DC 与CIK细胞治疗难治复发急性髓细胞白血病的近期临床观察

目的：评估自体DC与CIK 细胞治疗难治复发急性髓细胞白血病的近期疗效与安全性。方法：给予20 例难治复发急性髓细 胞白血病患者树突状细胞(DC)与细胞因子诱导的杀伤细胞(CIK)治疗,20 例难治复发的应用同样化疗方案的急性髓细胞白血病 患者做为对照组;治疗后4 周观察两组患者临床疗效和生存质量(KPS)评分,DC 与CIK 细胞治疗前和治疗后1 周检测T细胞亚 群(CD3+、CD3+CD4+、CD3+CD8+、CD3+CD56+)和细胞因子(IL-12、IL-2、IL-7、IFN-酌及TNF-琢)水平的变化。结果：①DC 与CIK 细胞 治疗组有效率和KPS评分明显高于对照组(P<0.05),所有患者的不良反应轻微,均可耐受。②DC 与CIK 细胞治疗后1 周,患者T 细胞亚群百分比和细胞因子含量较治疗前均明显升高,其中CD3+、CD3+CD56+及IL-12、IL-7 明显升高(P<0.05)。结论：DC与CIK 细胞免疫治疗难治复发急性髓细胞白血病安全有效。     

DC与CIK细胞治疗难治复发急性髓细胞白血病的近期临床观察

目的：评估自体DC与CIK细胞治疗难治复发急性髓细胞白血病的近期疗效与安全性。方法：给予20例难治复发急性髓细胞白血病患者树突状细胞（DC）与细胞因子诱导的杀伤细胞（CIK）治疗,20例难治复发的应用同样化疗方案的急性髓细胞白血病患者做为对照组;治疗后4周观察两组患者临床疗效和生存质量（KVS）评分,DC与CIK细胞治疗前和治疗后1周检测T细胞亚群（CD3＋、CD3＋CD4＋、CD3＋CD8＋、CD3＋CD56＋）和细胞因子（IL-12、IL-2、IL-7、IFN-γ及TNF—α）水平的变化。结果：（1）DC与CIK细胞治疗组有效率和KPS评分明显高于对照组（P〈0．05）,所有患者的不良反应轻微,均可耐受。（2）DC与CIK细胞治疗后1周,患者T细胞亚群百分比和细胞因子含量较治疗前均明显升高,其中CD3＋、CD3＋CD56＋及IL-12、IL-7明显升高（P〈0．05）。结论：DC与CIK细胞免疫治疗难治复发急性髓细胞白血病安全有效。     

AVASTIN联合泰索帝治疗HER-2阳性晚期乳腺癌2例及文献回顾

目的:观察AVASTIN联合泰索帝治疗Her-2阳性乳腺癌的疗效及不良反应;方法:2例Her-2阳性的复发转移性乳腺癌患者均接受AVASTIN联合泰索帝方案治疗,AVASTIN 15mg/kg静滴,第1天;同时给予泰索帝75mg/m2,第1天;21天1周期.每周期评价疗效同时记录不良事件.结果:2例患者疗效评价分别为SD(好转)和PR.2例患者均发生白细胞及粒细胞减少4级,脱发、疼痛2级,厌食、腹泻、鼻衄1级,未观察到高血压、静脉血栓、蛋白尿.结论:AVASTIN联合泰索帝可用于治疗Her-2阳性的复发转移性乳腺癌患者,其不良反应能够耐受.     

用链亲和素-胶体金原位杂交方法检测白血病多药耐药基因的表达

用链亲和素-胶体金原位杂交(ISH-SAG)方法检测了50例急性白血病和2例慢性粒细胞白血病急变患者骨髓单个核细胞多药耐药基因(MDR1)的表达。全部52例患者中24例(46.2％)MDR1呈阳性表达。其中初治组阳性35.7％(10/28),复发难治组66.7％(12/18),两     

G-CSF诱导移植物抗白血病效应治疗异基因造血干细胞移植后复发白血病的研究

目的观察应用G-CSF诱导移植物抗白血病效应治疗异基因造血干细胞移植后复发白血病的疗效。方法对2011年7月至2013年2月该科异基因造血干细胞移植后40例复发的白血病患者,进行输注粒细胞集落刺激因子动员后供者外周血单个核细胞治疗。其中-CR3髓系有4例,细胞混合有6例,-CR2淋巴细胞有10例,-CR2髓系有16例,髓系加速期慢性有4例。在异基因造血干细胞移植后,半年内,40例患者均复发,予G-CSF动员后,供者外周血单个核细胞输注,每次输注细胞量逐级增加,每次输注间隔4周。结果 24例患者再次缓解完全,未缓解的16例。患者输注后,6例发生急性移植物抗宿主病Ⅰ~Ⅱ度,24例发生慢性移植物抗宿主病,5例未发生并发症。结论 G-CSF诱导移植物抗白血病效应治疗后,白血病复发有较好的疗效,不良反应小,值得临床推广。     

Hyper-CVAD/MA治疗复发或难治性弥漫大B 细胞淋巴瘤的临床研究

目的:探讨Hyper-CVAD/MA方案治疗复发或难治弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的疗效及安全性。方法:观察26例经系统化疗后复发或难治的DLBCL患者接受Hyper-CVAD/MA方案化疗,21-28天为1周期,连续2个周期评价疗效及安全性,分析生存情况。结果:全组26例患者中,总有效率为46.15%,其中完全缓解(complete remission,CR)3例(11.54%),部分缓解(partial remission,PR)9例(34.61%),全组患者中位生存时间为10(2-25)个月,1年和2年总生存率分别为28.57%、14.29%。不良反应主要表现为III-IV度骨髓抑制及继发的肺部感染,其他包括胃肠道反应、口腔炎、肝功能异常等。结论:Hyper-CVAD/MA治疗复发难治DLBCL有一定的疗效,且患者可耐受,可作为二线方案的一个选择。     

利奈唑胺治疗高龄重症肺炎致血小板减少16例临床分析

目的:分析利奈唑胺治疗高龄重症肺炎患者致血小板减少的特点,为高龄患者合理用药提供参考.方法:回顾性分析16例高龄重症肺炎利奈唑胺治疗的临床资料,分析其临床疗效及危险因素,总结其不良反应的发生情况.结果:男14例,女2例,年龄81-99岁,平均91.2± 1.4岁.有13例(81.25％)发生血小板减少,多在用药3～7天发生,停药后恢复时间5～10天.结论:利奈唑胺治疗80岁以上重症肺炎患者血小板下降发生机率高,建议应用利奈唑胺治疗过程中密切监测血象,一旦发现血小板减少,及时停药,以免严重不良反应发生.     

草酸铂联合FL三周方案二线治疗晚期肠癌25例疗效分析

目的评价草酸铂（L-OHP）联合氟脲嘧啶（5-FU）、甲酰四氢叶酸钙（CF）二线治疗晚期复发大肠癌的疗效和不良反应。方法L-OHP 130 mg/m^2,静脉滴入,2 h,d1;CF 100 mg/m^2,5-FU前2小时静脉滴入,d1-d5;5-FU 500 mg/m^2,静脉滴入,6-8 h,d1-d5,21 d为1个周期。结果全组CR 1例,PR 3例,SD 17例,PD 4例,总有效率为16%,疾病控制率为84%。主要不良反应为中性粒细胞减少、消化道反应及外周神经毒性。结论L-OHP联合5-FU、CF方案（OFL）二线治疗晚期复发大肠癌安全、有效,毒性反应可耐受。     

硼替佐米皮下注射的护理体会

目的:探讨治疗多发性骨髓瘤硼替佐米采用静脉注射浓度进行皮下注射(1mg/ml)患者的观察要点及护理;方法:注射用硼替佐米3.5mg/支加生理盐水3.5ml溶解,用法为1.0-1.3 mg/m2,于治疗第1、4、8、11天时皮下注射,两次给药之间至少间歇72小时,12天为一疗程;结果:30例患者在化疗期间均未发生严重局部皮肤反应,原发疾病无进展,周围神经病变相比静脉注射后明显减轻。结论:硼替佐米治疗多发性骨髓瘤疗效确切,采取静脉注射浓度进行皮下注射1mg/ml皮下注射,患者对局部不良反应是可以耐受的,并减少了毒副作用。     

培美曲塞单药或联合铂类治疗晚期复治非小细胞肺癌54例临床观察

目的:培美曲塞是一种多靶点抗叶酸化疗药,目前已成为晚期非小细胞肺癌二线治疗的标准药物.本研究回顾分析培美曲塞单药或联合铂类治疗晚期复治非小细胞肺癌的疗效及不良反应.方法:对既往至少接受过1个标准含铂方案化疗的54例晚期非小细胞肺癌怠者,分为单药治疗组21例,联合铂类治疗组33例.单药治疗组给予培美曲塞单药治疗,培美曲塞500mg/m2,第1天,21天为1个周期;联合铂类治疗组给予培美曲塞联合顺铂或卡铂,培美曲塞500mg/m2,第1天,顺铂75 mg/m2或卡铂AUC=5,第1天,21天为1个周期.评价疗效及不良反应.结果:54例患者均可评价疗效.单药治疗组PR 1例,RR4.8%,SD10例,疾病控制率(DCR)52.4%,PD10例(47.6%).中位无进展生存期3.8个月;联合治疗组PR4例,RR12.1%,SD20例,疾病控制率(DCR)72.7%,PD9例(27.3%).中位无进展生存期4.8个月.与药物相关的不良反应主要为:Ⅰ/Ⅱ度骨髓抑制、胃肠道反应.结论:培美曲塞或与铂类联合治疗晚期复治非小细胞肺癌有效,不良反应轻微、可耐受.     

Adoptive transfer of T cells transduced with a chimeric antigen receptor to treat relapsed or refractory acute leukemia: efficacy and feasibility of immunotherapy approaches

Treatment outcomes of acute leukemia(AL) have not improved over the past several decades and relapse rates remain high despite the availability of aggressive therapies. Conventional relapsed leukemia treatment includes second allogeneic hematopoietic stem cell transplantation(allo-HSCT) and donor lymphocyte infusion(DLI), which in most cases mediate, at best, a modest graft-versus-leukemia effect, although their clinical efficacy is still limited. Although allo-HSCT following myeloablative conditioning is a curative treatment option for younger patients with acute myeloid leukemia(AML) in a first complete remission(CR), allo-HSCT as a clinical treatment is usually limited because of treatment-related toxicity. The overall DLI remission rate is only 15%–42% and 2-year overall survival(OS) is approximately 15%–20%, with a high(40%–60%) incidence of DLI-related graft-versus-host disease(GVHD). Therefore, development of new, targeted treatment strategies for relapsed and refractory AL patients is ongoing. Adoptive transfer of T cells with genetically engineered chimeric antigen receptors(CARs) is an encouraging approach for treating hematological malignancies. These T cells are capable of selectively recognizing tumor-associated antigens and may overcome many limitations of conventional therapies, inducing remission in patients with chemotherapy-refractory or relapsed AL. In this review, we aimed to highlight the current understanding of this promising treatment modality, discussing its adverse effects and efficacy.     

Detection of minimal residual disease (MRD) after bone marrow transplantation (BMT) by multi-parameter flow cytometry (MPFC)

Multi-parameter flow cytometry (MPFC) was used to detect minimal residual disease (MRD) following bone marrow transplantation (BMT) in 21 patients. Bone marrow (BM) was analyzed pre-transplant and 3–4 months post-BMT while the patients were in clinical and morphological remission. MRD was detected by identifying cells with aberrant antigen expression and/or leukemia-associated phenotype (LAP) using MPFC. Prior to BMT, 8 out of 21 patients exhibited normal antigen expression based on normal BM samples while 13 BM aspirates had abnormal MPFC. Pre-BMT MPFC was abnormal in all 10 patients who were not in complete remission (CR) (>5% blasts in BM) as well as 3 patients acute lymphoblastic leukemia (ALL) who were in CR. In BM from ALL patients, an abnormal uniform B cell population was observed however antigen expression patterns varied greatly between patients. BM from acute myeloblastic leukemia (AML) patients showed an abnormal distribution of CD34+ cells. In addition, a correlation was observed between pre-BMT cytogenetics and MPFC. Only 2 out of 8 (25%) patients with normal MPFC pre-autologous bone marrow transplantation (ABMT) relapsed (AML), while 6 out of 13 (46%) patients with abnormal pre-BMT MPFC relapsed including 2 out of 3 patients who were transplanted in clinical CR. Pre-BMT MPFC may thus be an effective tool for detection of MRD by detection of a pre-transplant MPFC abnormality.     

Deregulation of Mitochondrial ATPsyn-β in Acute Myeloid Leukemia Cells and with Increased Drug Resistance

The mechanisms underlying the development of multidrug resistance in acute myeloid leukemia are not fully understood. Here we analyzed the expressions of mitochondrial ATPsyn-β in adriamycin-resistant cell line HL-60/ADM and its parental cell line HL-60. Meanwhile we compared the differences of mitochondrial ATPsyn-β expression and ATP synthase activity in 110 acute myeloid leukemia (AML, non-M3) patients between relapsed/refractory and those in remission. Our results showed that down-regulation of ATPsyn-β expression by siRNA in HL-60 cells increased cell viability and apoptotic resistance to adriamycin, while up-regulation of mitochondrial ATPsyn-β in HL-60/ADM cells enhanced cell sensitivity to adriamycin and promoted apoptosis. Mitochondrial ATPsyn-β expression and ATP synthase activity in relapsed/refractory acute myeloid leukemia patients were downregulated. This downregulated ATPsyn-β expression exhibited a positive correlation with the response to adriamycin of primary cells. A lower expression of ATPsyn-β in newly diagnosed or relapsed/refractory patients was associated with a shorter first remission duration or overall survival. Our findings show mitochondrial ATPsyn-β plays an important role in the mechanism of multidrug resistance in AML thus may present both a new marker for prognosis assessment and a new target for reversing drug resistance.     

Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia： potential contribution to AML proqression

Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair （MMR） function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease Datho8enesis.     

Day-6 bone marrow aspirate for the prediction of response to remission induction therapy for acute myelogenous leukaemia

Seventy-two adults were treated for acute myelogenous leukaemia (AML). Forty-two had previously untreated AML and 30 had AML after a preleukaemic phase, refractory AML or relapsed AML. The previously untreated patients received a 7-day course of cytosine arabinoside (100 or 200 mg/m2 daily), daunorubicin and vincristine while the remaining patients received a 7-day course of cytosine-arabinoside (1 g/m2 q 12h for 6 days) and amsacrine (on day 7). The percentage of malignant cells and the reduction in the percentage of malignant cells were determined by means of bone marrow aspirates taken on day 6 of the chemotherapy course and at the time of diagnosis. Both variables correlated significantly with the ultimate treatment outcome; the reduction in the percentage of malignant cells correlated even more significantly than the absolute percentage malignant cells in the day-6 bone marrow. By means of multiple regression analysis it became possible to calculate the probability of achieving complete remission for the individual patient; this is given by the equation: probability = 1.9-0.009X (% malignant cell reduction). In addition, the mean percentage of malignant cells in the day-6 bone marrow was significantly higher for patients who failed to achieve than those who entered complete remission. Eighty-six per cent of the patients with less than 20% malignant cells on day 6 entered remission, while 75% of the patients with more than 21% malignant cells failed to achieve complete remission (p less than 0.001). Although all of these calculations support the predictive value of the day-6 bone marrow aspirate, the 95% confidence intervals are too large to allow reliable and safe predictions; therefore more patients must be studied to demonstrate the reliability of this test.     

Spastic paralysis of the lower extremities as the first symptom of acute myeloblastic leukemia]

A case of acute myeloblastic leukemia (AML) with spastic paralysis of the lower extremities caused by a tumor of the spinal cord as the first symptoms of the disease is presented. The tumor consisted of leukaemic cells. A diagnosis of AML type M2, according to FAB classification, was established. A complete remission was achieved after 2 courses of chemotherapy. Patient started to walk after intensive rehabilitation. After 14 months of complete remission, recurrence was observed despite an intensified therapy.     

A test with dexamethasone in acute leukemia.

A simple test with dexamethasone (DMS) in acute leukemia (AL) is described. In peripheral blood, blast cell count is determined before 8 mg DMS are given intravenously, and 2, 4 and 6 hours afterwards. The result is expressed as the lowest blast cell count after DMS in percentage of the initial value. This test was performed on 51 adult patients with AL. The results were correlated with the morphological and cytochemical classification. Only patients with clearly classified AL were evaluated. A statistically significant difference in blast cell response between acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) was observed. In 12 out of 16 cases of ALL, but in only 1 out of 19 cases of AML, the blast cell count decreased to 50 percent or less of the initial value. The results of the test were further correlated with the results of treatment. In 11 out of 12 patients with ALL, who showed a response to DMS, glucocorticoids were included in the treatment regimen. A complete remission was obtained in 7 out of 10 patients who were treated for the first time. In the remaining 4 patients with a poor response to DMS, a complete remission after the first treatment was obtained in only one case. The number of patients examined is to small for final conclusions on the value of this test for a discrimination between glucocorticoid-responsive and non-responsive cases of AL. Nevertheless, these preliminary results indicate that further trials seem to be warranted.     

Impact of prophylactic/preemptive donor lymphocyte infusion and intensified conditioning for relapsed/refractory leukemia: a real-world study

Prophylactic/preemptive donor lymphocyte infusion(p/pDLI) and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL), but real-world data remain scarce. We conducted a multicenter, population-based analysis of 932 consecutive patients. The three-year leukemia-free survival(LFS) rates were 56% for patients receiving both p/pDLI and intensified myeloablative conditioning(MAC)(intenseMAC) and 30% for those who received neither therapy per landmark analysis. Multivariable analyses were run separately for acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL), and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality. IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL, while there was no impact of intenseMAC observed in AML. p/pDLI achieved superior outcomes in both matched-sibling donor(MSD) and haploidentical donor transplantation, while intenseMAC only influenced MSD outcomes. Data suggest that RRAL patients receiving "total therapy" by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS, with p/pDLI being safer with a more extensive impact relative to intenseMAC. Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.     

缓解与未缓解髓系白血病干细胞表面抗原CD34~+CD123~+表达差异研究

目的:探索缓解与未缓解急性髓系白血病干细胞表面抗原表达差异,为判定化疗疗效及其预后提供依据。方法:按照急性白血病诊断标准,根据患者入院时骨髓白血病细胞数量多少分成临床缓解与未缓解两组,以流式细胞仪分别检测骨髓中白血病干细胞表面相关抗原表达情况,比较二者之间差异。其中经标准化疗方案治疗结束后,通过复查骨髓象判定疗效并比较化疗前后白血病干细胞表面相关抗原表达变化。结果:与缓解的急性髓系白血病患者骨髓白血病干细胞相关抗原表达值相比,未缓解的患者骨髓白血病干细胞表面相关抗原表达明显升高,差异具有统计学意义(P0.05,0.001);未缓解的患者经标准方案化疗后骨髓虽然已经获得完全缓解,但依然具有白血病干细胞表面抗原高表达,提示这部分患者依然有复发的可能性。结论:急性髓系白血病患者的白血病干细胞相关抗原表达值升高是急性白血病复发难治的根源之一。     

Secondary leukemia after severe aplastic anemia

We describe a patient with acute myeloid leukemia (AML) occurring 5 years after successful treatment of severe aplastic anemia (SAA) with antilymphocyte globulin (ALG). Four years after ALG, SAA had relapsed. A second remission of SAA was achieved, but was followed by transformation of the myelodysplastic syndrome into overt AML. After 2 courses of high-dose cytosine arabinoside and VP-16 complete remission occurred. This case shows that chemotherapy of secondary leukemia after SAA is feasible, and that ex-aplastic bone marrow is capable of complete recovery from chemotherapy-induced aplasia. Morphological anomalies of bone marrow noticed early during remission of SAA might predict a late transformation in leukemia.