute , Drug Therapy , Mortality , Powders , Retrospective StudiesABSTRACT
Objective To investigate the clinical effects of Qinghuang powder, low-intensity chemotherapy and Qinghuang powder alternated with low-intensity chemotherapy in the treatment of elderly acute myeloid leukemia patients progressed from myelodysplastic syndromes (MDS-AML). Methods A total of 32 elderly patients with MDS-AML treated in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2014 to December 2017 were retrospectively analyzed. Of them, 12 patients received Qinghuang powder (Qinghuang powder group), 6 patients received Qinghuang powder alternated with low-intensity chemotherapy (alternating group), and 14 patients received low-intensity chemotherapy (low-intensity chemotherapy group), based on the real world of patient's voluntary choice of treatment. The efficacy and adverse reactions in the 3 groups were observed. Results The overall response number of Qinghuang powder, alternating, and low-intensity chemotherapy groups were 2, 2 and 4 cases, respectively, there was no significant difference among the 3 groups (P＞ 0.05). The median overall survival time of 3 groups were 14, 12 and 8 months, respectively, there was no significant difference among the 3 groups (P＞ 0.05). Two cases in Qinghuang powder group presented with gastrointestinal reactions; 3 cases in alternating group with myelosuppression, 2 cases with liver function damage, and 2 cases with gastrointestinal reaction; 11 cases in low-intensity chemotherapy group presented with bone marrow suppression, 3 cases with liver function damage, 7 cases with gastrointestinal reactions, and 2 cases with myocardial enzyme changes. The incidences of myelosuppression, liver function damage and myocardial enzyme changes in Qinghuang powder group were lower than those in the alternating group and low-intensity chemotherapy group. Conclusion The efficacy of Qinghuang powder or Qinghuang powder alternated with low-intensity chemotherapy for the treatment of elderly MDS-AML is not worse than the low-intensity chemotherapy, furthermore Qinghuang powder or Qinghuang powder alternated with low-intensity chemotherapy has fewer adverse reactions and better tolerance.
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Objective@#To investigate the clinical effects of Qinghuang powder, low-intensity chemotherapy and Qinghuang powder alternated with low-intensity chemotherapy in the treatment of elderly acute myeloid leukemia patients progressed from myelodysplastic syndromes (MDS-AML).@*Methods@#A total of 32 elderly patients with MDS-AML treated in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2014 to December 2017 were retrospectively analyzed. Of them, 12 patients received Qinghuang powder (Qinghuang powder group), 6 patients received Qinghuang powder alternated with low-intensity chemotherapy (alternating group), and 14 patients received low-intensity chemotherapy (low-intensity chemotherapy group), based on the real world of patient's voluntary choice of treatment. The efficacy and adverse reactions in the 3 groups were observed.@*Results@#The overall response number of Qinghuang powder, alternating, and low-intensity chemotherapy groups were 2, 2 and 4 cases, respectively, there was no significant difference among the 3 groups (P > 0.05). The median overall survival time of 3 groups were 14, 12 and 8 months, respectively, there was no significant difference among the 3 groups (P > 0.05). Two cases in Qinghuang powder group presented with gastrointestinal reactions; 3 cases in alternating group with myelosuppression, 2 cases with liver function damage, and 2 cases with gastrointestinal reaction; 11 cases in low-intensity chemotherapy group presented with bone marrow suppression, 3 cases with liver function damage, 7 cases with gastrointestinal reactions, and 2 cases with myocardial enzyme changes. The incidences of myelosuppression, liver function damage and myocardial enzyme changes in Qinghuang powder group were lower than those in the alternating group and low-intensity chemotherapy group.@*Conclusion@#The efficacy of Qinghuang powder or Qinghuang powder alternated with low-intensity chemotherapy for the treatment of elderly MDS-AML is not worse than the low-intensity chemotherapy, furthermore Qinghuang powder or Qinghuang powder alternated with low-intensity chemotherapy has fewer adverse reactions and better tolerance.
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OBJECTIVE@#To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS).@*METHODS@#Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed.@*RESULTS@#After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 μ g/L (P0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, μ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, μ g/L, P<0.05).@*CONCLUSION@#QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.
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OBJECTIVE@#To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula.@*METHODS@#All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data.@*RESULTS@#The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions.@*CONCLUSIONS@#QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.
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Female , Humans , Male , Middle Aged , Arsenicals , Pharmacology , Therapeutic Uses , Cell Lineage , DNA Methylation , Demethylation , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Gene Ontology , Leukocyte Disorders , Drug Therapy , Genetics , Powders , Treatment OutcomeABSTRACT
Objective To investigate the survival of oral arsenic-containing Qinghuang Powder (QHP) and low intensive chemotherapy (LIC) in the treatment of elderly patients with acute myeloid leukemia (AML).Methods Forty-two AML patients older than 60 years in Xiyuan Hospital from January 2015 to December 2017 were retrospectively analyzed.Of them,20 cases were treated with QHP (QHP group),22 cases were treated with LIC (LIC group).The survivals of the two groups were compared.Results There was no significant difference of median survival time (13 months vs.13.5 months,x2 =0.096,P =0.757),1-year survival rates (59.1％ vs.70.0 ％,x2 =0.543,P =0.461),2-year survival rates (13.6 ％ vs.15.0 ％,x2 =0.016,P ＞ 0.05),and 3-year survival rates (4.6 ％ vs.5.0 ％,x2 =0.005,P ＞ 0.05) between LIC and QHP groups.There was no significant difference of median survival time in age ≥75 year (12 months vs.12.5 months,x2 =1.317,P =0.251),performance status scores ＞ 2 (12 months vs.12 months,x2 =0.834,P =0.361),hematopoietic stem cell transplantation with combined disease index ＞ 2 (12 months vs.13 months,x2 =1.726,P =0.189),secondary AML (10 months vs.14 months,x2 =1.552,P =0.213),and poor cytogenetics (12 months vs.8 months,x2 =0.479,P =0.489) between LIC and QHP group.Conclusion The survival of elderly AML patients is considerable in patients treated with oral QHP and LIC,which suggests that oral QHP may be an equivalent alternative treatment since elderly AML (especially more than 75 years) patients refused to LIC therapy.
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Objective To evaluate the safety of compound Qinghuang powder for myelodysplastic syndromes(MDS). Methods A total of108 patients with MDSwere collected, 60 patients were treated with Qinghuang powder(Qinghuang powder group)and 48 with compound Qinghuang powder(compound Qinghuang group). The treatment time of 3 months was as one course, and all the patients were treated for more than one course. The patients who developed adverse reactions in the Qinghuang powder group changed to receive compound Qinghuang powder. The adverse reactions were recorded during the treatment. Results The overall incidence of adverse reactions in the compound Qinghuang powder group was significantly lower than that in the Qinghuang powder group(18.75% vs. 41.7%; χ2=6.492, P<0.05). None in the compound Qinghuang powder group and 3 patients in the compound Qinghuang powder group developed moderate to severe adverse reactions. The incidences of various adverse reactions in the compound Qinghuang powder group were lower than those in the Qinghuang powder group, especially, lower limb swelling (4.17%vs. 25%;χ2=9.205, P<0.05) epigastric discomfort(18.75% vs. 41.67%; χ2=6.492, P<0.05). Twenty patients who developed adverse reactions in the Qinghuang powder group changed to receive compound Qinghuang powder. Among them, 5 patients (25%) maintained adverse reactions. The various adverse reactions after changing to compound Qinghuang powder were decreased, especially, facial swelling (10% vs. 30%; χ2=2.50, P<0.05), leg swelling (5%vs. 45%;χ2=8.533, P<0.05), and abdominal pain and diarrhea(10%vs. 30%;χ2=2.50, P<0.05). No patient developed liver or kidney dysfunction after the treatment with Qinghuang powder or Compound Qinghuang powder. Conclusion Compound Qinghuang powder is safer than Qinghuang powder in the treatment of MDS.
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The myelodysplastic syndromes (MDS) are a group of clonal heterogeneous disorders of hematopoietic/progenitor.There are differences between Chinese and Western on cytogenetic typing of MDS.The arsenic-containing Chinese herbal formula Qinghuang powder is exact effective in the treatment of MDS.The clinical effect mechanism research indicated that treatment with arsenic-containing Chinese herbal formula had no effect on karyotype status,but resulted in a significant genome wide demethylation.The effective arsenic-concentration in blood is (19.39±10.36) μg/L,which is obviously lower than that in treating APL.
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Objective To verify the clinical effect of Qinghuang powder in chronic myelogenous leukemia(CML). Methods 86 CML patients treated with Qinghuang powder, in which 28 cases also partially received herbal medicine (activating blood circulation to dissipate blood stasis). Results 62 cases had complete remission (72.1%), 14 cases partial remission (16.3 %), advance 8 cases(9.3 %), inefficiency 2 cases (2.3 %), and the total efficiency was 97.7 %. The symptom were improved after a week when patients had taken medicines. 44 cases have hepatomegalia, among them 39 cases have diminished or became normal compared to untreated. 70 cases have splenoparectasis, among them 60 cases became normal, 9 cases diminished, and 1 case had no change after treatment. It took 15.5 days in average when spleen began to diminish, and took 62.9 days to become smallest. The WBC began to decrease at 10.4 day and took 54.8 days in average became normal. The major side effect was digestive tract symptom, followed by skin pigmentation and skin excessive cornification. It could be avoided by low dosage. Conclusion Qinghuang powder could not only induce CML to CR, but also improve the clinical symptom of CML and eliminate the infiltration of leukemia cells. It has little influence to Hb and Plt.