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Objective:To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) versus CAG regimen combined with decitabine (DAC) in elderly patients with relapsed acute myeloid leukemia (AML).Methods:From January 2018 to August 2020, the clinical data of forty-five elderly patients with relapse AML at the First Affiliated Hospital of Soochow University were retrospectively analyzed, including 31 males and 14 females. The median age was 66 (60-80) years old. Eighteen patients were administrated with VEN and AZA, while the other 27 were in CAG with DAC. The complete remission (CR) rate, partial remission (PR) rate, total remission rate (ORR), adverse events and overall survival (OS) were compared between the two groups.Results:At the end of the treatment, the ORR in VEN with AZA group was 77.8% (14/18); including 11 CR and 3 PR. In CAG with DAC group, the ORR was 37.0% (10/27); including 8 CR and 2 PR ( P=0.007). Subgroup analysis suggested that VEN with AZA had a higher ORR in patients stratified as intermediate and poor-risk ( P=0.013) or with DNA methylation mutations ( P=0.007). Main adverse events in both groups were bone marrow suppression, infections, nausea and vomiting, anorexia and fatigue. Grade Ⅲ-Ⅳ cytopenia developed in lower incidence of VEN with AZA group, such as leukopenia (66.7% vs. 100%, P=0.002), anemia (50.0% vs. 92.6%, P=0.002), thrombocytopenia (72.2% vs. 96.3%, P=0.031) and neutropenia (61.1% vs. 92.6%, P=0.014). In addition, less grade Ⅲ-Ⅳ infections occurred in VEN with AZA group (66.7% vs. 33.3%, P=0.028), as well as grade Ⅲ-Ⅳ gastrointestinal events (40.7% vs. 11.1%, P=0.032), grade Ⅲ-Ⅳ fatigue (55.6% vs.11.1%, P=0.003) compared with CAG with DAC group. The 1-year OS in VEN with AZA group versus CAG with DAC group was 42.9% and 31.6% respectively ( P=0.150). Conclusion:VEN combined with AZA proves favorable efficacy and tolerablity in elderly patients with relapsed AML.
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Aiming to solve the poor compactibility of the alcoholic extract of Zingiberis Rhizoma(ZR), this study explored the feasibility of its physical modification using co-spray drying with a small amount of hydroxypropyl methyl cellulose(HPMC). Based on the univariate analysis, the influence of two independent variables(the HPMC content in the product and the solid content of spray material) on the powder properties and tablet properties of the dried product was investigated by the central composite design. With the tensile strength and disintegration time of the tablets as the evaluation indexes, the optimal prescription was determined as follows: the HPMC content was 15% and the solid content of spray material was 25.6%. The accuracy of the regression model established for predicting tensile strength and disintegration time of tablets was verified, and the results revealed that the measured values were close to the predicted ones with deviations of 0.47% and-8.2%, indicating good prediction and reproducibility of the model. The tensile strength(4.24 MPa) of tablets prepared with the optimal prescription was 3.59 times that(1.18 MPa, far lower than the baseline of 2 MPa for qualified tablets) with the spray-dried powder of the ZR. On the other hand, due to the addition of HPMC, the disintegration time of tablets increased from 7.3 min to 24.6 min. On the whole, this study provided a new strategy to solve the common problem of poor compactibility of raw Chinese medicinal materials, which facilitated the successful preparation of Chinese medicinal tablets with high drug loads.
Subject(s)
Ginger , Plant Extracts , Reproducibility of Results , Rhizome , Spray DryingABSTRACT
Objective:To evaluate the outcomes and prognostic factors of myelodysplasia syndrome with excess blasts (MDS-EB) patients on intensive chemotherapy or hypomethylating agent treatment prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 108 MDS-EB patients undergoing allo-HSCT from April 2015 to September 2019 were collected retrospectively, intensive chemotherapy or hypomethylating agent treatment (IC/HAM) group, n=72; support care (SC) group, n=36. Clinical outcomes and prognostic risk factors were analyzed. Results:Intensive chemotherapy or hypomethylating agent treatment pre-HSCT had no effects on overall survival (OS) ( P=0.725), relapse-free survival (RFS)( P=0.658), cumulative incidence rate (CIR) ( P=0.121) or non-relapse mortality (NRM)( P=0.236). Univariate and multivariate analysis of an entire cohort showed that poor cytogenetics was an independent risk factor for OS ( P=0.005), DFS ( P=0.001) and CIR( P=0.032); grade Ⅱ-Ⅳ acute graft venous host disease was independently correlated with unfavorable DFS( P=0.004). Conclusions:IC/HAM treatment pre-HSCT fails to yield discrepant post-HSCT outcomes in MDS-EB patients. The pooling of more patients in a well-designed multi-center clinical trial will further demonstrate the efficacy of treatment pre-HSCT in MDS-EB patients.
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Objective@#To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML).@*Methods@#The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared.@*Results@#There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS (HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS (HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse (HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS (HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS (HR = 2.308, 95%CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05).@*Conclusions@#The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor.
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Objective:To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML).Methods:The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared.Results:There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS ( HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS ( HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse ( HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS ( HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS ( HR = 2.308, 95% CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05). Conclusions:The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor.
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Objective@#To explore the impact on efficacy and prognosis of low-risk and intermediate-risk acute myeloid leukemia (AML, non-M3) patients with complete remission (CR) treated by high-dose cytarabine (HD-Ara-C) or standard-dose cytarabine(SD-Ara-C) before haploidentical hematopoietic stem cell transplantation (Haplo-HSCT).@*Methods@#A retrospective analysis was performed on 71 low-risk and intermediate-risk adult AML patients in the First Affiliated Hospital of Soochow University from March 2008 to April 2017. All the patients were treated by consolidation regimens containing cytarabine before Haplo-HSCT. According to the dosages of cytarabine, the patients were divided into HD-Ara-C group and SD-Ara-C group. Kaplan-Meier method, log-rank test and Cox regression model were used to make survival analysis, and the prognosis and efficacy between the two groups were compared.@*Results@#Of the 71 patients, 43 were male and 28 were female, and the median age was 37 years (18-56 years). The median follow-up time was 39 months (6-119 months). Sixty-four patients were in first remission, and 7 patients were in second remission. At the end of follow-up, the 2-year cumulative incidence of recurrence (CIR), overall survival (OS) rate, progression-free survival (PFS) rate, and non-recurrent death (NRM) rate in SD-Ara-C group were 19.33%, 77.44%, 80.67%, and 17.29%, respectively, the 2-year CIR, OS rate, PFS rates and NRM rate in HD-Ara-C group were 6.29%, 79.90%, 93.71%, and 17.68%, respectively. There was no significant difference in CIR (P = 0.124), OS rate (P = 0.862), PFS rate (P = 0.124) and NRM rate (P = 0.734) between the two groups. The incidence of severe infection in HD-Ara-C group was higher than that in SD-Ara-C group after consolidation therapy [62.8% (22/35) vs. 27.8% (10/36), P = 0.03].@*Conclusion@#Compared with SD-Ara-C, the consolidation therapy containing HD-Ara-C before Haplo-HSCT cannot significantly improve the prognosis of low-risk and intermediate-risk AML patients in CR, but would increase the risk of severe infection after intensive consolidation therapy.
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Objective To explore the impact on efficacy and prognosis of low-risk and intermediate-risk acute myeloid leukemia (AML, non-M3) patients with complete remission (CR) treated by high-dose cytarabine (HD-Ara-C) or standard-dose cytarabine(SD-Ara-C) before haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Methods A retrospective analysis was performed on 71 low-risk and intermediate-risk adult AML patients in the First Affiliated Hospital of Soochow University from March 2008 to April 2017. All the patients were treated by consolidation regimens containing cytarabine before Haplo-HSCT. According to the dosages of cytarabine, the patients were divided into HD-Ara-C group and SD-Ara-C group. Kaplan-Meier method, log-rank test and Cox regression model were used to make survival analysis, and the prognosis and efficacy between the two groups were compared. Results Of the 71 patients, 43 were male and 28 were female, and the median age was 37 years (18-56 years). The median follow-up time was 39 months (6-119 months). Sixty-four patients were in first remission, and 7 patients were in second remission. At the end of follow-up, the 2-year cumulative incidence of recurrence (CIR), overall survival (OS) rate, progression-free survival (PFS) rate, and non-recurrent death (NRM) rate in SD-Ara-C group were 19.33%, 77.44%, 80.67%, and 17.29%, respectively, the 2-year CIR, OS rate, PFS rates and NRM rate in HD-Ara-C group were 6.29%, 79.90%, 93.71%, and 17.68%, respectively. There was no significant difference in CIR (P＝0.124), OS rate (P＝0.862), PFS rate (P＝0.124) and NRM rate (P＝0.734) between the two groups. The incidence of severe infection in HD-Ara-C group was higher than that in SD-Ara-C group after consolidation therapy [62.8% (22/35) vs. 27.8% (10/36), P＝ 0.03]. Conclusion Compared with SD-Ara-C, the consolidation therapy containing HD-Ara-C before Haplo-HSCT cannot significantly improve the prognosis of low-risk and intermediate-risk AML patients in CR, but would increase the risk of severe infection after intensive consolidation therapy.
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BACKGROUND: Patients with osteoporosis are prone to develop fractures, and moreover some patients are first diagnosed with osteoporosis because of a fragility fracture. Therefore, it is critical to understand the correlation between osteoporotic medications and fracture healing. OBJECTIVE: To summarize the effect of anti-osteoporosis medications on osteoporotic fracture healing in order to promote its clinical application. METHODS: A computer-based online search of PubMed, CNKI, VIP and WanFang databases between January 2012 and July 2016 was performed to retrieve the related articles with the keywords of "osteoporotic fracture, healing, bone nutrition supplements, anti-resorptive agents, anabolic agents, dual effect agents, new targeted agents" in English and Chinese, respectively. Literature concerning the effect of anti-osteoporosis medications on fracture healing was selected, and the articles published lately in authoritative journals were preferred. RESULTS AND CONCLUSION: Most of anti-osteoporotic medications have no harmful influence on fracture healing, including bone nutrition supplements (calcium and vitamin D), anti-resorptive agents (bisphosphonate, denosumab, estrogen and selective estrogen receptor modulators, statins and calcitonin), anabolic agents (parathyroid hormone), and dual effect agents (strontium ranelate). Calcium and vitamin D are the basic drugs; anti-resorptive agents exert overt anti-osteoporotic effect; and the new targeted agents like cathepsin K inhibitor and sclerostin monoclonal antibody provide more choices for the therapy of osteoporotic fracture. Partial anti-osteoporotic agents inhibit the viability of osteoclasts, so their early application may be against fracture healing. The optimal time of anti-osteoporotic medications and the effect on acute and non-acute osteoporotic fractures need to be further explored.
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OBJECTIVE: To investigate the effect of spearmint oil given at different period of time on pathological changes and the expression of tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), matrix metalloproteinases-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and α-smooth muscle actin(α-SMA) in mice with bleomycin-induced pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intratracheal instillation of bleomycin in ICR mice, then the animals were randomly divided into spearmint oil therapeutic and preventive groups. One day after intratracheal instillation of bleomycin, the mice in preventive group were treated with spearmint oil for 4 weeks; while those in therapeutic groups were given spearmint oil 8 days after administering of bleomycin for 3 weeks. The body weight and mortality were recorded every week; the pathologic changes of lung tissue were observed by HE and Masson staining; the hydroxyproline content was determined; the levels of TNF-α, TGF-β1, MMP-9 and TIMP-1 were measured by ELISA; the expression of α-SMA was observed by immunochemistry. RESULTS: In the preventive groups, spearmint oil of 14, 42 and 140 mg · kg-1 significantly decreased the fibrosis area and reduced collagen deposition while preserving some alveolar structure; spearmint oil of 14 and 140 mg · kg-1 significantly decreased hydroxyproline, TGF-β1 and MMP-9 content; spearmint oil of 14, 42, 140 mg · kg -1 significantly attenuated the expression of α-SMA. In the therapeutic groups, spearmint oil had no significant effect except that the 14 mg · kg-1 group obviously attenuated the expression of α-SMA. CONCLUSION: Spearmint oil given at early period attenuates bleomycin-induced pulmonary fibrosis in mice, the mechanism may include decreasing basemembrane disruption, inhibiting fibroblast, proliferation and transformation, reducing the expression of α-SMA as well as the formation and accumulation of ECM through decreasing the contents of MMP-9 and TGF-β1 in lung tissue. Copyright 2012 by the Chinese Pharmaceutical Association.
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<p><b>BACKGROUND</b>Because of the complexity and severity of the surgery and its associated complications, pancreaticoduodenectomy (PD) is associated with significant morbidity and mortality, especially the hemorrhage post-PD. Exploring the factors associated with post-PD hemorrhage is very important for the patients' safety.</p><p><b>METHODS</b>Clinical data from 303 cases of PD between January 1998 and December 2008 were analyzed retrospectively.</p><p><b>RESULTS</b>The overall mortality rate was 4.95% (15/303). However, post-operative bleeding occurred in 25 patients (8.25%) with nine episodes resulting in death (36.00%). Univariate analysis was performed and identified tumor size, Child's classification, total pancreatic uncinatic process resection, and pancreatic leakage as significant risk factors for post-PD hemorrhage. In the severe hemorrhage group, incomplete resection of uncinate process of pancreas and pancreatic leakage were the main causes. The multivariate Logistic regression analysis revealed that each of these variables is an independent risk factor.</p><p><b>CONCLUSIONS</b>Primary prevention of bleeding complications depends on total pancreatic uncinatic process resection and meticulous hemostatic techniques during surgery. In addition, several peri-operative factors were found to contribute to post-PD bleeding.</p>
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Female , Humans , Male , Middle Aged , Pancreaticoduodenectomy , Mortality , Postoperative Hemorrhage , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To explore the factors of post pancreatoduodenectomy hemorrhage.</p><p><b>METHODS</b>The clinical data of 263 cases between January 1998 and April 2008 underwent pancreatoduodenectomy were analyzed prospectively.</p><p><b>RESULTS</b>The overall mortality rate was 4.94% (13/263). Postoperative bleeding occurred in 23 patients (8.75%), with 8 episodes ending fatally (34.8%). The tumor size, Child classification, caput total resection and pancreatic leakage were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. The multivariate Logistic regression analysis revealed that all of the five factors turned out to be the independent risk factors.</p><p><b>CONCLUSIONS</b>The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. The pancreatic leakage is also one of the most important factors due to postoperative bleeding. The prophylactic use of somatostatin is not necessary.</p>