急性髓性白血病抑制NK细胞功能的实验研究

NK细胞是肿瘤免疫监视的第一道防线,搞清肿瘤病人NK细胞活性下降的机理是提高肿瘤病人NK细胞功能的前提,也是肿瘤免疫治疗获得成功的关键。我们抽取9例急性髓性白血病(AML)病人的外周血,发现其血清和幼稚细胞(即白血病细胞)培养上清具有抑制NK细胞功能的作用,抑制作用的强弱与孵化正常NK细胞的时间相关。对照组用正常同种异体血清和正常人骨髓单个核细胞培养上清孵化,不呈现抑制作用。本实验提示血清中的抑制物质来源于白血病细胞,其抑制环节是在效靶作用之前预先作用于NK细胞。     

吸烟与白血病

有关吸烟与白血病的关系众说不一。最近有人认为吸烟是白血病的一个危险因素,并指出吸烟可能与急性粒细胞白血病(AML)有关。作者采用病例对照研究,对114名非淋巴细胞白血病(ANLL)病人和133名正常人吸烟与成人AML及其它ANLL之间的关系进行分析。     

α一干扰素和前列腺素E_1对多向造血祖细胞和白血病祖细胞的生长影响

本文认为α一干扰素在体外对正常人多向造血祖细胞有抑制作用,10u/4×10~4细胞浓度抑制率为95％,而对白血病祖细胞,1000u/4×10~4抑制率仅为25％;前列腺素E_1对多向造血祖细胞亦有抑制作用,1ug/4×10~4抑制率为77％,而对白血病祖细胞10ug/4×10~4仍无抑制作用,集落产率明显增加(P<0.01)。提示如试用白血病临床治疗时,干扰素需用大剂量,而前列腺素宜进一步探索。     

c-kit在急性白血病中的表达及其临床意义

目的 :研究c kit受体 (c kitR ,CD1 1 7)在急性白血病 (AL)中的表达。重点了解c kitR表达对急性非淋巴细胞白血病 (ANLL)的诊断价值及其与ANLL的临床和生物学特征的关系。方法 :采用流式细胞术 (FCM)分别检测并比较 2 4例急性淋巴细胞白血病 (ALL)和 47例ANLL初诊患者骨髓单个核细胞 (MNC)跨膜c kitR表达的阳性率及阳性水平 ,并设立 1 0例正常人骨髓标本作为阴性对照组。结果 :ALL患者的c kitR表达的阳性率及阳性水平与正常人相比无显著性差异 (P >0 .0 5)。ANLL患者的c kitR表达率及阳性水平则均显著高于正常人和ALL患者(P均 <0 .0 1 )。c kitR阳性率以M1 、M2 最高 ,M4最低。ANLL患者c kitR表达与外周血白细胞计数、肝脾肿大无关(P >0 .0 5) ,但与染色体核型异常及LDH水平增高有关 (P均 <0 .0 5)。结论 :ANLL患者的c kitR阳性表达率及阳性水平均显著高于正常人和ALL患者 ,提示c kitR可作为AL患者MIC分型诊断的髓系免疫表型依据 ,可用以协助ANLL的诊断以及ANLL与ALL的鉴别诊断     

PHA—LCM与HM—CM对急性髓细胞白血病集落生长的研究

急性髓细胞白血病(AML)祖细胞体外培养应用Pike和Robinson的双层琼脂培养法集落产率很低,多数为细胞簇,已见于Moore等的报道、1976年Dicke等应用植物血凝素—白细胞条件培养基(PHA—LCM),结果形成大量的白血病祖细胞集落(CFU—AML)。近来国内一些报道应用胎肌一条件培养基(HM—CM)作为集落刺激因子(CSF)用于正常粒祖细胞的     

原发性肝癌患者可溶性IL—2受体水平,IL—2和NK活性的变化及意义

采用双抗体夹心ELlSA法检测43例原发性肝细胞癌(PHC)病人血清可溶性白细胞介素2受体(sIL-2R)水平,及其外周血单个核细胞(PBMC_s)的白细胞介素2(IL—2)活性和自然杀伤(NK)细胞活性.另将51例慢性乙型活动性肝炎和肝硬化病人做为对照.结果,上述病人血清sIL—2R水平明显升高,IL—2和 NK活性低于正常人,其中PHC的IL—2和NK活性的降低又为显著(P<0.001< O.001).表明PHC病人的细胞免疫功能受损程度最重.检测sIL_2R水平和IL—2活性,可望做为对PHC患者病情分析及判断预后的指标.     

急性白血病P16基因缺失的意义

目的 探讨周期素依赖性激酶4抑制因子基因（p16）缺失在急性白血病中的意义。方法 采用PCR方法对43例急性淋巴细胞白血病（ALL）,36例急性非淋巴细胞白血病（ANLL）中p16基因的纯合缺失进行了研究。结果 21例ALL存在p16基因纯合缺失,3例ANLL存在p16基因纯合缺失。ALL p16基因缺失率明显高于ANLL（P＜0．05）,p15基因缺失的ALL病人有较高的复发率。结论 ALLp16基因缺失率较高,p16基因缺失之ALL预后不良。     

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.     

成人急性白血病550例疗效探讨

1972年以来,我们以剂量较小的联合化疗,配合中医中药及非特异性自动免疫疗法综合治疗成人急性白血病,总的完全缓解率(简称CR)为60.2％,5年生存率13.6％,8人存活逾10年,仍健在。现将成人急性白血病550例治疗结果及预后因素,报告如下: 研究对象和方法病例治疗达1疗程,可资分析疗效550例中,急性淋巴细胞白血病(ALL)150例,急性非淋巴细胞白血病(ANLL)400例,两者之比为1:2.7。诊断时年龄16～68岁,平     

急非淋白血病人外周血白细胞介素2及其受体活性和化疗对其影响的研究

为了解急性非淋巴细胞性白血病(ANLL)病人免疫功能的改变和化疗药物的影响,我们从1991年9月至1992年1月,对12例ANLL病人于化疗前后进行白细胞介素2(1L—2)和白细胞介素2受体(1L—2R)活性的检测。材料和方法一.一般资料 1.所有病例符合1986年9月天津会议所制定的诊断标准,平均为初治病人,其中男性11例,女性1例。平均年龄34岁(15--56岁)。M_11例、M_25例、M_32例、M_42例、M_51例、未定型者1例。     

Prognostic significance of general immune competence in acute leukemia

The prognostic significance of lymphocyte transformation rate, E-RFC%, 29 degrees C E-RFC%, serum IgG, IgA, IgM and C3 levels were studied in 286 patients with acute leukemia. In acute lymphoblastic leukemia (ALL), the pretreatment immunological parameters were not related to whether the patients could achieve complete remission (CR), but the patients with E-RFC% greater than 30% before treatment or E-RFC% restored to normal after treatment had a significantly longer survival time. In acute nonlymphocytic leukemia (ANLL), pretreatment LTR and E-RFC% were significantly higher in patients who could achieve CR subsequently, the patients with higher pretreatment levels of LTR, E-RFC% or 29 degrees C E-RFC% survived significantly longer than patients with lower levels of these parameters, and the patients whose LTR could return to normal after treatment had a significantly higher CR rate and longer survival times. Except that the pretreatment IgM level was related to the survival of ANLL patients, serum levels of immunoglobulins and C3 had no prognostic value for both ALL and ANLL. In both ALL and ANLL, the immunological parameters changed significantly when relapse occurred.     

急性髓系白血病细胞异常免疫表型表达的研究

应用免疫酶标染色法检测了59例急性髓系白血病（AML）患者的白血病细胞免疫表型，结果表明CD2、CD5、CD7、CD10、CD19、CD22淋系抗原的表达率分别为16．9％（10／59）、119％（7／59）、16．9％（10／59）、15．3％（9／59）、102％（6／59）和6．8％（4／59）。进一步分析结果表明，在M3病例细胞中，CD2、CD10和CD19抗原表达阳性率明显高于M5组，而CD7抗原表达阳性率则明显低于M5组。结合临床，CD2、CD19阳性的AML病例对化疗治疗及应优于CD2、CD19阴性的AML病例；CD7阳性的AML病例的疗效与预后则比CD7阴性的AML病例差。提示部分AML病例的白血病细胞存在不同程度异常免疫表型的表达，且与疗效及预后有一定关系。     

Specific chromosomal abnormalities in acute nonlymphocytic leukemia correlate with drug susceptibility in vivo

Specific chromosomal abnormalities are independent predictors of response to therapy in acute nonlymphocytic leukemia (ANLL) de novo. In a series of 149 patients with ANLL, we sought to determine whether the t(8;21), t(15;17), t(9;11) or other abnormalities of the long arm of chromosome 11, inv(16) or t(16;16), inv(3) or t(3;3), trisomy 8, and abnormalities of chromosome 5 (-5/5q-) or of chromosome 7 (-7/7q-) identify differences in susceptibility to chemotherapy drugs in vivo. The immediate outcome of the first cycle of remission induction chemotherapy was analyzed for patients in each cytogenetic subgroup as an index of the drug susceptibility of the leukemia cells in vivo. Patients with t(8;21), inv(16), t(16;16), or 11q abnormalities had high rates of complete remission after initial therapy (60-100%), whereas patients with -7/7q- or -5/5q- had low initial response rates (0-36%), suggestive of drug resistance in vivo. In general, cytogenetic groups with high initial complete remission rates ("drug sensitive") also had long disease-free survivals; those groups with low initial remission rates ("drug resistant") had short remission durations even if these patients eventually achieved complete remission with further therapy. Patients with acute promyelocytic leukemia (APL), all of whom had the t(15;17), were the exception; despite low initial remission rates, they had long disease-free survivals, possibly due to a more rapid cytotoxic effect of chemotherapy on the clonogenic APL cells than on the more numerous malignant promyelocytes. We conclude that the prognostic importance of specific chromosomal abnormalities in ANLL resides in part in differing susceptibilities to chemotherapy.     

Prednimustine and vincristine compared with cytosine arabinoside and thioguanine for treatment of elderly patients with acute nonlymphoblastic leukemia

Summary Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine+vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside+thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine+vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.     

Impaired cell-mediated immunity in patients with cancer.

The ability of peripheral blood lymphocytes to respond in vitro to phytohemagglutinin (PHA) and to allogeneic cells in mixed leukocyte reaction (MLC) was studied in 85 patients with cancer and in 50 healthy controls. The effect produced by sera from cancer patients on in vitro lymphocyte blastogenesis was tested on autologous cells and on homologous cells from a constant panel of 10 normal volunteers. Patients with cancer showed a distinct deficiency of cellular immune responsiveness reflected in a stage-related impairment of PHA and MLC reactivity. This deficiency seems at least partially attributable to the presence of lymphocyte depressive factors in cancer sera, since such sera reduced the reactivity of both autologous and normal homologous lymphocytes to a level that was significantly lower than that found in the presence of pooled normal serum. The inhibitory activity of cancer sera was directly related to the extent of the neoplasia.     

Response to 5-azacytidine in patients with refractory acute nonlymphocytic leukemia and association with chromosome findings

Fifteen patients with acute nonlymphocytic leukemia (ANLL) who either had a relapse after a previous complete remission (nine patients) or progressive disease after initial induction attempts with combination chemotherapy (six patients) were treated with 5-azacytidine. Five patients (33%) achieved a complete remission (CR); of these, three had a relapse and died 30, 35, and 38 weeks after 5-azacytidine therapy was begun. Two patients are still alive at 39 and 138 weeks. Chromosomes were analyzed at the time of diagnosis; ten patients had a normal karyotype and five had an abnormal karyotype. Three of the five CR patients had an abnormal karyotype initially. Two of these individuals had a translocation of chromosomal material from a No. 8 chromosome to a No. 21 chromosome, t(8;21); this particular translocation has been associated with a better prognosis than have other types of chromosomal abnormalities in patients with ANLL. Even when abnormal chromosomes are present, 5-azacytidine can induce complete remission in patients with previously treated ANLL.     

联合去甲氧柔红霉素治疗急性白血病的临床研究

采用以４－去甲氧基柔红霉素（ＩＤＡ）为主组成的联合化疗方案，治疗３３例初发和复发的急性白血病，其中急性淋巴细胞白血病（ＡＬＬ）７例，急性非淋巴细胞白血病（ＡＮＬＬ）２６例。结果：总有效率７０％。初治２３例ＡＮＬＬ患者，完全缓解（ＣＲ）１６例，部分缓解（ＰＲ）２例，有效率为７９％。５例初治ＡＬＬ患者，４例ＣＲ，１例ＰＲ。而复发的２例ＡＬＬ和３例ＡＮＬＬ患者均未缓解。ＩＤＡ主要副作用表现为骨髓抑制及心脏毒性。认为以ＩＤＡ组成联合化疗方案治疗初发的急性白血病具有较好的疗效     

4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA) in the treatment of relapsed adult acute leukemia

Between March 1980 and December 1981, 22 patients were treated with 4'(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA), each given by I.V. push in a dosage of 150 mg/m2 for 5 days. Seven of 12 prior-remitting, acute nonlymphoblastic leukemia (ANLL) patients achieved complete remission (58%). Six ANLL patients who failed to remit on standard daunorubicin-cytosine arabinoside programs also failed to remit on the m-AMSA-AZA combination. Two patients with relapsed acute lymphatic leukemia (ALL) also failed while two patients with chronic myelocytic leukemia (CML) in evolution were cytoreduced. The seven patients who achieved remission had additional relapse-free survival for a median of six months (range 1-23+ months). One patient obtained a second remission with m-AMSA-AZA after relapse which followed a 9-month period of nonmaintained remission. Most patients demonstrated mild to moderate nausea and vomiting. Hepatic toxicity was mild to infrequent. Only four patients showed cardiac toxicity which was not life-threatening. The most troublesome toxicity was mucositis and was seen in 11 patients; four whom required I.V. hyperalimentation. We conclude that this combination is an effective salvage program for relapsed prior-remitting ANLL. Future studies should be conducted in three areas. The first study might be a comparison of relapsed prior-remitting ANLL with single-agent m-AMSA. The second, in untreated ANLL, following induction with DAT, might use m-AMSA-AZA in consolidation and maintenance arms of future protocols. The final study should explore m-AMSA-AZA activity in evolved CML in a greater number of patients.     

Prognostic significance of terminal deoxynucleotidyl transferase activity in acute nonlymphoblastic leukemia

Bone marrow and/or peripheral blood samples from 133 (75%) of a total of 177 consecutive previously untreated protocol patients with acute nonlymphoblastic leukemia (ANLL) were analyzed for terminal deoxynucleotidyl transferase (TdT) activity at the time of presentation. Twenty-nine (22%) were found to exhibit TdT activity (greater than or equal to 0.10 U/10(8) cells, TdT+) as measured in a biochemical microassay. There were no differences between TdT+ as compared with TdT-negative (TdT-) patients with respect to age, sex, French-American-British (FAB) classification, or the presence of Auer's rods. Remission induction rates were higher for the TdT- patients, with 68% v 48% for the TdT+ patients (P = .05). TdT- patients also experienced longer remissions (P = .003) than TdT+ patients, especially in the Auer's rod-positive subgroup (P = .002). None of five patients with TdT+ ANLL treated with vincristine and prednisone as initial therapy achieved complete remission; all required induction regimens containing daunorubicin or amsacrine in combination with cytosine arabinoside and 6-thioguanine. It is concluded that TdT activity in ANLL indicates biphenotypia or lineage infidelity and is associated with a poor prognosis on chemotherapy protocols currently used for the treatment of ANLL.     

Cell kinetics with in vivo bromodeoxyuridine assay,proliferating cell nuclear antigen expression,and flow cytometric analysis. Prognostic significance in acute nonlymphoblastic leukemia

Background. The proliferative characteristics of acute nonlymphoblastic leukemia (ANLL) were studied in vivo, and data were correlated with response to chemotherapy and survival. Methods. Sixty-five patients with untreated ANLL and 15 patients with solid tumors and normal bone marrow (BM) received 250 mg/m² of bromodeoxyuridine (BUdR); bivariate flow cytometric (FCM) analysis then was used to measure cell BUdR incorporation and DNA content to obtain a complete set of kinetic parameters (i.e., BM BUdR-labeling index, DNA-synthesis time, potential doubling time [Tpot], and cell production rate). The percentage of blasts with positive results for proliferating cell nuclear antigen (PCNA) also was obtained by FCM analysis on the same BM samples, and these kinetic parameters were derived specifically for the ANLL proliferating compartment (growth fraction). Induction therapy, consisting of vincristine, arabinosylcytosine, and daunomycin, was administered subsequently to the patients with ANLL. Results. Overall ANLL proliferative activity was lower than normal myelopoiesis, and a short Tpot was found to be a favorable factor for achieving complete remission (CR), the duration of CR, and survival. When the growth fraction was considered, however, ANLL proliferative activity was higher and more like that of normal BM. The kinetic differences detected in the PCNA-positive cells of patients with CR and no response and those with CR and survival durations above and below the median values for the entire series were highly significant in univariate analysis and retained a strong independent prognostic value when multivariate analysis was performed. Conclusions. These data show the clinical feasibility of a detailed study of cell kinetics by means of new FCM-based techniques and reinforce the clinical value of pretreatment proliferative activity in ANLL.