Plasma lactic dehydrogenase and phosphohexose isomerase in leukemia

Two enzymes, lactic dehydrogenase (LD) and phosphohexose isomerase(PHI), were measured in the plasma of 30 patients with leukemia and compared with the findings in 66 control subjects. Abnormally elevated PHIlevels were found in both acute and chronic myelocytic leukemia, but notin lymphocytic leukemia. The plasma LD was increased above normal inacute and chronic myelocytic leukemia, in acute lymphocytic, but not inchronic lymphocytic leukemia. Both enzymes were normal or only slightlyraised in three patients with the aleukemic type of the disease. Hemolyticanemia in seven leukemic patients was associated with high plasma LD valuesin the presence of relatively low PHI levels.

Results of serial enzyme studies from the time of diagnosis until deathindicated that both plasma enzymes, but especially the LD, usually reflectedchanges in the course of the disease-falling during remissions and risingduring relapses. In most cases this enzyme paralleled the leukocyte levelbut occasionally indicated the onset of a relapse or remission before thewhite cell count had begun to change.

Submitted on June 28, 1957 Accepted on November 18, 1957     

Combined assay of adenosine deaminase, purine nucleoside phosphorylase, and lactate dehydrogenase in the early clinical evaluation of B-chronic lymphocytic leukemia

The levels of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), lactic dehydrogenase (LDH), and LDH isoenzyme patterns (LD1 to LD5) have been measured in lymphocyte extract from 28 patients with B-chronic lymphocytic leukemia (B-CLL). The activities of ADA, PNP, and LDH have been correlated with two morphological groups of B-CLL classified according to the percentage of large, nongranular, atypical lymphocytes (AL) in peripheral blood: "typical" B-CLL (less than 10% of AL, 21 cases) and "atypical" B-CLL (10-25% of AL, seven cases). Patients with atypical B-CLL had significantly (P less than 0.001) higher activities of ADA (0.46 +/- 0.17 U/10(9) cells), PNP (1.74 +/- 1.0 U/10(9) cells), and LDH (48.3 +/- 9.7 U/10(9) cells) than patients with typical B-CLL (ADA, 0.29 +/- 0.1 U/10(9) cells; PNP, 0.58 +/- 0.23 U/10(9) cells; and LDH, 29 +/- 10 U/10(9) cells). In addition, the "treatment-free period" was also significantly (P less than 0.025) shorter in the group of atypical B-CLL compared with the typical B-CLL group. No clear-cut statistical differences in lymphocyte surface markers or in several other prognostic factors between the two subgroups of B-CLL were found. The present study supports the idea that in B-CLL the simultaneous determination of ADA, PNP, and LDH might be helpful in better understanding the pathophysiology, prognosis, and natural history of the disease.     

急性淋巴细胞白血病患儿T淋巴细胞免疫功能的研究

目的　研究急性淋巴细胞白血病 ( AL L )患儿初治时和完全缓解 ( CR)后外周血 T淋巴细胞亚群数量及其功能 ,寻找更好的控制儿童白血病的方法。方法　采用单克隆抗体在流式细胞仪上测定了 18例 B淋巴细胞系 AL L 儿童初治时、CR后外周血单个核细胞 ( MNC) CD3、CD4、CD8以及 IL-2受体 ( CD2 5 )含量及其 T淋巴细胞内细胞因子 γ-干扰素 ( IFN-γ)和肿瘤坏死因子 -α( TNF-α)水平。结果　初治时患儿 CD4/ CD8为 ( 1.10± 0 .79) ,较健康儿童 [( 2 .74± 1.2 1) ]明显降低 ( P<0 .0 1) ;CD4、CD8产生细胞因子的能力 ( IFN-γ和 TNF-α水平 )均低于正常儿童 ( P<0 .0 5)。 CR后 ,CD4/ CD8为 ( 2 .54± 1.3 9) ,比初治时明显提高 ( P<0 .0 5) ,CD4、CD8产生细胞因子的能力增强 ,但与正常对照组比较 ,各项数值仍低。初治患儿 CD4T淋巴细胞中 CD2 5 细胞数量为 ( 0 .76± 0 .56) ,明显低于 CR患儿 [( 2 0 .4± 5.1) ]和对照组 [( 16.3± 6.3 ) ] ,P均 <0 .0 1。结论　免疫损害在白血病的发病过程中起重要作用 ;T淋巴细胞的免疫功能与儿童白血病的预后关系密切 ;促进患儿免疫功能的恢复对治疗有重要意义     

Recent progress in acute leukemia and myelodysplasia

The advances and progress in the understanding and management of acute leukemia and myelodysplasia continue to occur at an exponential rate. While this has led to more therapy options, clinicians and researchers are now facing more challenges in terms of clinical decision-making and more unanswered questions. This paper has outlined some conundrums in acute leukemia and myelodysplasia, and the efforts that are underway to address these.     

Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.     

急性髓性白血病患者血清胆固醇水平变化与低密度脂蛋白受体活性的关系研究

测定了52例初发未急性髓性白血病（AML）患者血清胆固醇浓度及外周血白血病细胞对^125I-低密度脂蛋白（^125I-LDL)的降解率,结果显示两者呈负相关,白细胞及^125I-LDL降解率较高者血清胆固醇浓度较低,化疗后,随着外周血白血病细胞消失,血清胆固醇及LDL胆固醇水平升高。据此推测AML患者的低胆固醇血症可能归因子白血病细胞的LDL受体活性增高,白血病细胞对LDL的高摄取及降解为利用LDL作为化疗药物的载体靶向治疗白血病提供了新思路。     

The role of colony-stimulating factors in acute leukemia

Summary This article summarises the effects of colony-stimulating factors and related molecules on leukemia blasts by focussing on autocrine and paracrine growth control. This information may lead to a better understanding of the pathobiology of this highly malignant disorder, and may have therapeutic implications.Abbreviations used GM-, G-, M-CSF granulocyte-macrophage, granulocyte and macrophage colony-stimulating factors - IL interleukin - AML-CFU acute myelogenous leukemia colony-forming unit - HGF hematopoietic growth factor The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.     

急性白血病膜Fas及sFas的表达及其与疗效关系

目的探讨急性白血病膜Fas(mFas)及血清可溶性Fas(sFas)表达的意义。方法应用免疫组化SABC法和双抗夹心酶联免疫吸附试验法(ELISA),于2001-112002-09对滨州医学院附属医院的30例急性白血病患者检测骨髓细胞mFas抗原及血清sFas的表达,与正常对照组比较,并分析sFas与治疗效果的关系。结果骨髓细胞mFas抗原阳性表达率在急性淋巴细胞白血病(ALL)为(5·62±2·27)%,急性非淋巴细胞白血病(ANLL)为(8·80±4·15)%,均低于正常对照组(28·75±11·20)%(P<0·01);化疗前血清sFas在ALL为(7·92±2·36)μg/L,ANLL为(8·79±3·12)μg/L,均高于正常对照组;CR组化疗后血清sFas[(4·08±2·24)μg/L]较化疗前[(7·85±1·96)μg/L]显著降低(P<0·01)。结论mFas下调及血清sFas升高所致的Fas/FasL凋亡途径障碍可能参与急性白血病的发病,血清sFas可作为急性白血病观察疗效、判断预后的参考指标。     

Current issues in the management of acute promyelocytic leukemia

trans retinoic acid (ATRA), both PML-dependent apoptotic mechanisms and myeloid-specific gene expression programs are reactivated. In the clinic, the combination of anthracycline-based chemotherapy plus ATRA cures approximately 80% of APL patients, and a high percentage of relapsed patients can achieve second remissions with arsenic trioxide. With the publication of results from the European APL 93 trial, the ‘standard-of-care’ for induction treatment of APL now includes ATRA plus concurrent anthracycline-based chemotherapy. The amount and type of consolidation therapy necessary for an individual APL patient remains somewhat of an open question, but at present should include at least two cycles of chemotherapy. Based on recent trials that demonstrate a benefit of maintenance ATRA ( ± low-dose chemotherapy), all APL patients should probably receive some type of maintenance therapy. While the above approach currently cures the majority of APL patients, future improvements in the treatment of this disease will require risk-adapted protocols that incorporate real-time molecular monitoring and appropriate introduction of novel therapeutic agents. Received: 19 August 1999 / Accepted: 9 November 1999     

急性白血病止凝血异常的预后意义

目的：探讨急性白血病（AL）患者的止凝血异常及其与预后的关系。方法：运用ELISA或发色底物法对56例AL患者血浆一系列止凝血指标进行了检测。结果：治疗前血浆血栓调节蛋白（TM）、P－选择素、可溶性纤维蛋白单体复合物（SFMC）、组织纤溶酶原激活性（t－PA）、D－二聚体水平显著升高,蛋白C抗原（PC：Ag）、纤溶酶原激活抑制物（PAI）水平低于正常,纤维蛋白原（Fg)、蛋白C活性（PC：A）、蛋白S水平（PS）与正常对照组差异无显著性意义,治疗后除蛋白C活性外均恢复至正常范围内;治疗前后TM升高、治疗前PS降低及PAI升高者预后较差,其中治疗后TM和治疗前PAI是决定患者无复归生存时间的预后因素,治疗后TM、治疗前PS和PAI水平是决定患者总生存时间的预后因素。结论：AL发病过程中存在血管内皮细胞损伤、血小板活化以及凝血、抗凝、纤溶系统的激活,并随病情的好转而逐渐改善;血管内皮损伤、PS消耗及纤溶抑制活性增强与患者的预后密切相关。     

小儿急性淋巴细胞白血病转铁蛋白受体表达的临床研究

采用 APAAP桥联酶标技术测定 5 1例急性淋巴细胞白血病 (AL L )初发患儿、4 0例完全缓解 (CR)患儿、10例复发患儿外周血单个核细胞 (PMNCs)上转铁蛋白受体 (Tf R)的表达水平。发现 AL L各期 (初发、CR、复发 ) Tf R表达水平均比正常对照组明显增加 (P均 <0 .0 0 1) ;4 0例 CR患儿的 Tf R水平较其初发时显著降低 (P<0 .0 0 1) ;10例复发患儿 Tf R水平较其 CR时显著升高 (P<0 .0 1) ;13例高危型 AL L 患儿的 Tf R水平明显高于 38例普通型 AL L 患儿 (P<0 .0 5 )。提示 AL L患儿 PMNCs上 Tf R表达水平对估计病情、观察疗效、判断预后具有一定意义     

急性白血病细胞HCP基因的突变分析

目的：造血细胞磷酸酶(Hematopoietic cell phosphatase，HCP)在造血细胞发育、增殖及受体介导的有丝分裂信号传导通路中发挥关键的负调节作用，在motheaten小鼠中其突变可导致粒一单核细胞严重的过度聚积和功能紊乱。本研究旨在评价HCP基因突变在急性白血病发病中的作用。方法：利用RT—PCR、SSCP及DNA序列分析技术检测了41例急性白血病、8株白血病细胞系及50例正常对照骨髓或外周血标本中HCP基因表达及突变情况。结果：RT—PCR显示所有标本中都有HCP基因表达，仅在1例急性淋巴细胞白血病细胞中发现错义突变，发生在HCP基因氨基末端的SH2结构域；此外，分别在HCP基因的69、85、86和266密码子存在多态性。结论：HCP基因突变在急性白血病中较少见，在白血病发病中可能起较小作用。     

Flow cytometry study of cell cycle, apoptosis and drug resistance in acute leukemia

The response to therapy of leukemic cells is largely determined by their capacity of proliferation and apoptosis in presence of the administered drugs. We describe here the main markers used in flow cytometry (FCM) and involved in the assessment of cell cycle parameters: single labeling by Propidium Iodide (PI) and double labeling anti-Bromodeoxyuridine (BrdUrd)/PI which, both in vitro and in vivo, gives cell percentages in the different cell cycle phases. The markers of cell cycle progression can be divided into proliferation markers such as PCNA (proliferating cell nuclear antigen) or Ki-67 and cell cycle progression markers. The latter, which are the core of the cell cycle machinery, are molecules recently characterized (Cyclins, CDKs (cell dependent kinases), CDIs (cyclin-dependent kinase inhibitors)) and their cell expression can be analyzed using FCM. FCM is also one of the best means to detect and quantitate appoptotic cells. Several techniques are described: Nuclear labeling using Hoechst 33342: mitochondrial labeling using DiOC6(3): detection of DNA fragmentation using 1) labeling of fixed and permeabilized cells with a DNA marker or 2) labeling of the free 3 DNA ends using incorporation of labeled deoxynucleotides; detection of antigens in apoptotic cells (Bcl-2, Fas, phospholipids...). At last, we analyzed flow cytometry methods to study the cell resistance to Ara-C and anthracyclins. In combination with cell kinetic studies and detection of apoptotic cells, they should increase the efficiancy of the acute leukemia treatment.     

急性白血病患者端粒酶催化亚单位和p16基因表达与端粒酶活性的关系

目的 :探讨端粒酶催化亚单位 (hTERT)和p 16基因表达与端粒酶活性的关系及其在急性白血病发生过程中的作用。方法 :采用TRAP和RT PCR法分别检测 5 2例急性白血病患者 (白血病组 )及 2 0例非白血病且骨髓象正常者 (对照组 )的端粒酶活性与hTERTmRNA表达。用免疫细胞化学SP法测定上述对象的P 16蛋白表达。结果 :白血病组端粒酶活性与hTERTmRNA的阳性率分别为 75 .0 %和 80 .8%,而对照组均为阴性。白血病组hTERTmRNA表达与端粒酶活性呈显著正相关 (r =0 .6 5 ,P <0 .0 1)。白血病组及对照组P 16蛋白阳性表达率分别为 34 .6 %和 95 .0 %,二者比较差异有非常显著性意义 (P <0 .0 1)。白血病组P 16蛋白表达与端粒酶活性呈显著负相关 (r =- 0 .81,P <0 .0 1)。结论 :hTERTmRNA表达和p 16基因失活可能在急性白血病发生发展过程中有一定作用 ,急性白血病细胞端粒酶激活可能与hTERTmRNA表达及p 16基因失活有关。     

C-reactive protein and lactate dehydrogenase isoenzymes in the assessment of the prognosis of acute pancreatitis

The value of serum C-reactive protein, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate in predicting the outcome of acute pancreatitis was evaluated for 57 episodes in 54 patients. Serum C-reactive protein levels on day 2, 4 and 7 after admission were significantly higher in 19 episodes of severe attacks than in 38 episodes of mild attacks (13.71 +/- 9.68, 9.00 +/- 7.54, 6.02 +/- 3.83 vs 4.78 +/- 3.91, 3.30 +/- 3.61, 1.43 +/- 2.08 mg/dL; P less than 0.0001, P less than 0.005, P less than 0.0001, respectively). The sensitivity, specificity and accuracy of predicting a severe attack were 94, 76 and 82% using C-reactive protein greater than or equal to 8 mg/dL on day 2; 67, 92 and 84% using C-reactive protein greater than or equal to 5 mg/dL on day 7; and 59, 76 and 70% using Ranson's criteria greater than or equal to 3. Increases in LDH-4 and LDH-5 isoenzymes were found in both groups, with LDH-4 being slightly higher in severe attacks than in mild attacks. There was no significant difference of erythrocyte sedimentation rate between both groups. When compared with Ranson's criteria, lactate dehydrogenase isoenzymes and erythrocyte sedimentation rate, C-reactive protein is more valuable in the early assessment of the severity of acute pancreatitis.     

Characteristics of fibrinolytic disorders in acute promyelocytic leukemia

ABSTRACT

Objectives: Catastrophic hemorrhage remains the main cause of acute promyelocytic leukemia (APL) treatment failure. This study was aimed to study the pathogenesis of coagulopathy in patients with APL.

Methods: Multiple procoagulant and profibrinolytic parameters in plasma and peripheral leukocytes from 24 patients with newly diagnosed APL accompanied by coagulopathy before and after arsenic trioxide (ATO) treatment were evaluated.

Results: Prior to the treatment, the patients had elevated D-dimer and decreased fibrinogen levels. Plasma urokinase-type plasminogen activator receptor (uPAR) and plasmin–ɑ₂ antiplasmin complexes (PAP) levels, plasmin (Pn) activity, and cell surface levels of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) were significantly higher; plasma plasminogen activator inhibitor-1 (PAI-1) levels and plasminogen (Pg) activity were significantly decreased; plasma plasminogen activator (PA) activity, uPA and tPA levels; and cell surface levels of uPAR and annexin II were not significantly different from levels in the control group. During ATO treatment, both patients’ plasma PA activity and uPAR on leukocytes gradually increased, annexin II on leukocytes increased initially and decreased afterwards, and tPA and uPA on leukocytes remained consistently higher in the patients than in the controls. Other parameters gradually tended toward normal values.

Conclusions: In APL, activated coagulation system activated fibrinolytic system, and increased uPAR levels could contribute to the hyperfibrinolysis. Annexin II might not be involved in the coagulopathy.     

运动疗法改善急性白血病化疗患者疲劳状况的研究

目的探讨运动疗法对急性白血病患者化疗后疲劳的影响。方法将120例急性白血病患者随机分为实验组和对照组,实验组采用运动疗法干预措施,对照组不采用干预措施。结果实验组疲劳程度及骨髓抑制程度低于对照组,差异有统计学意义（P〈0.05）。结论运动疗法可降低急性白血病患者化疗后疲劳的程度。     

Expression and functional activity of P-glycoprotein in adult acute myelogenous leukemia patients

 Expression and functional activity of P-glycoprotein (P-gp) were measured in 182 acute myelogenous leukemia (AML) patients: 136 patients were treated with the AML-6 protocol (EORTC), containing daunorubicin, vincristine, and conventional-dose cytarabine (ara-C), and 21 patients received idarubicin, vepeside, and conventional-dose ara-C (ICE-AML-10 protocol/EORTC). An additional 25 patients were treated with a dose of idarubicin and ara-C, modified as compared with the ICE protocol, but with the same dose of etopside (ICE-I protocol). P-gp was determined using monoclonal antibody 4E3.16 and functional activity using the rhodamine 123 accumulation test. P-gp positivity was defined as a Kolmogorov Smirnov (KS) D value ≥0.15, P-gp negativity as a KS D value <0.15. P-gp activity was defined as a ratio of mean rhodamine 123 accumulation with/without verapamil. In AML patients at primary diagnosis and early relapse/refractoriness a significant (p<0.05) difference between P-gp-positive and P-gp-negative patients was ascertained using the AML-6 protocol; the difference corresponded to the complete remission rate. For ICE- and ICE-I-treated AML patients at primary diagnosis this significance was not shown. Compared with AML patients at primary diagnosis and patients at early relapse or refractoriness, a significantly (p<0.05) increased incidence of non-pumping P-gp and a trend (p=0.054) to a higher percentage of non-P-gp-related mechanisms in AML patients at late relapse was determined. When the AML-6 protocol is used, age, activated P-gp, and CD34 expression are independent prognostic factors in AML patients. A test system which determines a functional P-gp overexpression is a major tool for identifying a group of AML patients with a poor prognosis. In order to effectively use so-called P-gp modulator substances, the degree of P-gp expression, the activated or nonactivated P-gp condition, and detection of non-P-gp-related resistance mechanisms are of utmost interest for optimal design and analysis of P-gp modulator trials and for understanding the complexity of chemotherapy-related resistance mechanisms in patients. Received: 26 March 1997/Accepted: 10 June 1997     

急性早幼粒细胞白血病患者早期死亡原因探讨

目的 :探讨急性早幼粒细胞白血病 (APL)患者早期死亡原因。方法 :分析 12例早期死亡患者的临床资料。结果 :12例患者中 ,8例外周血白细胞大于 4 0× 10 9/L ,全部患者均检获t(15 ;17)及PML/RARα 基因 ,8例PML/RARα 基因为S型 ;9例死于DIC ,3例死亡与纤溶有关。结论 :具有高细胞负荷 ,FAB亚型为M3 b ,PML/RARα 基因为S型 ,未经ATRA诱导分化即开始联合化疗的APL易于早期死亡 ;并与DIC的发生和纤溶亢进有关。     

Sequentisl induction chemotherapy with vincristine,daunorubicin cyclophosphamide,and prednisone in adult acute lymphoblastic leukemia

Sequential chemotherapy with vincristine, daunorubicin, cyclophosphamide, and prednisone doses was administered to 57 adult patients with acute lymphoblastic leukemia (ALL). Complete remission (CR) was achieved in 51 (89%, 95% confidence intervals, [CI] 78–96%). Among patients achieving CR, 62% were in CR after one sequence of chemotherapy, 23% after two sequences, and 5% after three sequences. Six patients (11%) had resistant disease. All patients experienced profound myelosuppression. Median time to recovery of neutrophils > 0.5 × 10⁹/l was 22 days (range: 5–89 days), and of platelets >100×l0⁹/l 21 days (range: 0–45 days). Nonhematologic WHO grade 3 or more side effects consisted predominantly of hyperbilirubinemia (7%), mucositis (5%), nausea and vomiting (2%), and cutaneous toxicity (1%). Severe infectious complications occurred in only 14% of cases. One patient (2%, 95% CI 0–9%) died of therapy-related toxicity while in early CR. We concluded that sequential use of prednisone seemed at least as effective as continuous administration at the expense of a few adverse side effects.