减低剂量去甲氧柔红霉素联合阿糖胞苷方案治疗老年急性髓细胞白血病的临床研究

目的:探讨减低剂量去甲柔红霉素联合阿糖胞苷(IA)方案治疗老年急性髓细胞白血病(AML)患者的疗效。方法:收集我院老年急性髓细胞白血病患者62例,随机分成减低剂量IA治疗组和标准剂量IA对照组,两组均实施3+7治疗方案。治疗2个疗程,比较两组不良反应和临床疗效。结果:减低剂量IA治疗组总CR率和CCR率分别为75.0%和66.7%;标准剂量IA对照组总CR率和CCR率分别为50.0%和33.3%。减低剂量IA治疗组总生存期25+月较标准剂量IA对照组生存期23+月延长。结论:对于老年急性髓细胞白血病患者,减低剂量IA治疗方案的CR率和CCR率与标准剂量IA治疗方案相比具有明显疗效优势。     

阿扎胞苷单药或联合HAG方案在骨髓增生异常综合征中的临床观察

摘要 目的：探究阿扎胞苷（Azacitidine，AZA）单药或联合HAG方案治疗骨髓增生异常综合征（Myelodysplastic syndromes，MDS）的临床疗效及安全性。方法：回顾性分析49例MDS患者的临床资料，根据治疗方法不同分为支持治疗组和含AZA组（单药或联合HAG方案），统计分析患者的临床疗效及不良反应情况。结果：支持治疗组的总有效率（Overall response rate，ORR）为30.00 %（6/20），包括0例完全缓解（Complete remission，CR），1例骨髓完全缓解（Marrow complete remission，mCR），2例部分缓解（Partial remission，PR）, 3例血液学改善（Hematological improvement，HI）。含AZA组的ORR为65.52 %，包括8例CR、2例mCR、4例PR、5例HI。其中单药组的ORR为46.67 %, 包括2例CR、1例mCR、2例PR、2例HI；联合组的ORR为85.71 %，包括6例CR、1例mCR、2例PR、3例HI。与支持治疗组相比，含AZA组的完全缓解率（CR+mCR）及ORR显著增高，差异有统计学意义（P＜0.05）。患者最常见的不良反应是III-IV级骨髓抑制（18/29）及继发感染（10/29），且随着疗程数的增加不良事件逐渐减少。含AZA组患者的中位总生存（Overall survival，OS）时间及中位无进展生存时间（Progression-free survival，PFS）时间显著延长（P＜0.05）。结论：该小系列研究的初步结果表明，与支持治疗相比，AZA单药或联合HAG方案治疗MDS有更高的治疗反应，可延长患者总生存期，患者有良好的耐受性，且联合治疗方案可能有更好的疗效。     

地西他滨联合小剂量HAG方案对急性髓系白血病患者细胞免疫功能及血清COX-2、bFGF的影响

目的:探讨地西他滨联合小剂量高三尖杉酯碱⁺阿糖胞苷⁺重组人粒细胞集落刺激因子(HAG)方案对急性髓系白血病(AML)患者细胞免疫功能及血清环氧合酶-2(COX-2)、碱性成纤维细胞生长因子(bFGF)的影响。方法:选取2016年4月~2019年4月期间山西白求恩医院收治的AML患者93例,根据随机数字表法分为对照组(n=46,HAG方案)和研究组(n=47,地西他滨联合小剂量HAG方案),比较两组患者临床疗效、细胞免疫功能、血清COX-2、bFGF水平的变化情况,记录两组治疗期间不良反应情况。结果:研究组治疗后的临床总有效率为80.85%(38/47),高于对照组的56.52%(26/46)(P<0.05)。两组治疗后CD3⁺、CD4⁺/CD8⁺、CD4⁺水平均下降,但研究组高于对照组(P<0.05);两组患者CD8⁺水平均升高,且研究组高于对照组(P<0.05)。两组治疗后血清COX-2、bFGF水平均下降,且研究组低于对照组(P<0.05)。两组不良反应发生率比较无差异(P>0.05)。结论:地西他滨联合小剂量HAG方案治疗可减轻AML患者机体免疫抑制,改善血清COX-2、bFGF水平,且用药安全性较好。     

DC-CIK过继免疫联合小剂量化疗治疗老年高危骨髓增生异常综合征的疗效分析

目的:研究树突细胞(Dendritic cells,DC)与细胞因子诱导的杀伤细胞(Cytokine-induced killers,CIK)联合化疗治疗高危骨髓增生异常综合征(MDS)患者的临床疗效及安全性。方法:应用DC-CIK联合小剂量HAG治疗23例国际预后积分系统(IPSS)评分为高危(中危Ⅱ及高危组),经过中位3(2~5)个疗程后评价疗效。结果:完全缓解者(CR)14例,部分缓解者(PR)4例,血液学改善(HI)2例,未缓解者(NR)3例,总有效率86.95%,CR率为60.87%,疗效维持中位时间为6(4.0~8.0)个月,其中11例转为急性白血病,中位转白时间12.5(7.0~18.0)个月,17例死亡,1年生存率为52.5%,2年生存率为26.09%,主要不良反应为骨髓抑制、非感染性发热。中危Ⅱ组和高危组CR率和转白时间无统计学差异(P0.05)。23名患者输注DC-CIK 2周后外周CD3+、CD4+、CD8+、CD3+CD56+淋巴细胞与输注前无明显差异,但1个月时显著高于治疗前(P0.05)。结论:DC-CIK免疫治疗与化疗联合应用于老年高危MDS具有良好的协同作用。     

PAD方案治疗75例初诊多发性骨髓瘤疗效观察

目的:PAD方案已成为目前多发性骨髓瘤(MM)治疗的一线方案,国内外就其疗效和不良反应发生均有报道,本实验旨在观察并探讨PAD方案治疗我中心初诊多发性骨髓瘤患者的疗效和不良反应,为临床工作提供参考。方法:我科75例初诊多发性骨髓瘤患者给予PAD方案4-6疗程,评估疗效及不良反应。结果:75例患者接受PAD方案化疗,四疗程后总有效率(CR+VGPR+PR)为73.3%,其中CR 5例,占6.7%,VGPR 12例,占16%,PR 38例,占50.7%;无效例数为20例,占26.7%,其中SD 17例,占22.7%,PD 3例,占4%;1年总生存率为75%,2年总生存率为62.7%。血液学不良反应有白细胞降低34例(45.3%),血小板降低10例(13.3%);非血液学不良反应有周围神经系统症状25例(33.3%),疱疹病毒感染7例(9.3%),消化系统症状15例(20%),乏力14例(18.7%),呼吸系统症状29例(38.7%),激素相关症状3例(4%)。绝大部分患者可以耐受且完成相应化疗疗程。结论:我中心PAD方案疗效令人满意,不良反应可耐受,同国内外报道的疗效反应率相近,不良反应发生率更低,是治疗多发性骨髓瘤的首选方案。     

利妥昔单抗联合CHOP化疗治疗感染乙肝病毒的非霍奇金淋巴瘤患者的安全性分析

目的:观察利妥昔单抗与CHOP化疗联合治疗感染乙肝病毒(HBV)的非霍奇金淋巴瘤(NHL)患者的有效性及安全性。方法:选取2010年6月至2013年6月35例B细胞NHL住院患者,分为两组,观察组(n=13)为感染HBV患者,接受利妥昔单抗-CHOP化疗方案;对照组(n=22)为非感染HBV的患者,单纯接受CHOP化疗方案,两组治疗4~6疗程,观察两组患者治疗的疗效及肝功能。结果:观察组完全缓解率(CR率)为76.92%,对照组CR率为40.91%(P0.05),两组差异有统计学意义。观察组肝功能损害I~Ⅱ级发生率为23.07%,对照组肝功能损害I~Ⅱ级发生率18.18%(P0.05),观察组毒副反应发生率为30.77%,对照组毒副反应发生率为22.72%(P0.05),两组在肝功能损害及毒副反应上差异无统计学意义。两组患者HBV均未再激活。结论:感染HBV的B细胞NHL患者用R-CHOP联合化疗方案治疗,以及在化疗时预防性、足疗程的抗病毒治疗,可以减少HBV再激活的发生,并且可以降低肝功损害率。     

MA诱导方案与DA诱导方案对老年急性髓系白血病患者血清炎症因子及复发率的影响

目的:探讨米托蒽醌联合阿糖胞苷(MA方案)与柔红霉素联合阿糖胞苷(DA方案)对老年急性髓系白血病(AML)患者血清炎症因子及复发率的影响。方法:选取2015年1月~2018年1月期间深圳市人民医院收治的老年AML患者129例,根据治疗方案的不同将患者分为DA组(n=64,DA方案治疗)和MA组(n=65,MA方案治疗),比较两组患者疗效、炎症因子、不良反应及复发情况。结果:MA组治疗后的临床总有效率高于DA组(P<0.05)。两组患者治疗后血清干扰素γ诱导蛋白-10(IP-10)、巨噬细胞炎症蛋白-1α(MIP-1α)及可溶性细胞间黏附分子1(sICAM-1)水平均降低,且MA组低于DA组(P<0.05)。MA组完全缓解患者中累计复发率低于DA组(P<0.05)。两组不良反应发生率比较无差异(P>0.05)。结论:与DA诱导方案相比,MA诱导方案治疗老年AML患者,可有效改善炎症因子水平,减少复发,且用药安全性较好。     

树突状细胞(DC)瘤苗治疗恶性黑色素瘤的疗效观察

目的:探讨树突状细胞瘤苗联合化疗治疗恶性黑色素瘤的疗效及不良反应。方法:采用多药联合化疗方案续贯联合树突状细胞瘤苗治疗32例恶黑患者,4周为一疗程,连续4个疗程。化学治疗组31例单纯采用联合化疗,方法及药物剂量均同生物化疗组。不良反应依据WHO化疗药物急性及亚急性不良反应分度标准判断。结果:生物化疗组32例中CR 3例,PR18例,有效率65.63%;化学治疗组31例中CR 1例,PR 11例,有效率38.71%。生物化疗组与化学治疗组疗效差异有显著性(P0.05)。两组均无治疗相关性死亡。两组的血液学毒性、消化道反应、肝功能损害、肾功能损害、神经毒性等方面差异无显著性(P0.05)。经对症处理后缓解,不影响治疗。结论:将DC细胞瘤苗免疫治疗与化学治疗有机地结合,充分发挥综合治疗的优势,有提高Ⅲ/Ⅳ期恶性黑色素瘤患者疗效的作用。     

增强剂量的CTOP方案联合放疗治疗非何杰金氏淋巴瘤的疗效观察

目的:分析增强剂量CTOP方案联合放疗治疗非何杰金氏淋巴瘤的疗效.方法:我院从2005年5月至2008年5月期间初治43例非何杰金氏淋巴瘤患者,随机分成对照组和观察组,分别采用常规剂量(THP40mg/m2)和增强剂量(THP60mg/m2)CTOP方案治疗6-8个疗程,第4-6个疗程后放疗一次,观察疗效及不良反应.结果:对照组总有效率(CR+PR)为81.82%,观察组的总有效率(CR+PR)为85.71%,疗效有所提高.两组毒副作用差异无显著性.结论:增强剂量CTOP方案结合放疗治疗非何杰金氏淋巴瘤有较好的疗效,与常规剂量CTOP方案相比毒副作用相仿.     

枳术宽中胶囊联合益生菌对老年幽门螺杆菌阳性慢性萎缩性胃炎患者的疗效

目的 探讨枳术宽中胶囊联合益生菌对老年幽门螺杆菌（H. pylori）阳性慢性萎缩性胃炎（chronic atrophic gastritis,CAG）患者的临床疗效。方法 将80例H. pylori阳性的老年慢性萎缩性胃炎患者随机分为2组,各40例。其中对照组患者给予包含雷贝拉唑、阿莫西林、克拉霉素和胶体果胶铋的标准四联疗法治疗。观察组患者将四联疗法中的胶体果胶铋替代为枳术宽中胶囊,并在此基础上加用益生菌。7天为1个疗程,全部患者治疗2个疗程。停药1个月后比较两组患者治疗前后临床症状缓解率、H. pylori根除率、不良反应发生率等情况。结果 治疗后两组患者病情均有所改善,但与对照组相比,观察组患者的症状缓解率及H. pylori根除率较高,不良反应发生率较低,差异均有统计学意义（P<0.05）。结论 枳术宽中胶囊联合益生菌可明显缓解老年CAG患者的临床症状,提高幽门螺杆菌的根除率,同时减轻患者不良反应发生率,对临床治疗CAG具有指导性意义。     

Molecular mechanism of the schedule-dependent synergistic interaction in EGFR-mutant non-small cell lung cancer cell lines treated with paclitaxel and gefitinib

The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We searched literature on CAG between 1995 and 2010 and performed a meta-analysis to determine its overall efficacy using a random-effects or fixed-effects model. Thirty five trials with a total of 1029 AML (n = 814) and MDS (n = 215) patients were included for analysis. The CR rate of AML (57.9%) was significantly higher than that of MDS (45.7%) (p < 0.01). No difference in CR was noted between the new (56.7%) and relapsed/refractory AML (60.1%) (p > 0.05). The CR rate was also significantly higher in patients with favorable (64.5%) and intermediate (69.6%) karyotypes than those with unfavorable one (29.5%) (p < 0.05). Remarkably, the CR rate of CAG was significantly higher than those of non-CAG regimens (odds ratio 2.43). CAG regimen was well tolerated, with cardiotoxicity in 2.3% and early death in 5.2% of the cases. In conclusion, CAG regimen was an effective and safe regimen for the treatment of AML, and may be more effective than non-CAG regimens. Randomized controlled trials are strongly recommended to evaluate its efficacy and safety in comparison with the current standard treatment.     

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.     

Prolonged remission maintenance in acute myeloid leukaemia.

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.     

High Doses of Daunorubicin during Induction Therapy of Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Prospective Clinical Trials

The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity.     

ATO/ATRA/Anthracycline-Chemotherapy Sequential Consolidation Achieves Long-Term Efficacy in Primary Acute Promyelocytic Leukemia

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As₂O₃, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4%±3.9% and 94.6±3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL.     

An abnormal CD34+ myeloid/CD34+ lymphoid ratio at the end of chemotherapy predicts relapse in patients with acute myeloid leukemia.

During conventional follow-up of patients with acute myeloid leukemia (AML), the emergence of cytopenias is considered to be a sign of impending relapse, and it represents an example of how leukemic hematopoiesis affects normal hemopoietic differentiation. In the present study, we have explored the possible value of the analysis of the distribution of CD34+ myeloid and CD34+ lymphoid progenitor cells in follow-up complete remission bone marrow samples from de novo AML patients as a prognostic parameter for predicting relapse. A total of 213 bone marrow samples from 36 AML patients in morphological complete remission, obtained at the end of induction, consolidation, and intensification therapy and every six months thereafter were analyzed. The normal CD34+ myeloid/CD34+ lymphoid ratio ranged between 2.4 and 8.9. In contrast, in most AML cases an abnormally high ratio (> or =10) was observed at the end of induction and consolidation therapy: 96% and 75% of cases, respectively. On the other hand, at the end of intensification, 70% of the patients displayed a normal CD34+ ratio. Patients with a myeloid/lymphoid CD34+ ratio higher than 10 at the end of intensification showed a significantly lower overall survival (median survival of 19 months versus median not reached, P = 0.05), as well as a lower disease-free survival (median of 7 months versus 30 months, P = 0.0001). Regarding sequential studies, 67% of the relapses were preceded by the re-appearance of an abnormal CD34 ratio, whereas relapse was not predicted in four patient with leukemia classified as M3 undergoing maintenance therapy. From the remaining 18 patients who are still in continuous complete remission, all except 3 cases (17%) displayed a normal CD34 myeloid/lymphoid ratio. In summary, the present study shows that the persistence at the end of chemotherapy of an abnormally high (> or =10) ratio between CD34+ myeloid and CD34+ lymphoid progenitors in the bone marrow of AML patients is associated with high risk of relapse and a shorter overall survival.     

地西他滨单药及联合半程和全程HA方案治疗骨髓增生异常综合征和急性髓系白血病的效果

目的:研究骨髓增生异常综合征和急性髓系白血病治疗中地西他滨单药及联合半程和全程HA方案的效果。方法:采用回顾性分析方法,选择2016年6月至2019年6月入院的80例骨髓增生异常综合征与急性髓系白血病患者,参考不同治疗方式分为研究组(40例)与对照组(40例),研究组选用地西他滨联合全程HA方案治疗,对照组选用地西他滨联合半程HA方案治疗;比较两组治疗后血小板、中性粒细胞减少持续时间、缓解率、总反应率及毒副反应发生率。结果:研究组治疗后血小板、中性粒细胞减少持续时间与缓解率、总反应率及毒副反应发生率依次为(10.18±0.98)d、(11.57±1.34)d、70.00%、82.50%、7.50%,对照组治疗后血小板、中性粒细胞减少持续时间与缓解率、总反应率及毒副反应发生率依次为(16.45±1.46)d、(18.03±1.92)d、30.00%、60.00%、25.00%。研究组较对照组治疗后血小板、中性粒细胞减少持续时间更短,缓解率及总反应率更高,毒副反应发生率更低(P<0.05)。结论:地西他滨联合全程HA方案治疗骨髓增生异常综合征和急性髓系白血病的效果优于地西他滨联合半程HA方案,且毒副反应少。     

Selenium and Glutathione Peroxidase Status in Adult Egyptian Patients with Acute Myeloid Leukemia

This study was undertaken to evaluate selenium (Se) and glutathione peroxidase (GPX) status in patients with newly diagnosed acute myeloid leukemia (AML) before and after induction therapy. Twenty-five patients with newly diagnosed AML and 15 healthy age- and sex-matched control subjects were included in this study. Serum Se level by the graphite furnace atomic absorption spectrometric technique and GPX activity by an adaptation of Beutler method was performed for the patients before and after receiving the induction therapy. Serum Se level was significantly lower in patients with AML versus control subjects (63.1?±?8.8 versus 77?±?8.8 µg/L before therapy with a P value <0.01 and 69?±?6.8 versus 77?±?8.8 µg/L after therapy with a P value <0.01).GPX activity was significantly lower in patients with AML versus control subjects (1.6?±?0.4 versus 3.4?±?0.7 µ/g protein pretreatment with a P value <0.01and 1.9?±?0.6 versus 3.4?±?0.7 µ/g protein post induction treatment with P value <0.01).Se level and GPX activity significantly increased in AML patients after treatment. Patients who accomplished complete remission after induction harbored significantly higher Se levels than resistant patients before and after treatment. There was no significant correlation between serum Se level and GPX activity. Decreased Se level and reduced GPX activity in AML patients support the association of carcinogenesis and subnormal Se states.