TA方案治疗老年急性髓系白血病

目的：观察TA方案治疗老年急性髓系白血病的疗效。方法：THP 20mg／d静脉滴注，第1天-第3天，Ara-C200mg／d分两次静脉滴注，间隔12h，第1天。第5天或第1天-第7天；每疗程3周一4周。完全缓解后原方案巩固2个疗程，然后换用HA、EA和TA方案交替巩固和维持化疗。结果：20例中完全缓解(CK)13例(65％)，部分缓解(PK)3例，未缓解4例，总有效率80％。结论：TA方案具有高效低毒特点，尤其适合老年急性髓系白血病选用其他蒽环类药物困难时采用。     

吡柔比星为主方案治疗老年急性髓系白血病

吡柔比星(pirarubicin,THP),亦名吡喃阿霉素,是新一代蒽环类抗癌抗生素.     

重组人粒系集落刺激因子对白血病细胞的作用

作者观察了重组人粒系集落刺激因子（ｒｈＧ－ＣＳＦ）对ＨＬ－６０细胞和原代培养的急性髓系白血病（ＡＭＬ）细胞的作用，结果显示，ｒｈＧ－ＣＳＦ可刺激白血病细胞生长，并诱导部分ＡＭＬ细胞向粒系分化。提示ｒｈＧ－ＣＳＦ对白血病细胞存在着增殖与分化的双重作用，这种作用对改进白血病治疗可能产生重要影响。     

重组粒细胞集落刺激因子在儿童急性粒白血病中的应用

目的研究用重组粒细胞集落刺激因子(rhG-CSF)对强烈化疗后急性白血病患儿中性粒细胞严重低下的治疗作用.方法比较强烈化疗后急性白血病患儿用重组粒细胞集落刺激因子组(n=136)与对照组(n=65)中性粒细胞绝对值(ANC)的降低时间、感染发生率及严重程度.结果ANC≥0.5×109/L的时间,治疗组比对照组明显者缩短(P＜0.05),感染发生率和严重程度明显亦降低.结论应用重组粒细胞集落刺激因子后可使粒细胞计数和功能恢复快,感染发生率和严重程度减少,并可减少经济负担.     

氟达拉滨联合中剂量阿糖胞苷和粒细胞集落刺激因子治疗复发和难治性急性髓系白血病

新型核苷类似物氟达拉滨（Fludarabine,rA）对慢性淋巴细胞白血病和惰性淋巴瘤具有较好的疗效,已被人们所接受。临床研究表明,FA对难治性急性髓系白血病（AML）也有较好疗效,完全缓解率达到50％～80％。我们自2003年7月～2007年5月采用FA联合中剂量阿糖胞苷（Ara-C）和粒细胞集落刺激因子（G-CSF）治疗12例复发和难治性急性髓系白血病,取得了较好的疗效,现报告如下。     

粒细胞集落刺激因子在急性髓系白血病缓解期化疗中的费用效果分析

 目的 探讨急性髓系白血病缓解期化疗后应用G-CSF的必要性。方法 采用自身前后对照,比较了24例急性髓系白血病患者两次化疗后用与不用G-CSF的感染率、感染时间和医疗费用情况。结果 用与不用G-CSF感染率分别为79.2 %和87.5 %,差异无统计学意义（P＞0.05）;用G-CSF较未用感染时间要缩短（1.75±1.69）d（P＜0.01）;用G-CSF者的医疗费用要超过未用者（P＜0.05）。结论 急性髓系白血病患者缓解期常规方案化疗后使用G-CSF有利于缩短感染期,但从经济上考虑预防性使用G-CSF是非必需的。     

影响老年急性髓系白血病患者预后的危险因素分析

目的 探讨影响老年急性髓系白血病患者预后的危险因素.方法 回顾性分析121例老年急性髓系白血病患者的临床资料.对比不同临床资料患者的完全缓解率和中位生存期.通过多因素Cox模型分析统计影响老年急性髓系白血病患者预后的危险因素.结果 本研究患者的中位生存期为131 d(95%可信区间109~154 d),诱导化疗后的完全缓解率为29.75%.年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的完全缓解率升高(P﹤0.05);年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、初治时的白细胞计数≤50×109/L、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的中位生存期延长(P﹤0.05);多因素Cox模型分析结果显示,年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素(P﹤0.05).结论 年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素.临床应通过整体评估,制定个体化的化疗方案,以改善患者的预后.     

老年急性髓系白血病疗效观察

1995年9月—2001年6月收住老年急性髓系白血病(AML)48例，应用联合化疗或诱导分化治疗，进行疗效观察，现报告如下。……     

G-CSF联合GM-CSF及高剂量G-CSF治疗急性髓系白血病化疗后中性粒细胞缺乏的疗效观察

目的:探讨高剂量G-CSF方案和G-CSF联合GM-CSF方案治疗及预防急性髓细胞白血病化疗后粒细胞减少的临床疗效与安全性。方法:回顾性分析53例接受化疗的急性髓系白血病患者,对比常规剂量G-CSF、高剂量G-CSF以及G-CSF联合GM-CSF在化疗后的应用,观察中性粒细胞绝对值、中性粒细胞减少持续时间、中性粒细胞减少伴发热发生概率及各组治疗不良反应的区别。结果:高剂量G-CSF组与G-CSF联合GM-CSF组较标量G-CSF组中位ANC减少的持续时间明显缩短,中性粒细胞减少合并感染的发生率明显减少,高剂量G-CSF组与G-CSF联合GM-CSF组之间无统计学差异,三组之间安全性相仿。结论:G-CSF联合GM-CSF方案以及高剂量G-CSF方案治疗及预防急性髓细胞白血病化疗后粒细胞减少安全有效。     

基因重组人粒细胞集落刺激因子在急性白血病化疗后的临床应用

目的：急性白血病,大剂量化疗后,白细胞平均降至１ ．０３３ ×１０９／Ｌ 时,应用重组人粒细胞集落刺激因子（ｒｈＧ－ ＣＳＦ） , 使白细胞恢复。方法： 每天２５０μｇ 皮下注射, 直至连续两次复查中性粒细胞绝对计数（ＡＮＣ） 超过１ ．５ ×１０９／Ｌ 后停药,平均用药时间５ ．９ 天。结果：与未采用ｒｈＧ－ ＣＳＦ 治疗的对照组１３ ．２ 天ＡＮＣ 超过１ ．５ ×１０９／Ｌ 相比,粒细胞缺乏的恢复时间明显缩短。ｒｈＧ－ ＣＳＦ 能够明显增加白血病患者化疗后白细胞的恢复,缩短白细胞减少症的恢复时间。结论：ｒｈＧ－ ＣＳＦ 能够保证白血病患者接受并完成强烈化疗,从而提高患者生存率。     

Proliferative Effect of Human Granulocyte Colony-stimulating Factor on Blast Cells of Acute Promyelocytic Leukemia

The effect of human granulocyte colony-stimulating factor (G-CSF) on leukemic cells of acute promyelocytic leukemia (APL) was examined. Mononuclear cells obtained from bone marrow cells containing more than 90% blasts from seven APL patients were incubated in the presence of G-CSF using semisolid and liquid culture systems. On day 7, the cells from all the patients produced many clusters consisting of 8–40 cells. These cells appeared to be promyelocyte-like blast cells in four patients and had differentiated to more mature neutrophils in three patients. On day 14, the number of clusters decreased except for two patiens. Blast cells from the two patients showing the increase of blast clusters could proliferate in a liquid culture containing G-CSF. Blast cells cultured for 14 days formed many secondary cultures after replating on a methylcellulose medium. Moreover, chromosomal analyses of blasts cultivated in the presence of G-CSF for 7 days showed t(15;17) in all metaphases in one patient. It appears that the leukemic cells from APL patients could proliferate in the presence of G-CSF.     

Granulocyte Colony-stimulating Factor-dependent Growth of an Acute Myeloblastic Leukemia Cell Line

We report herein the establishment and characterization of a granulocyte colony-stimulating factor (G-CSF)-dependent acute myeloblastic leukemia (AML) cell line. The cell line, designated as OCI/AML 1a, has been cultured in the presence of G-CSF and has shown exponential growth for over two years. The cells growing in suspension culture resembled myeloblasts on the basis of morphologic, cytochemical and surface phenotypic analyses. Other CSFs, interleukin-3 and granulocyte-macrophage colony-stimulating factor did not support the growth of OCI/AML 1a cells so well as G-CSF. The effect on the growth of OCI/AML 1a cells of G-CSF was almost completely abolished by neutralizing monoclonal anti-G-CSF antibody. These findings showed that OCI/AML 1a cells required G-CSF for growth. OCI/AML 1a cell line will be valuable for studies of the biological nature, proliferation and differentiation of leukemic cells. Furthermore, OCI/AML 1a cells should be useful for determining the mechanism by which G-CSF induces the growth of hemopoietic cells.     

Effects of Interleukin-6 and Granulocyte Colony-stimulating Factor on the Proliferation of Leukemic Blast Progenitors from Acute Myeloblastic Leukemia Patients

The effects of recombinant human interleukin-6 (rh IL-6), which has homology with rh granulocyte colony-stimulating factor (rh G-CSF) at the amino acid sequence level, and rh G-CSF on normal human bone marrow cells, fresh leukemic blast progenitors from 16 acute myeloblastic leukemia (AML) patients, and G-CSF-dependent human AML cell line (OCI/AML 1a) were investigated. rh G-CSF stimulated the proliferation of leukemic blast progenitors from 13 out of 16 AML patients tested. rh IL-6 stimulated the proliferation of blasts from eight AML patients and enhanced the G-CSF-dependent proliferation of the fresh AML blasts from two out of eight patients tested. On the other hand, rh IL-6 suppressed the blast colony formation from two AML patients and OCI/AML 1a cells and also reduced the G-CSF-dependent proliferation of the blast progenitors from one of the two patients and the cell line. rh IL-6 had no effect on the colony formation of normal granulocyte-macrophage colony-forming units (CFU-GM) with or without rh G-CSF. Differentiation-induction by rh IL-6 was not observed in the fresh AML blasts but was observed in OCI/AML 1a. The effect of IL-6 on the blast colony formation and G-CSF-dependent blast cell growth was complicated and heterogenous among the AML cases; IL-6 stimulated blast colony formation in some cases and suppressed it in others. The heterogeneity of the response was supposed to be derived from the heterogeneity of the characteristics of AML cells. Although G-CSF simply stimulated the blast colony formation, IL-6 had a bimodulatory effect on the proliferation of leukemic blast progenitors from AML patients. IL-6 might be involved in the regulation of the proliferation of AML cells in vivo as well as in vitro.     

Anti-tumor Effects of Hyperthermia Plus Granulocyte Colony-stimulating Factor

The role of neutrophils in the anti-tumor effects of hyperthermia was investigated in an experimental rat model, and the efficacy of hyperthermia combined with recombinant human granulocyte colony-stimulating factor (G-CSF) was similarly investigated. AH109A carcinoma cells were transplanted into the hind legs of Donryu rats, then heated by a radio-frequency dielectric heater. In this study, because the myeloperoxidase (MPO) activity of neutrophils was not affected by heating or G-CSF, MPO activity was measured as an index of neutrophil migration into tumor tissue. After hyperthermia, MFO activity in tumor tissue increased significantly, suggesting migration of neutrophils into tumor tissue. Depletion of circulating neutrophils by the intraperitoneal injection of anti-rat neutrophil antibody decreased the anti-tumor effects of hyperthermia. Subsequently, we used hyperthermia plus intraarterial G-CSF to enhance the anti-tumor effect. Hyperthermia was induced 1 h after injection of G-CSF, a time when MPO activity in tumor tissue was maximal. A satisfactory thermal effect was noted even in cases where tissue could not be heated sufficiently. In conclusion, neutrophils have an important role in the anti-tumor effects of hyperthermia, and administration of G-CSF enhances these effects.     

胃癌患者血清G—CSF和C—反应蛋白的检测及其临床意义

目的：探讨胃癌患者血清粒细胞集落刺激因子（Ｇ－ＣＳＦ）和Ｃ－反应蛋白（ＣＲＰ）水平的变化其临床意义。方法采用ＥＬＩＳＡ法测定４７例胃癌患者血清Ｇ－ＣＳＦ和ＣＲＰ水平,并与胃良性肿瘤组和正常对照组进行比较分析。结果胃癌患者血清Ｇ－ＣＳＦ和ＣＲＰ水平明显增高（Ｐ〈０．０１）,并与疾病的临床分期和肿瘤的分化程度有关（Ｐ〈０．０５）,病灶切除后血清Ｇ－ＣＳＦ和ＣＲＰ水平明显降低（Ｐ〈０．０１）。结论血清Ｇ     

Hematologic and Cytogenetic Findings in Myelodysplastic Syndromes Treated with Recombinant Human Granulocyte Colony-stimulating Factor

We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) to four patients with myelodysplastic syndrome (MDS) and three patients with non-MDS (two malignant lymphoma and one lung cancer) as a part of a phase II trial and analyzed the effects of rhG-CSF on the neoplastic cells of MDS by performing sequential chromosome analyses on the bone marrow cells. A greater than 3-fold increase in neutrophil count was observed in the MDS patients after rhG-CSF infusions, whereas the number of blasts in the bone marrow did not increase and none of them progressed into the leukemic phase. After rhG-CSF treatment, the bone marrow cells obtained from patients without MDS did not show any particular chromosome abnormalities such as chromosomal breakage. On the contrary, two of the four MDS patients with acquired chromosome abnormalities showed a change in the frequency of marrow cells with clonal abnormalities after rhG-CSF treatment; the proportion of metaphase cells with additional numerical chromosome abnormalities decreased in these two MDS patients. After discontinuation of the treatment, the constitution of marrow cells with chromosome changes reverted to that before treatment. The remaining two MDS patients did not show any particular chromosome changes after the rhG-CSF treatment, indicating that rhG-CSF may not promote the characteristics of dyshematopoiesis in MDS, and act on cells derived from an MDS clone
.     

低剂量格拉诺赛特（rhG－CSF）防治肺癌CE方案化疗后中性粒细胞减少症的临床研究

作者采用随机分组、自身交叉对比的方法，观察了低剂量格拉诺赛特（Ｇｒａｎｏｃｙｔｅ，ｒｈＧ－ＣＳＦ）对２２例肺癌ＣＥ方案（卡铂＋足叶乙甙）化疗后白细胞和中性粒细胞减少症的防治作用及毒副反应。患者随机分成Ａ、Ｂ两组（各１１例）。Ａ组第一周期化疗后加用格拉诺赛特，第二周期单用化疗；Ｂ组第一周期单用化疗，第二周期化疗后加用格拉诺赛特。格拉诺赛特在化疗药物未次给药后４８ｈ起，５０μｇ１次／日皮下注射。结果表明，该剂量的格拉诺赛特可以明显减轻化疗过程中白细胞和中性粒细胞下降的程度，降低中性粒细胞严重降低的发生率，缩短其在正常值以下的持续时间，促进早日恢复，缩短化疗周期的间隔时间，使化疗可以如期进行。低剂量的格拉诺赛特疗效确切，副反应轻微。     

In vivo Tumor Growth Enhancement by Granulocyte Colony-stimulating Factor

The intraperitoneal administration of human recombinant granulocyte colony-stimulating factor (G-CSF) enhanced the growth of intradermally inoculated tumor in mice; in a Meth A fibrosarcoma model, G-CSF administration significantly shortened the latency before tumor appearance, accelerated the increase of tumor size, shortened the survival time of tumor-bearing mice and increased the incidence of lethal tumor growth. A similar growth-enhancing effect of G-CSF was observed in models employing Meth 1 fibrosarcoma, colon carcinoma 26, and L1210 leukemia, although not all the effects were statistically significant. In vitro study showed that G-CSF did not enhance Meth A growth in suspension culture or in soft agar. These data suggest that G-CSF enhances the Meth A growth not directly but through the mediation of host factors. The accumulation of neutrophils was histologically observed in the tumor nodule, the blood, and the spleen in mice given G-CSF repeatedly. The spleen cells and the peripheral blood leukocytes of G-CSF-injected mice enhanced Meth A growth in vitro as compared with those of mice injected with physiological saline. These results suggest the possibility that the in vivo growth of tumor cells was enhanced by G-CSF-induced overproduction of cells including neutrophils.     

Comparison of Peripheral Blood Stem Cells Mobilized with Granulocyte Colony-stimulating Factor with or without Prior Standard-dose Chemotherapy in Patients with Malignancy

We studied the effect of granulocyte colony-stimulating factoron the magnitude of peripheral blood stem cell mobilizationin patients with malignancy. The leukapheresis products mobilizedwith granulocyte colony-stimulating factor alone at a steadystate (a period of full hematopoietic recovery) (group 1) werecompared with those obtained after cytotoxic chemotherapy usinggranulocyte colony-stimulating factor (group 2). In group 1,six patients underwent six courses of stem cell collection witha median of 20 l leukapheresis. In group 2, 10 patients underwent12 courses of stem cell collection with a median of 10 l leukapheresis.Median yields of group 1 vs. group 2 were mononuclear cells(x10⁹), 21.9 vs. 11.6; CD34⁺ cells (x10⁶/l), 14.5 vs. 17.1;colony-forming unit for granulocyte-macrophage (/ml), 223 vs.1193; burst-forming unit for erythroid (/ml), 29 vs. 71; colony-formingunit for erythroid (/ml), 42 vs. 29; colony-forming unit formegakaryocyte (/ml), 26 vs. 59. While there were no statisticallysignificant differences in the number of CD34⁺ cells betweenthe two groups, granulocyte-macrophage-committed progenitorcells were more enriched in the apheresis products of group2. The correlation between CD34⁺ cells and colony-forming unitfor granulocyte-macrophage was poor. Our results demonstratethat granulocyte colony-stimulating factor can mobilize a sufficientnumber of progenitor cells into the peripheral blood for stemcell transplantation with or without prior chemotherapy.