HDA方案治疗急性非淋巴细胞白血病临床研究

１９８５年～１９９３年收治急性非淋巴细胞白血病（ＡＮＬＬ）２１８例，用ＨＤＡ方案治疗７２例，ＣＲ率为７６．３８％、ＨＡ方案治疗７８例，ＣＲ率４４．８７％、ＤＡ方案治疗６８例，ＣＲ率４８．８５％，ＨＤＡ组与ＨＡ、ＤＡ组疗效差异显著（Ｐ＜０．００５），ＣＲ后必须坚持长期多疗程的强化治疗才能延长生存期、提高治愈率。     

骨髓移植后肝功能损害的病因分析及治疗探讨

目的探讨骨髓移植（ＢＭＴ）患者肝功能损害的病因及其防治措施。方法对３６例ＢＭＴ患者分别动态检测其肝功能及肝炎病毒、ＣＭＶ病毒,肝功能损害后治疗包括停止或减量应用有关药物,常规预防性保肝治疗,加用赛诺金、环胞菌素Ａ（ＣｓＡ）、甘昔洛韦（ＤＨＰＧ）、磷钾酸钠。结果１５例异基因ＢＭＴ（Ａｌｏ－ＢＭＴ）患者肝功能１３例有异常,２１例自体ＢＭＴ（Ａｕｔｏ－ＢＭＴ）患者１３例肝功能异常（Ｐ＜０．０５）,发生移植物抗宿主病（ＧＶＨＤ）者肝功能损害发生率高（Ｐ＜０．０５）,ＣＭＶ感染者肝功异常率高（Ｐ＜０．００１）,肝炎病毒感染者肝损发生率高（Ｐ＜０．００１）。结论ＢＭＴ患者肝功能损害与ＢＭＴ类型、ＧＶＨＤ的发生及程度及病毒感染呈显著相关。     

HA联合VP_(16)或VM_(26)治疗高危和难治性成人急性非淋巴细胞白血病

目的探讨ＨＡＥ方案联合治疗高危和难治性急性非淋巴细胞白血病的效果。方法成人ＡＮＬＬ２４例,其中慢粒急变５例,复发和难治性１３例,初治的高危患者６例。治疗方案：三尖杉酯碱（３～４）ｍｇ／ｄ、Ａｒａ－Ｃ２００ｍｇ／ｄ,ＶＰ１６或ＶＭ２６１００ｍｇ／ｄ,三种药物均静脉滴注１ｄ～５ｄ或７ｄ为一疗程;同时预防感染和出血。结果总的完全缓解率（ＣＲ）８０％（１９／２４）,达完全缓解平均需要１．３疗程,需时３０ｄ;感染发生率８７．５％,白细胞低于１．０×１０９／Ｌ占６８％,恢复至３．０×１０９／Ｌ以上平均需要２３ｄ,血小板＞５０×１０９／Ｌ平均需要１７ｄ,无因副作用而死亡者。结论ＨＡＥ方案能明显提高高危和难治性成人ＡＮＬＬ的ＣＲ率,骨髓抑制明显,毒性能够耐受。     

胃癌细胞异位分泌人绒膜促性腺激素对微血管密度的影响

目的研究胃癌组织中人绒膜促性腺激素（ＨＣＧ）对微血管密度（ＭＶＤ）的影响。方法运用ＳＰ法,对４０例胃癌手术切除标本进行抗人β促绒膜性腺激素（βＨＣＧ）多克隆抗体和抗因子ＦⅧ相关抗原抗体（ＦⅧＲＡｇ）免疫组织化学染色,观察癌组织、癌旁、正常组织各区域βＨＣＧ的表达和ＭＶＤ。结果所有胃癌组织中,βＨＣＧ仅在癌细胞内阳性表达,表达率为３７．５％（１５／４０）。ＭＶＤ在癌组织为２７．４±７．１,癌旁为１１．９±５．４,正常组织为４．８±１．５（Ｐ＜０．０５～０．０１）。βＨＣＧ阳性组的ＭＶＤ明显高于βＨＣＧ阴性组（Ｐ＜０．０５）,βＨＣＧ,ＭＶＤ和组织类型无关（Ｐ＞０．０５）,但βＨＣＧ和淋巴结转移有关（Ｐ＜０．０５）,伴有血道转移组的βＨＣＧ,ＭＶＤ均高于不伴血道转移组（Ｐ＜０．０５）。结论微血管生长与肿瘤的生长,血道转移有关,而ＨＣＧ对肿瘤的微血管有一定的促生长作用。     

耐顺铂人肺腺癌细胞系A549DDP的建立及耐药机制

采用递增顺铂（ＤＤＰ）浓度的方法，体外连续培养建成一株耐ＤＤＰ的人肺腺癌细胞系Ａ（５４９）ＤＤＰ，耐ＤＤＰ为亲代Ａ（５４９）的２４．４倍。在无ＤＤＰ的培养基中培养５月余，其耐药性仍稳定。Ａ（５４９）ＤＤＰ细胞内谷胱甘肽（ＧＳＨ）水平显著高于亲代细胞（Ｐ＜０．０１）。ＢＳＯ耗竭细胞内ＧＳＨ后，Ａ（５４９）ＤＤＰ细胞对ＤＤＰ敏感性增加５倍，ＢＳＯ对亲代Ａ（５４９）细胞无增敏作用，Ａ（５４９）ＤＤＰ细胞ＧＳＴ酶同功酶ＧＳＴ—π含量较Ａ（５４９）高１．６倍，却无ＧＳＴ基因扩增，表明ＧＳＨ／ＧＳＴ解毒系统参与Ａ（５４９）ＤＤＰ耐药性的产生。实验结果亦示Ａ（５４９）ＤＤＰ与卡铂及氨甲喋呤间存在交叉耐药，而与易产生ＭＤＲ或ａｔＭＤＲ之ＡＤＭ、ＶＣＲ、ＶＰ－１６、ＶＭ－２６无交叉耐药，Ａ（５４９）细胞无Ｐ－糖蛋白（Ｐ－ｇｐ）表达，Ｓｏｕｔｈｅｒｎｂｌｏｔ研究Ａ（５４９）ＤＤＰ无ｍｄｒｌＴｏｐｏⅡ基因扩增，提示Ａ（４５９）ＤＤＰ细胞系与ＭＤＲ及ａｔ－ＭＤＲ无交叉耐药。     

CHOP与CNOP治疗非何杰金氏淋巴瘤的对比观察报告

ＣＨＯＰ（ＣＴＸ、ＡＤＭ、ＶＣＲ、ＰＤＮ）联合化疗方案是治疗非何杰金氏淋巴瘤（Ｎｏｎ—Ｈｏｄｇｋｉｎ′ｓＬｙｍｐｈｏｍａＮＨＬ）常用的、有效的方法之一。米托蒽醌是一有效的、广谱的、细胞周期非特异性抗癌药，化学结构与阿霉素相似，抗癌活性与ＡＤＭ相当或略高，它无氨基糖结构，心脏毒性较ＡＤＭ低。对确诊为ＮＨＬ３６例住院患者，随机分为ＣＨＯＰ组和ＣＮＯＰ组各１８例作临床对比观察。ＣＨＯＰ组ＣＲ２例、ＰＲ７例，有效率５０％（９／１８）；ＣＮＯＰ组ＣＲ４例、ＰＲ７例，有效率６１．１％（１１／１８），两组疗效相似（Ｐ＞０．０５）。     

CD3AK对晚期肝癌疗效初步观察

目的观察晚期肝细胞癌（ＨＣＣ）患者采用抗ＣＤ３抗体激活的杀伤细胞（ＣＤ３ＡＫ）治疗的效果。方法５８例晚期ＨＣＣ患者分为三组，Ａ组［ＣＤ３ＡＫ＋肝动脉化学栓塞（ＴＡＣＥ）］２２例，Ｂ组（ＣＤ３ＡＫ）１５例，Ｃ组（ＴＡＣＥ）２１例。结果部分缓解率（ＰＲ）Ａ，Ｂ，Ｃ组分别为４５．５％、１３．３％（Ｐ＜０．０５）和１４．３％（Ｐ＜０．０５），中位生存期分别为１１．３月、４．９月（Ｐ＜０．０１）和４．１月（Ｐ＜０．０１），半年和１年生存率分别依次为６８．２％，３３．３％（Ｐ＜０．０５）和２３．８％以及４０．９％、６．６％（Ｐ＜０．０５）和９．５％（Ｐ＜０．０５）。结论本组结果表明ＣＤ３ＡＫ＋ＴＡＣＥ治疗晚期ＨＣＣ疗效最佳     

五联止呕方案治疗大剂量顺铂化疗引起胃肠反应的临床应用研究

作者采用前瞻性随机分组研究，自１９９３年１月～１９９４年９月，选用五联（ＨＤ－ＭＣＰ＋ＤＸＭ＋ＶｉｔＢ６＋６５４－２＋安定）、三联（ＨＤ－ＭＣＰ＋ＤＸＭ＋ＶｉｔＢ６）、二联（ＨＤ－ＭＣＰ＋ＤＸＭ）不同止呕吐方案，分别控制ＨＤ－ＰＤＤ水化治疗９０例晚期癌症病人引起的胃肠反应。结果：①五联、三联、二联组止呕吐率分别为：８０％、５５．６％、５１．２％，五联组与其它比较，Ｐ＜０．０１，有非常显著差异，三联与二联组比较，Ｐ＞０．０５，无明显差异；②合并胃病史者，五联、三联、二联组止呕吐率分别为：１５．４％、１０％、９．９％。上述结果示：五联药可能从不同环节同时阻断影响化疗引起胃肠反应的三个受体：多巴胺Ｄ２、组胺Ａ１、毒蕈硷类物质；合并胃病史，是影响止吐率的一个重要因素。五联组无一例椎体外系副反应，与应用６５４－２、安定有关。     

AEM方案联合异搏定治疗难治性急非淋白血病临床观察

ＡＥＭ方案联合异搏定治疗难治性急非淋白血病临床观察万楚成，郭仁慈我们自１９９３年１月以来，用以阿糖胞苷（Ａｒａ－Ｃ）、足叶乙甙（ＶＰ１６）、米托蒽醌（ＭＴＺ）组成的ＡＥＭ方案联合异搏定（ＶＰＭ）治疗成人难治性急性非淋巴细胞白血病（ＡＮＬＬ）１５例，现...     

帕米膦酸二钠和~(153)Sm-EDTMP治疗骨继发性恶性肿瘤疗效对比研究

帕米膦酸二钠（ＡＰＤ）与１５３钐－乙二胺四甲基膦酸（１５３Ｓｍ－ＥＤＴＭＰ）皆为治疗骨继发性恶性肿瘤的较新药物。为比较两者的治疗效果，将４２例骨继发性患者随机分为ＡＰＤ组和１５３Ｓｍ－ＥＤＴＭＰ组，每组各２１例，结果显示，ＡＰＤ和１５３Ｓｍ－ＥＤＴＭＰ组对患者骨痛缓解率分别为７６．１９％，９０．４８％（Ｐ＞０．０５）。ＡＰＤ与１５３Ｓｍ－ＥＤＴＭＰ对骨转移灶控制率分别为４７．６２％、２３．８１％（Ｐ＜０．０５）。说明ＡＰＤ对转移病灶控制的效果更佳。两种药物毒副作用不大，患者均可耐受。     

Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial

Retrospective analyses in non-randomised cohorts suggest that regimens containing fludarabine/Ara C and/or idarubicin/ara C may be more effective than daunorubicin/AraC (DA)-containing regimens in cases of acute myeloid leukaemia (AML) overexpressing p-glycoprotein (Pgp). We prospectively measured Pgp protein and function by flow cytometry in CD45-gated blasts from 434 AML15 trial patients randomised to remission induction therapy with two courses of FLAG-Ida or DA±etoposide (DA/ADE). In all, 34% were positive for Pgp protein and 38% for function. Pgp protein-positive cases had a higher incidence of resistant disease (14% vs 5%), adjusted odds ratio 2.67 (1.14-6.24). There was a trend towards a higher cumulative incidence of relapse at 5 years for Pgp-positive cases (46% vs 55%), adjusted hazard ratio 1.42 (0.98-2.07) (P=0.06). For patients treated with FLAG-Ida, the complete remission (CR) rate was 86% for both Pgp-positive and Pgp-negative patients. In patients treated with DA/ADE, 78% of Pgp-positive and 90% of Pgp-negative cases achieved CR (P=0.06). In analyses of overall survival, there was no interaction between treatment received and Pgp expression. Data for Pgp function followed similar trends. Our data suggest that FLAG-Ida may improve the remission rate for Pgp-positive AML, but the malignant clone is reduced rather than eradicated such that the relapse rate remains high in Pgp-positive patients.     

Mitoxantrone versus doxorubicin in combination chemotherapy for advanced carcinoma of the breast

One hundred fifteen patients with metastatic carcinoma of the breast were treated in a randomized trial of mitoxantrone (Novantrone, Lederle Laboratories, Pearl River, NY) combined with vincristine and prednisolone (VMP) or doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) combined with vincristine and prednisolone (VAP). In 100 evaluable patients, the objective response rates were 35% for VMP and 61% for VAP, the complete response rates being 6% and 13%, respectively. In responding patients, median time to progression was 6.2 months for VMP and 7.9 months for VAP. The median survival whether measured from primary diagnosis, first metastasis, or from the start of chemotherapy was similar for both regimens. Toxicity, particularly alopecia, was appreciably lower in the VMP treated patients, but subclinical cardiotoxicity was seen within the scheduled dosage for both combinations. We conclude that VAP is clearly more active, but clinically more toxic than VMP. There is no survival advantage conferred by the more toxic combination. Cardiac toxicity is a potential hazard with either drug combination.     

门冬酰胺酶诱导缓解治疗急性非淋巴细胞白血病16例

目的探讨门冬酰胺酶(Aase)对急非淋巴细胞白血病(ANLL)诱导缓解的影响.方法用Aase联合常规HA(三尖杉酯碱、阿糖胞苷)、DA(柔红霉素、阿糖胞苷)、维甲酸和砷剂等方案治疗了16例ANLL患者.结果16例中有14例CR,总CR率87.5%.结论①Aase对无论是初治、复发还是耐药ANLL都有着明显的疗效;②Aase对CNSL具有防治作用.     

Small noncleaved cell lymphoma in adults: superior results for stages I-III disease

Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5-year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage.     

急性单核细胞白血病46例临床分析

目的：探讨急性单核细胞白血病的临床特征和化疗疗效。方法：分析46例急性单核细胞白血病的临床资料。结果：M5约占急性髓系白血病21.2％，男性青壮年多见，漫润症状明显，部分以全血细胞减少起病。总缓解率54.3％。结论：以米托蒽醌为主的化疗方案较DA或HA方案疗效好，巩固治疗以造血干细胞移植和有HD-Ara-C在内的方案为佳。     

全反式维甲酸联合高三尖杉酯碱治疗急性早幼粒细胞白血病的临床研究

 目的 研究全反式维甲酸（ATRA）联合高三尖杉酯碱（HHT）治疗急性早幼粒细胞白血病（APL）的可行性、疗效及不良反应。方法 选择初诊的APL患者26例随机分为研究组和对照组,分别给予ATRA或柔红霉素（DRN）／米托蒽琨（Mit）联合HHT诱导治疗,HA或DA／MA方案巩固治疗。在诱导及巩固治疗各疗程结束时分别对比两组病例的CR率、融合基因情况、不良反应及无病生存期（DFS）,并进行统计学分析。结果 研究组在诱导结束时全部病例获血液学缓解,缓解率为100 ％,融合基因转阴率为63.6 %。巩固第一疗程结束时融合基因转阴率为100 ％（至随访截止时间）。累计生存率为85.7 ％。诱导治疗期间中位累计血浆输注量为670 ml,中位累计血小板输注量32 U。对照组1例患者早期死亡,诱导结束时其余病例获血液学缓解。融合基因转阴率为38.5 %,巩固第一疗程结束时融合基因转阴率为91.7 %,累计生存率为75.6 ％。诱导治疗期间中位累计血浆输注量为760 ml,中位累计血小板输注量32 U。两组比较,在疗效、融合基因转阴率、累计生存率（85.7 %／75.6 %）及不良反应等方面均相似,在诱导治疗融合基因转阴率方面研究组似有优势,差异无统计学意义。结论 ATRA联合HHT治疗APL在疗效、融合基因转阴率、血浆及血小板输注量及不良反应方面差异无统计学意义,作为新诊断APL治疗的新选择,也可取得分子生物学缓解。     

A prospective study of a new combination chemotherapy regimen in patients older than 70 years with unfavorable non-Hodgkin's lymphoma.

PURPOSE: A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma (NHL), was undertaken. PATIENTS AND METHODS: Between January 1987 and April 1990, 52 consecutive unselected patients older than 70 years (median age, 75.6 years) with stage I to IV intermediate- and high-grade NHL, or with stage III to IV low-grade malignancy with symptomatic disease received etoposide and prednimustine 80 mg/m2 orally for 5 days and mitoxantrone 8 to 10 mg/m2 day 1 intravenously (IV), every 21 days. Fourteen patients were previously treated. RESULTS: Among the 48 assessable patients, the objective response rate was 81%; 46% of the patients achieved a complete response (CR). The overall toxicity seemed to be acceptable, with 15 (7%) episodes of grade 4 leukopenia and 41 (18%) episodes of grade 3, over a total of 226 administered cycles. The median survival was 12 months. The patients who obtained CR have a longer survival than those who did not (34 v 8 months; P less than .001). Fifty-eight percent of patients achieving CR were free from relapse at 24 months; up to 36 months from the start of therapy, 25% were free from relapse. As far as patients affected by diffuse histiocytic lymphoma, 66% of previously untreated patients obtained a CR, and 55% of them were still disease-free at 24 months from the start of therapy. CONCLUSION: We conclude that VMP is effective, well tolerated, and feasible on an outpatient basis in an unselected, elderly population affected by unfavorable NHL.     

Squamous cell carcinoma of the esophagus. Treatment by combined vincristine-methotrexate plus folinic acid rescue and cisplatin before radiotherapy

From January to November, 1981, 28 patients with unresectable squamous cell carcinoma of the esophagus were treated with two cycles of chemotherapy combining vincristine (V), methotrexate (M), folinic acid rescue, and cisplatin (P) on days 1 and 21. Split-course radiation therapy was delivered thereafter from day 42 on. Hematologic, renal, and neurologic tolerance was acceptable, but most of the patients experienced nausea and vomiting. Results evolution at day 40 showed a 61% partial response (PR) rate and a 7% complete response (CR) rate. One month after the end of radiation therapy, 43% PR and 32% CR were obtained. Median response duration was 8 months. Median survival was 11.6 months for patients overall, yielding 12.9 months for responders and 5.9 months for nonresponders. Based on the response rate obtained with combined chemotherapy, a randomized trial of VMP initial chemotherapy is currently being undertaken by our cooperative group to study whether such an initial treatment could improve resectability and radiation-mediated local control along with survival rate.     

序贯诱导法治疗高危急性非淋巴细胞白血病

 目的　探讨小剂量HA（LD-HA）方案及标准方案序贯诱导法治疗高危急性非淋巴细胞白血病（ANLL）的疗效。方法　对50例不适合常规诱导的高危ANLL患者（LD-HA组）进行了序贯诱导。第1个周期诱导方案为LD-HA,首次诱导仍未缓解者,更换为标准方案（DA或HA）诱导。选择同期以DA或HA方案诱导治疗的23例ANLL患者（DA／HA组）作为对照,最多诱导2个周期。结果　LD-HA组患者完全缓解率为80.0 %（40／50）,诱导过程死亡2例;中位无瘤生存时间为19.6个月,中位生存时间为12.2个月;1、3、5年生存率分别为57.0 %、24.1 %、18.8 %。DA／HA组共17例完全缓解,缓解率为73.9 %;中位无瘤生存时间为19.8个月,中位生存时间为12.1个月;1、3、5年生存率分别为56.58 %、27.1 %、27.1 %,两组相比,1、3、5年生存率差异无统计学意义（χ2值分别为0.009、0.237、1.807,P值均＞0.05）。结论　以LD-HA及标准方案序贯诱导高危ANLL患者,可获得较高的完全缓解率及长期生存率。