抗淋巴细胞免疫球蛋白(猪)联合环孢素治疗重型再生障碍性贫血

Objective To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG)plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). Methods Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA)were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. Results The median age was 28 (13 -64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0. 178 × 109/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 -380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5% ,0, 100%, respectively, P ＜ 0. 05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness(16. 7%), impaired liver function(60.4%)and hemorrhage(2.1%). No treatment-related mortality was found. Conclusion P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.     

抗淋巴细胞免疫球蛋白(猪)联合环孢素治疗重型再生障碍性贫血

目的 评价国产猪抗淋巴细胞免疫球蛋白(ALG)+环孢素(CsA)治疗重型再生障碍性贫血(SAA)的疗效.方法 回顾性分析1999年至2009年48例(男31例,女17例)联合应用猪ALG和CsA治疗的SAA患者资料,观察治疗后的近期及长期疗效、并发症及转归,并根据患者的年龄、疾病严重程度、发病距使用ALG的时间及治疗前有无感染进行分层分析.结果 48例患者中位年龄为28(13～64)岁.从诊断到治疗的中位时间为45 d.发病时患者中性粒细胞中位数为0.178×109/L.48例患者中26例(54.2%)基本治愈,14例(29.2%)缓解,总有效率为83.3%,恢复时间为90(23～380)d.治疗后短期死亡5例(10.4%),主要死亡原因为感染(真菌为主).1例患者2年后复发,无进展为克隆性疾病的病例.1.5年的生存率为87.5%.极重型再生障碍性贫血(vSAA)患者总有效率、早期死亡率及总生存率均较SAA患者差(64.7%、29.4%、51.8%vs93.5%、0、100%,P值均＜0.01).不同年龄、性别、诊断至治疗的时间及治疗前是否合并感染组的治疗有效率差异无统计学意义(P值均＞0.05).主要不良反应为发热、皮疹(52.1%)、血清病(16.7%)、肝功能损伤(60.4%)、出血(2.1%),无治疗相关死亡率.结论 采用国产猪ALG联合CsA对初治SAA患者有较理想的疗效,且较传统的马或兔ATG,猪ALG的治疗费用更经济.vSAA者预后不佳.

Abstract：

Objective To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG)plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). Methods Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA)were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. Results The median age was 28 (13 -64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0. 178 × 109/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 -380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5% ,0, 100%, respectively, P ＜ 0. 05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness(16. 7%), impaired liver function(60.4%)and hemorrhage(2.1%). No treatment-related mortality was found. Conclusion P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.     

一线应用兔源抗胸腺细胞球蛋白联合环孢素治疗成人重型再生障碍性贫血疗效分析

目的 研究成人重型再生障碍性贫血(SAA)一线应用兔源抗胸腺细胞球蛋白(r-ATG)联合环孢素(CsA)免疫抑制治疗(IST)的疗效及不良反应.方法 回顾性分析我院2003年至2008年贫血诊疗中心收治的79例成人初始SAA或极重型再生障碍性贫血(VSAA)患者临床资料,评价IST疗效及分析相关因素.结果 6例患者早期死亡,73例患者可进行疗效评价,60例(82.2%)获得治疗反应,获得治疗反应的患者脱离输注血制品的中位时间为60 d.32例SAA患者均获治疗反应,治疗反应率(100%)高于41例VSAA组患者的68.3%(P=0.001).获得G-CSF治疗反应的患者较无反应者IST疗效明显增高(100%对67.5%,P=0.001).共61例(77.2%)患者出现血清病反应.获得治疗反应的患者3例复发,2例发生克隆性血液学异常.应用该方法治疗,患者预计3年总生存率为88.9%.结论 一线应用r-ATG联合CsA治疗成人SAA疗效高,不良反应轻微.

Abstract：

Objective To analyze the efficacy and side-effects of combination of rabbit antithymocyte globulin (ATG) and cyclosporine A(CsA) as the first-line immunosuppressive therapy (IST) for adult severe aplastic anemia ( SAA ) patients. Methods Adult SAA or very severe aplastic anemia ( VSAA ) patients treated with rabbit ATG + CsA as first line therapy in our hospital from 2003 to 2008 were retrospectively analysed and the therapeutic response relevant factors were analysed. Results Seventy-nine patients were enrolled. Of all these patients, 6 died within 3 months after IST. The overall response rate was 82.2% and the median time to transfusion independent was 60 days. The therapeutic response rate in 32 SAA patients ( 100% ) was significantly higher than that in 41 VSAA cases (68.3%) ( P = 0.001 ). Patients with neutrophil response to G-CSF treatment had a higher IST response rate than those without response to G-CSF ( 100% vs 67.5%, P=0.001 ). Sixty-one patients (77.2%) occurred serum sickness reaction. Three patients relapsed and two developed clonal hematological abnormdities after IST. The 3-year overall survival for all the patients was 88.9%. Conclusions Rabbit ATG in combination with CsA as first-line IST for adult SAA can lead to excellent treatment outcomes with minor adverse effects.     

Surgery for colorectal cancer in Greece

Objective The aim of this study is to analyse our experience and assess the outcome of surgery for colorectal cancer with curative intent in Greece.Methods During the last 10 years,550 patients were treated for colorectal cancer with curative intent.291(52.9%) of the patients suffered from colonic cancer while 259(47.1%) were operated for rectal cancer.Tumour site,Astler?Coller and TNM classifications and surgical procedures were recorded.Total mortality,morbidity and 5?year survival were evaluated.Results Morbidity rate was 12.0% and mortality rate was 0.68% for colonic cancer surgery,whereas the overall five year survival rate was 77.9%.Morbidity rate was 16.9% and mortality rate was of 0.38% for rectal cancer patients.The overall five year survival rate was 79.6%.Conclusion Morbidity,mortality rate and 5?year survival after colorectal surgery in our department in Greece are comparable to those published in the international literature.     

造血干细胞移植治疗重型再生障碍性贫血

Objective To evaluate the therapeutic effects of allogeneic hematopoietic stem cell transplantat (allo-HSCT) for severe aplastic anemia (SAA). Methods Four patients of SAA underwent allo-HSCT at the bonemarrow transplant unit in our hospital from March 2003 to May 2009. Stem cell source was an HLA (human leukocyte antigen) matched related donor (MRD) in 3, HLA 1 (B) mismatched related donor in 1 patient A retrospective analysis was performed on interval from diagnosis to transplant,HSCT manners,conditioning regimens, hematopoiesis reconstitution, effectiveness and complication. Results The interval from diagnosis to transplant was 70 (19 - 180) days. Three patients (MRD) underwent BM + PBSCT, one was undergone BM + PBSC + CBSCT. Conditioning regimens of all patients were CY/ATG. Hematopoiesis reconstitution was achieved in 4 patients (100%). The median time of neutrophils which reached 0. 5 x 109/L and platelets reached 20 × 109/L were 14. 5 (9-28) and 16(9 -28) days. Two cases developed grade Ⅰ acute graft-versus-host diseaes (aGVHD), chronic local GVHD occurred in one patient. Four patients are alive with a median time of 40. 6(2 -63) months at the end of the following-up. Conclusions Allo-HSCT are an efficient and safe therapy for the patient with SAA,not only for patients with HLA matched related donor,but also for those only HLA mismatched related donor available.     

造血干细胞移植治疗重型再生障碍性贫血

Objective To evaluate the therapeutic effects of allogeneic hematopoietic stem cell transplantat (allo-HSCT) for severe aplastic anemia (SAA). Methods Four patients of SAA underwent allo-HSCT at the bonemarrow transplant unit in our hospital from March 2003 to May 2009. Stem cell source was an HLA (human leukocyte antigen) matched related donor (MRD) in 3, HLA 1 (B) mismatched related donor in 1 patient A retrospective analysis was performed on interval from diagnosis to transplant,HSCT manners,conditioning regimens, hematopoiesis reconstitution, effectiveness and complication. Results The interval from diagnosis to transplant was 70 (19 - 180) days. Three patients (MRD) underwent BM + PBSCT, one was undergone BM + PBSC + CBSCT. Conditioning regimens of all patients were CY/ATG. Hematopoiesis reconstitution was achieved in 4 patients (100%). The median time of neutrophils which reached 0. 5 x 109/L and platelets reached 20 × 109/L were 14. 5 (9-28) and 16(9 -28) days. Two cases developed grade Ⅰ acute graft-versus-host diseaes (aGVHD), chronic local GVHD occurred in one patient. Four patients are alive with a median time of 40. 6(2 -63) months at the end of the following-up. Conclusions Allo-HSCT are an efficient and safe therapy for the patient with SAA,not only for patients with HLA matched related donor,but also for those only HLA mismatched related donor available.     

Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation: Results from a retrospective study on 38 Chinese patients

BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.     

进展期结直肠癌动脉灌注新辅助化疗临床疗效观察

Objective To evaluate the curative effect of neoadjuvant chemotherapy via arterial infusion on advanced colorectal carcinoma. Methods One hundred and twenty-eight advanced colorectal carcinoma patients in stage Ⅱ B or Ⅲ were randomly divided into 2 groups. Sixty-eight cases received preoperative arterial infusion chemotherapy( the treatment group),and chemotherapy regimen consist of Oxaliplatin(L-OHP) 130 mg/m2, Hydroxycamptothecin (HCPT) 20 mg/m2 and Dexifluridine (FUDR)600 mg/m2. Femoral arterial infusion chemotherapy administrated 8 ～ 14 days preoperative. Sixty cases received surgery directly(the control group). The adverse reaction and histology effect after arterial infusion chemotherapy were observed, and resection rate,complications,pathology stage,together with long term survival were compared. Results Adverse reaction were mostly grade Ⅰ -Ⅱ gastrointestinal discomfort and bone marrow depression with arterial infusion chemotherapy. Resection rate was 97. 1% (66/68) ,and 64 cases(96. 9%) underwent raclical (R0) resection in the treatment group, which were higher than those in the the control group(73. 3%(44/60) and 79. 5%,respectively) (x2 = 14. 848,8. 906, Ps ＜ 0. 05). Histology effect of the treatment group was 72. 7%, and the pathology stage downstaged compared to preopeartion. Percent of patients in stage Ⅱ in the treatment group was higher than that in the control group( P ＜ 0. 05). The median survival time of test group was 53. 0 months, 1- ,3-,and 5-year survival rates were 95.3%,85.9% and 44.6%, respectively. In the control group, the median survival time was 42.0 months, 1-, 3-, and 5-year survival rates were 92.6%, 75.9% and 22.0%,respectively. There was significant difference in 5-year survival rate(x2 = 6. 385, P ＜ 0. 05). No difference in postoperative complications between two groups(P ＞ 0. 05). Conclusion The neoadjuvant chemotherapy via arterial infusion is of great significance on downstnging the pathology of advanced colorectal carcinoma, raising the excision rate, especially radical resection, and long term survival rate.     

危重病严重脓毒症/脓毒性休克患者早期规范化液体复苏治疗——多中心、前瞻性、随机、对照研究

Objective To investigate the effect of early goal-directed therapy (EGDT) on treatment of critical patients with severe sepsis/septic shock.Methods A multi-center, prospective, randomized,controlled study was deployed.Totally 314 critical patients, from eight comprehensive hospitals in Zhejiang Province admitted during January, 2005 to January, 2008, suffering from severe sepsis/septic shock were randomized into conventional treatment group (n=151) and EGDT group (n = 163), the patients of the former underwent fluid resuscitation guided by central venous pressure (CVP), systolic blood pressure (SBP) or mean artery pressure (MAP) and urinary output (UO), and the latter guided by CVP, SBP orMAP and UO plus central venous oxygen saturation (ScvO2).The patients were treated with fluid, blood transfusions and cardiac stimulants in a period of 6 hours after enrollment to reach the goal.The difference of 28-day survival rate and intensive care unit (ICU) mortality (primary end points), the length of ICU stay,the duration of mechanical ventilation, duration of antibiotics treatment, incidence of newly occurredinfection, and severity scores (secondary end points) were compared between two groups.Results Finally,a total of 303 patients were eligible to enter this study, with 157 patients in EGDT group and 146 patients in conventional treatment group.In comparison with conventional treatment group, the 28-day survival rate of EGDT group was increased by 17.7% (75.2% vs.57.5%, P=0.001) and the ICU mortality of EGDT group was decreased by 15.7% (35.0% vs.50.7%, P=0.035), the acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score (14.4±8.5 vs.18.0±7.1, P=0.043), multiple organ dysfunction syndrome (MODS) score (5.8±3.1 vs.8.9±3.7, P=0.014) and sepsis-related organ failure assessment (SOFA) score (5.6 ± 2.9 vs.10.4 ± 3.7, P = 0.001) were significantly decreased in EGDT group.Meanwhile, a significant shortening of duration of using antibiotics was also found [(13.4±10.0) days vs.(19.7 ± 13.5) days, P = 0.004], with a lowering of incidence of occurrence of new infection (37.6% vs.53.4%, P=0.014).There were no differences in other parameters for secondary end points.Conclusion EGDT improves 28-day survival rate and clinical scores, and it shows beneficial effects on outcome of critical patients with severe sepsis/septic shock.     

Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value 0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.