Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Efficacy and safety of AZA combined with HHT and LDAC in the treatment of acute myeloid leukemia patients with 3+ 7 conventional regimen intolerance / 中国医师杂志

Objective:To evaluate the efficacy and safety of azacytidine (AZA) combined with homoharringtonine (HHT) and low-dose cytarabine (LDAC) in the treatment of acute myeloid leukemia (AML) patients with 3+ 7 conventional regimen intolerance.Methods:A retrospective analysis was conducted on the clinical characteristics, efficacy, prognosis, and adverse events of 33 AML patients (15 initially diagnosed and 18 relapsed/refractory) admitted to the Second Xiangya Hospital of Central South University.Results:Among the 33 AML patients treated with this regimen, the median age was 55 years old, 9 patients had a moderate cytogenetic risk, and 18 patients had a high cytogenetic risk. Among the 33 patients, 3 were lost to follow-up and 1 had incomplete data. Among the remaining 29 patients who received AZA+ HHT+ LDAC treatment, the total complete response (CR) rate was 69.0%(20/29), and the total response rate (ORR) was 79.3%(23/29); The median progression free survival (PFS) was 7.0 months. Among the subgroup analysis, including age, gender, Eastern Cooperative Oncology Group (ECOG) score, disease classification, bone marrow progenitor cells, peripheral blood leukocytes, risk stratification, and epigenetic abnormalities, only CR rates and PFS differences were statistically significant among different ECOG scoring groups ( P=0.048; P=0.021). A total of 29 patients underwent 69 AZA+ HHT+ LDAC chemotherapy cycles. Retrospective grading was performed on 69 cycles based on common toxicity criteria for adverse events (CTC AE version 5.0). The most common grade Ⅲ-Ⅳ hematological adverse events were thrombocytopenia (54/69, 78.3%) and granulocytopenia (48/69, 69.6%). Common non hematological adverse events included nausea (19/69, 27.5%), infection (17/69, 24.6%), and hypokalemia (18/69, 26.1%). Conclusions:AZA combined with HHT and LDAC has a good therapeutic effect in the treatment of acute myeloid leukemia, and adverse reaction events are controllable.

Miopericarditis inducida por altas dosis de citarabina: cuando el corazón se debilita, pero la lucha contra el cáncer se fortalece / High dose cytarabine induced myopericarditis: When the heart debilitates but the fight against cancer must be strong

Resumen La cardiotoxicidad por citarabina es un efecto adverso poco conocido. Se presenta el caso de un paciente de 51 años con antecedentes de Leucemia Mieloide Aguda manejada con altas dosis de citarabina y que presentó como consecuencia miopericarditis aguda. Luego del manejo de soporte en cuidados intensivos, se inició tratamiento cardioprotector específico para falla cardiaca y, dada la alta posibilidad de requerir citarabina en el manejo oncológico ulterior, se inició tratamiento con antinflamatorios no esteroideos y colchicina con el fin de reducir el riesgo de recurrencia de la miopericarditis. Se presenta el caso clínico, y una estrategia diagnóstica para pacientes con altas dosis de citarabina y compromiso pericárdico y miocárdico.

Summary Knowledge about cytarabine induced cardiotoxicity is scarce. We present the clinical case of a 51-year-old patient with past medical history of Acute Myeloid Leukemia managed with high doses of cytarabine and who developed acute myopericarditis as a complication. After support management in intensive care unit, specific cardioprotective heart failure therapy was started and, due to the high possibility of requiring high doses of cytarabine in subsequent oncological management, therapy with Non-Steroidal Anti-inflammatory drugs and colchicine was given to reduce the risk of myopericarditis recurrence. We present the clinical case and a diagnostic strategy for patients with high doses of cytarabine and pericardial and myocardial involvement.

Reacción adversa a Citarabina con compromiso cutáneo: reporte de caso / Adverse reaction to Cytarabine with skin involvement: case report: case report

RESUMEN Presentamos el caso de una paciente de 67 años con un diagnóstico clínico de reacción adversa cutánea al uso del agente quimioterapéutico citarabina, el cual recibió en el contexto del tratamiento médico por leucemia mieloide aguda. Se realiza la descripción epidemiológica, signos clínicos, evolución médica y realizamos la comparación con casos similares previamente descritos. Para excluir otros diagnósticos diferenciales se realizó estudio histopatológico y su correlación con el examen clínico.

ABSTRACT We report the case of a 67-year-old female patient with a medical diagnosis of cutaneous adverse reaction to the use of the chemotherapeutic agent cytarabine, which she received in the context of medical treatment for acute myeloid leukemia. Epidemiological description, clinical signs, medical evolution, and comparison with similar cases previously described. In order to exclude other differential diagnoses, histopathological study and its correlation with the clinical examination were performed.

Analysis of nosocomial infection after intermediate-high dose cytarabine consolidation theraphy in patients with acute myeloid leukemia / 肿瘤研究与临床

Objective:To investigate the clinical characteristics, influencing factors and prevention and treatment measures of nosocomial infection in patients with acute myeloid leukemia (AML) (non-acute promyelocytic leukemia) after applying intermediate-high dose cytarabine (Ara-C) chemotherapy.Methods:The clinical data of 80 patients with AML treated with intermediate-high dose Ara-C in the Second Hospital of Shanxi Medical University from March 2013 to January 2020 were analyzed retrospectively. The clinical features of nosocomial infection were summarized and the influencing factors of infection were analyzed by using multivariate logistic regression.Results:A total of 80 patients received 198 times of chemotherapy, and the infection rate was 72.7% (144/198). Infection sites mainly included respiratory tract infection, pulmonary infection, gastrointestinal infection. A total of 45 strains of pathogenic bacterias were detected, among which Gram negative bacilli accounted for 55.6% (25/45), Gram positive cocci accounted for 24.4% (11/45), fungi accounted for 8.9% (4/45) and viruses accounted for 11.1% (5/45). There were no significant differences in infection rate, hospitalization time, neutrophils recovery time and hospitalization expenses between the sterile laminar flow ward and the general ward (all P > 0.05). Multivariate logistic regression analysis showed that infection during induction chemotherapy was independent risk factor of infection ( OR = 5.076, 95% CI 1.978-13.022, P =0.001), and antibiotic prevention was independent protective factor of nosocomial infection ( OR = 0.332, 95% CI 0.136-0.803, P = 0.014). Conclusions:The infection rate of AML patients receiving intermediate-high dose Ara-C chemotherapy is high. During the treatment, we should be alert to the infection during induction chemotherapy and use antibiotics to prevent it in time. For patients undergoing intermediate-high dose Ara-C chemotherapy, strengthening the environmental cleanliness of general wards may achieve the same preventive effect as that of sterile laminar flow wards.

Influence of Serum TGF-β1 and EGFR Levels on the Therapeutic Effect of High-Dose AraC in Patients with Acute Myeloid Leukemia Based on the Decision Curve / 中国实验血液学杂志

OBJECTIVE@#To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML).@*METHODS@#98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve.@*RESULTS@#After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone.@*CONCLUSION@#The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.

Resultados de pacientes con linfoma del manto: impacto de terapias basadas en citarabina y trasplante hematopoyético / Cytarabine and hematopoietic cell transplantation for mantle cell lymphoma: analysis of 20 patients

Background: Mantle cell lymphoma (MCL) has high relapse and mortality rates. There is a survival benefit when treatment is intensified with cytarabine (AraC), hematopoietic cell transplantation (HCT) and maintenance with rituximab. Aim: To assess the outcomes of patients with MCL treated in a university hospital. Material and Methods: Review of an oncology center database and medical records identifying patients with MCL treated between 2006 and 2017. Death dates were obtained from the death certificate database of the National Identification Service. We analyzed the response rate, overall survival (OS) and progression-free survival (PFS). As a secondary objective, the survival impact of AraC, HCT and maintenance with rituximab, was also analyzed. Results: Information on 20 patients aged 62 ± 11 years, followed for a median of 45 months was retrieved. Eighty-five percent were diagnosed at an advanced stage. The most used first-line regime was R-CHOP in 11 patients, followed by R-HyperCVAD in five. Only 47% achieved complete response. 4-year PFS and OS were of 30 and 77% respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) significantly predicted PFS and OS. Maintenance with rituximab or HCT was associated with better PFS (48 vs 21 months, p < 0.01). The exposure to AraC or HCT, in refractory or relapsed disease, was associated with an increase in PFS from 9 to 28 months (p = 0,02) and 4-year OS from 40 to 100% (p = 0.05). OS increased even more, from 25 to 100% in those with high-risk MIPI (p = 0.04). Conclusions: The incorporation of AraC, HCT and maintenance with rituximab in the therapeutic backbone of MCL, especially for high-risk cases, was associated with improved survival.

Effects of different doses of cytarabine consolidation therapy followed by haploidentical hematopoietic stem cell transplantation on low-risk and intermediate-risk acute myeloid leukemia patients / 白血病·淋巴瘤

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.

Effect of arsenic trioxide maintenance therapy on long - term recurrence rate in patients with acute promyelocytic leukemia / 中国基层医药

Objective To explore the effect of arsenic trioxide maintenance therapy on the long-term recur-rence rate in patients with acute promyelocytic leukemia ( APL ) . Methods From December 2011 to December 2013,60 patients with APL in the First People's Hospital of Huzhou were selected and divided into control group and observation group according to random number table, with 30 cases in each group. All patients received the same induction therapy and consolidation therapy. During the maintenance treatment period, all - trans retinoic acid ( ATRA) was given to the control group,and arsenic trioxide was used in the observation group. The serum levels and incidence of adverse reactions in the two groups were detected and compared after two cycles of the maintenance therapy. Three years of follow - up was conducted after treatment to record and compare the recurrence rate and survival rate in the two groups. Results The levels of TC and TG after 1 and 2 cycles of treatment were higher than those before treatment in both two groups(all P<0. 05),but the levels of lipid indicators in the observation group were lower than those in the control group,and the differences were statistically significant (t=2. 044,2. 175,all P<0. 05). The incidence rates of retinoic acid syndrome,elevated intracranial pressure and other adverse reactions in the observation group during the treatment were lower than those in the control group(6. 67％ vs. 26. 67％,6. 67％ vs. 30. 00％,6. 67％ vs. 26. 67％),and the differences were statistically significant(χ2 =0. 043,0. 023,0. 043,all P<0. 05). The survival rates after 2 and 3 years of treatment in the observation group were higher than those in the control group(90. 00％ vs. 66. 67％,83. 33％ vs. 60. 00％),and the differences were statistically significant(χ2 =4. 812,4. 812,all P<0. 05). The recurrence rate after 3 years of treatment in the observation group was lower than that in the control group(10. 00％ vs. 33. 33％),and the difference was statistically significant(χ2 =4. 812,P <0. 05). Conclusion For patients with APL, the application of arsenic trioxide in the maintenance therapy can produce no significant effect on their lipid metabolism, and at a certain extent, can help reduce the incidence of adverse reactions and recurrence rate,and improve the survival rate.

Effects of different doses of cytarabine consolidation therapy followed by haploidentical hematopoietic stem cell transplantation on low-risk and intermediate-risk acute myeloid leukemia patients / 白血病·淋巴瘤

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.

Clinical efficacy of combined or single use of clofibrate and cytarabine in treatment of adult patients with myelodysplastic syndromes or acute leukemia: a Meta analysis / 白血病·淋巴瘤

Objective To analyze the clinical efficacy of combined or single use of clofibrate and cytarabine in the treatment of adult patients with myelodysplastic syndromes (MDS) or acute leukemia (AL).Methods Clofarabine combined with cytarabine was used in the combined group and clofarabine or cyarabine alone was used in the control group.All the studies about cytarabine and clofarabine were searched in PubMed,Cochrance Library,Embase,CNKI,Wanfang and VIP database by computer,and then the data was extracted.Results The complete remission rate of the combined group was higher than that of the control group [33.1％ (93/281) vs.18.2％ (35/192),and the difference was statistically significant (RR =1.85,95％ CI 1.31-2.60,P ＜ 0.01).The overall response rate of the combined group was higher than that of the control group [44.0％ (124/282) vs.23.2％ (46/198)],and the difference was statistically significant (RR =1.92,95％ CI 1.44-2.56,P ＜ 0.01).However,the incidence of skin adverse reactions in the combined group was also higher than that in the control group [38.8％ (104/268) vs.3.1％ (6/192)],and the difference was statistically significant (RR =7.76,95％ CI 3.68-16.38,P ＜ 0.01).Conclusion The combination of clofarabine and cytarabine in the treatment of adult patients with MDS or AL has better clinical efficacy than single application,but it also has more serious skin adverse reactions.

Síndrome de degeneración combinada de la médula espinal y radiculopatía en dos pacientes por quimioterapia intratecal con metrotrexato y citarabina: casos clínicos / Spinal subacute combined degeneration after intrathecal chemotherapy: report of two cases

Intrathecal chemotherapy may be complicated with the development of myelopathies or toxic radiculopathies. This myeloradicular involvement, of toxic character, is unpredictable, since these patients have repeatedly received Intrathecal chemotherapy with the same drugs without apparent injury. The toxic effect should be mainly attributed to Cytarabine and not to methotrexate, since the central nervous system lacks Cytidine deaminase, the enzyme that degrades Cytarabine. We report two patients, an 18-year-old woman and a 16 years old male, who received systemic and intrathecal chemotherapy (methotrexate, cytarabine) for the treatment of an acute lymphoblastic leukemia and developed, in relation to this procedure, a spinal subacute combined degeneration. They had a proprioceptive and motor alteration of the lower extremities and neuroimaging showed selective rear and side spinal cord hyper intensity produced by central axonopathy. Two weeks later the woman developed a quadriplegia and the young man a flaccid paraplegia due to added root involvement.

The effect of the dexamethasone, cytarabine, and cisplatin (DHAP) regimen on stem cell mobilization and transplant outcomes of patients with non-Hodgkin's lymphoma who are candidates for up-front autologous stem cell transplantation

BACKGROUND/AIMS: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin’s lymphoma (NHL) is limited. METHODS: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. RESULTS: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). CONCLUSIONS: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.

Preparation of Site-specific Smart Nanocomposites for Drug Delivery and Study on Light-Controlled Cytarabine Release Performance / 中国药学杂志

OBJECTIVE: To prepare smart & site-specific drug carrier for controlled release purpose and study the bio-compatibilities and release performance.METHODS: By using high pressure thermo-heat method in autoclave, superparamagnetic core was obtained and further coated by SiO2 and MCM-41, therefore the “core-shell” structure was formed. To make the carrier “smart” and thus responsive to stimuli which was light in this research, the tunnels of the molecular sieve were grafted with gating molecules, 4,5-diazafluoren-9-one (indicated in the paper as DAFO). For bio-compatibilities testing, MTT in-vitro experiment was conducted. Cytarabine was used as test drug to preliminarily evaluate the controlled release performance of the drug carrier in vitro.RESULTS: The Fe3O4 nano-particles synthesized via high-pressure hydro-thermo procedure exhibited superparamagnetic with mean diameter of 280 nm. After SiO2 & molecular sieve coating steps and ligand grafting steps, the particles grew to 540 nm. The sub-structure of the carrier was confirmed by scanning/transmission electron microscope(SEM & TEM) and nitrogen adsorption/desorption. Our “smart” carrier was able to be guided to the sites or organs with magnetic field and more importantly it was able to unload drug molecules under 510 nm light irritation that could flip the gating-molecule. Furthermore, the drug carrier illustrated bio-compatibility and showed obvious cytotoxicity.CONCLUSION: The novel nanocomposites developed in this study can be used as targeted drug carrier.

Effect of curcumin combined with cytarabine on proliferation, autophagy and apoptosis of human acute myeloid leukemia cell line KG1a / 中国药理学通报

Aim To investigate the effect of curcumin ( CUR) combined with cytarabine( Ara-C) on the pro-liferation and apoptosis of human acute myeloid leuke-mia cell line KG1a and its relationship with autophagy. Methods The optimal combination concentration of curcumin and cytarabine was screened by MTT method and the combined effects were detected. The effects of CUR and Ara-C on the proliferation, autophagy, apop-tosis and cycle of KG1a cells were analyzed. Results Both CUR and Ara-C significantly inhibited the prolif-eration of KG1a cells ( P<0.05) , and showed a dose-and time-dependent manner. The inhibition rate of cells treated with 40 μmol·L-1CUR and 0.5 μmol· L-1 Ara-C was significantly higher than that of the other doses alone. The survival rate of cells pretreated with 3-MA was significantly decreased ( P <0.05 ) . Auto-phagic vacuoles was observed in cells with Acridine or-ange staining methods, the expression rate of the com-bination group was higher than the single group, and can be inhibited by 3-MA. The apoptosis rate of the combined group was higher than that of the single group. The apoptosis rate of the 3-MA pretreatment group was higher than that of the single group ( P <0.05). Cell numbers of the G0/G1 phase were signifi-cantly more than the S phase. The expression of caspase-3, LC3 and Beclin-1 were up-regulated while the Bcl-2 was down-regulated(P<0.05). The protein level of caspase-3 and Beclin-1 of the combination group was significantly higher than that of the single group ( P <0.05 ) , and the ratio of LC3-Ⅱ/LC3-Ⅰwas increased. The Beclin-1 expression and caspase-3 expression in 3-MA pretreatment group decreased ( P<0.05) . Conclusion Curcumin can induce autoph-agy and apoptosis of KG1a cells and increase the sensi-tivity of leukemic cells to cytarabine. Autophagy inhib-itor 3-MA can not only inhibit the autophagy but also promote apoptosis.

Effect of fludarabine combined with cytarabine on acute myeloid leukemia / 新乡医学院学报

Objective To investigate the effect of fludarabine combined with medium dose cytarabine on acute myeloid leukemia(AML).Methods A total of 55 AML patients were selected from January 2011 to January 2016 in the First People's Hospital of Xinxiang City.Among the patients,there were 16 cases of poor response after initial induction of chemotherapy (double induction group),15 cases of first induction failure(first induction failure group) and 24 cases of relapsed and refractory AML(relapsed-refractory group).All the patients were treated with fludarabine combined with medium dose cytarabine,four weeks was a course,and after treated for two courses the therapeutic effect and survival status of the patients in the three groups were compared.Results The total effective rate in the double induction group,the first induction failure group and the relapsed-refractory group was 81.3％ (13/16),66.7％ (10/15) and 33.3％ (8/24),respectively;the total effective rate in the double induction group and the first induction failure group was significantly higher than that in the relapsed-refractory group (x2 =8.839,4.127;P ＜ 0.05),but there was no significant difference in the total effective rate between the double induction group and the first induction failure group(x2 =0.860,P ＜ 0.05).The median of disease-free survival time in the double induction group,the first induction failure group and the relapsed-refractory group was 29,21 and 10 months,respectively.The disease-free survival time in the double induction group was significantly longer than that in the first induction failure group and the relapsed-refractory grouP(x2 =9.536,33.256;P ＜ 0.05),and the disease-free survival time in the first induction failure group was significantly longer than that in the relapsed-refractory group (x2 =21.077,P ＜ 0.05).The median overall survival time in the double induction group,the first induction failure group and the relapsed-refractory group was 40,29 and 12 months,respectively.The median overall survival time in the double induction group and the first induction failure group was significantly longer than that in the relapsed-refractory group (x2 =33.686,28.649;P ＜ 0.05),but there was no significant difference in the median overall survival time between the double induction group and the first induction failure group (x2 =2.417,P ＜0.05).Conclusion Fludarabine combined with medium dose cytarabine in the treatment of AML can obtain significant curative effect,and the effect in the patients with poor response after initial induction and the first induction failure is better than that in the patients with relapsed and refractory AML.

Progress of mechanism of cytarabine resistance in acute leukemia / 白血病·淋巴瘤

Cytarabine is an anti-metabolic drug with cytotoxicity, which plays an important role in the treatment of acute leukemia. Cytarabine mainly acts on S proliferation phase of tumor cells. Normally, cytosine integrates with deoxyribose to form deoxycytidine, which is one of the components of DNA. Cytarabine is a deoxycytidine analogue, which can replace the former to form DNA. Therefore, it inhibits the synthesis of cellular DNA, interferes with the proliferation of tumor cells and achieves the therapeutic purpose, due to the different structure. Different genetic backgrounds and different efficiencies of drug absorption, metabolism and elimination may result in changes in the effectiveness of the drug regimen containing cytarabine, which may affect the survival of patients with acute leukemia. The research progress of drug resistance mechanism of cytarabine in acute leukemia is reviewed and summarized in this paper.

Clinical effect observation of compound glycyrrhizin on the prevention and cure of cytarabine syndromes / 白血病·淋巴瘤

Objective To evaluate the effect of compound glycyrrhizin on the prevention and cure of cytarabine syndromes. Methods A total of 130 patients with hematological malignancies treated by moderate or high dose of cytarabine in the 303th Hospital of PLA from July 2010 to July 2016 were included. Patients were randomly divided into the control group and the experiment group by using random number table method, and each group had 65 patients. In the control group, patients were treated with cytarabine alone. In the experiment group, patients were treated with cytarabine plus compound glycyrrhizin. Skin rash and fever in patients of the two groups were also recorded. Results of blood routine tests, liver and kidney function tests were monitored during the treatment. Results Sixty-one patients in the experiment group and 63 patients in the control group were enrolled finally. In experiment group and control group, the differences in the incidence of cytarabine syndromes [8.2 % (5/61) vs. 41.3 % (26/63), χ2＝ 18.1, P < 0.001], skin rash [1.6 % (1/61) vs. 12.7 % (8/63), χ2＝16.3, P <0.001], and fever [6.6 % (4/61) vs. 36.5 % (23/63), χ2＝5.63, P <0.017] were statistically significant. There was no significant difference of the incidence of liver injury and minimum blood cell count between the two groups (P＞ 0.05). Conclusion Compound glycyrrhizin can effectively reduce the incidence of cytarabine syndromes, but the larger size and multiple center studies are needed to further verify the effect.

Venetoclax and low-dose cytarabine induced complete remission in a patient with high-risk acute myeloid leukemia: a case report / 医学前沿

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.

Protective effect of ß-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C) / Efeito protetor do ß-glucano e glutamina em lesões intestinais e imunológicas induzidas por ciratabina (Ara-C) em camundongos

Recently, glutamine and ß-glucan have been demonstrated to play an important role in modulation of the immune system and in promoting intestinal health benefits. The aim of this study was to investigate the effect of this intervention on inflammatory responses and intestinal health in mice orally pretreated with soluble Saccharomyces cerevisiae derived 1,3/1,6-ß-glucan (80mg/kg) with or without glutamine (150mg/kg) and then challenged with cytarabine (Ara-C) (15mg/kg). Improvements in villi and crypts were not observed in the ß-glucan group. The intestinal morphometry in the glutamine group showed the best results. ß-glucan in combination with glutamine presented the highest values of IL-1ß and IL-10 and lowest values for leukocytes and INF-γ. Based on these results, combined ß-glucan and glutamine pretreatment reduced intestinal inflammation and improved the immune response after Ara-C challenge.(AU)

Recentemente, glutamina e ß-glucano têm demonstrado desempenhar um papel importante na modulação do sistema imune e na promoção de benefícios para a saúde intestinal. O objetivo deste estudo foi investigar o efeito dessa intervenção sobre as respostas inflamatórias e saúde intestinal de camundongos pré- tratados por via oral com 1,3/1,6-ß-glucano (80mg/kg) derivado de Saccharomyces cerevisiae com ou sem glutamina (150mg/kg) e posteriormente desafiados com citarabina (Ara-C) (15mg/kg). Melhoras em vilosidades e criptas não foram observadas no grupo de tratamento com ß-glucano. A morfometria intestinal no grupo de tratamento com glutamina apresentou os melhores resultados. O grupo em que foi utilizado ß-glucano em combinação com glutamina apresentou os maiores valores de IL-1ß e IL -10 e valores mais baixos para os leucócitos e INF-γ. Com base nestes resultados, o pré-tratamento de ß-glucano combinado com glutamina reduziu a inflamação intestinal e melhorou a resposta imune após o desafio com Ara-C.(AU)