Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Asparaginase ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Drug Administration Routes ; Drug Administration Schedule ; Forecasting ; Humans ; Leukemia ; drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

OBJECTIVETo investigate the safety and therapeutic effect of low dose (1000 U/m(2)) L-asparaginase (L-Asp) in the treatment of children with acute lymphoblastic leukemia (ALL).

METHODSSix patients were treated with low dose L-Asp after previously suffered severe side effects from standard dose L-Asp (5000 - 10,000 U/m(2)). Twenty-eight blood samples were obtained randomly from 5 of them. Plasma asparagine concentration was detected by reverse phase-high performance liquid chromatography (RP-HPLC).

RESULTSAll the patients treated with low dose L-Asp showed no any toxic symptoms. The plasma asparagine levels in the patients were all above 5 micromol/L except case 4 (4.91 micromol/L) before receiving L-Asp, and were all decreased below 0.5 micromol/L five days after receiving low dose L-Asp, except case 3 (3.70 micromol/L), the results being like that of receiving standard dose L-Asp.

CONCLUSIONLow dose L-Asp has definite efficacy for childhood ALL, while avoids serious side effects from standard dose L-Asp.

Adolescent ; Antineoplastic Agents ; administration & dosage ; adverse effects ; blood ; Asparaginase ; administration & dosage ; adverse effects ; blood ; Child ; Child, Preschool ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Treatment Outcome

OBJECTIVETo investigate the changes in the activity of Escherichia coli asparaginase (L-asp) and the concentration of asparagines (ASN) in the plasma of the acute lymphoblastic leukemia (ALL) children receiving L-asp containing chemotherapeutic protocol to explore more reasonable usage of L-asp in the treatment of childhood ALL.

METHODSL-asp containing hemotherapy regimen of VDLP was used, in which L-asp (10,000 U/m(2)) was administered intravenously every other day for 10 doses in 15 children with ALL. A total of 340 peripheral blood samples were collected at scheduled time points during the therapy and plasma L-asp activity (by spectrophotometric assay) and asparagines concentration (by RP-HPLC) were measured.

RESULTSDuring the administration of L-asp, the plasma L-asp activity was increasing gradually peaked after eight doses and then decreased gradually, while the plasma concentration of asparagines maintained in complete or nearly complete depletion status. After the therapy courses finished, a plasma L-asp activity above 100 U/L with asparagines almost complete depletion status was lasting for about seven days.

CONCLUSIONThe current L-asp containing chemotherapeutic protocols in which L-asp was administered in a dose of 10 000/m(2) intravenously every other day, are efficient enough for the depletion of plasma ASN.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; blood ; pharmacokinetics ; therapeutic use ; Asparaginase ; administration & dosage ; blood ; pharmacokinetics ; Asparagine ; blood ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Humans ; Infusions, Intravenous ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Treatment Outcome

This study was purposed to investigate the possible side effects of L-asparaginase (L-ASP) in the treatment of patients with acute lymphoblastic leukemia (ALL) and to explore the correlation of these side effects at different therapeutic stages by means of retrospective analysis, so as to reduce the incidence of side effects and improve the safety of chemotherapy and the long-term survival of patients. The probability and severity of side effects related to use of L-ASP in 38 cases of ALL during remission induction therapy (VDLDex regimen) and 40 cases of ALL during maintenance intensive therapy (VMLDex regimen) were compared. The results showed that allergic response, diabetes and drug-induced liver disease happened more frequently during maintenance therapy than during remission induction therapy, while defibrination, abnormal hemagglutinin, acute pancreatitis, hypoproteinemia, gastrointestinal reaction and infectious shock were observed more during remission induction therapy than those at maintenance therapy. In conclusion, the L-ASP showed some side effects especially for the patients during the remission induction therapy which should be paid enough attention. The regular and comprehensive monitoring can effectively reduce and avoid the side effects of L-ASP, to improve the safety of chemotherapy.
Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Asparaginase ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Remission Induction ; Treatment Outcome

OBJECTIVETo investigate the H2O2-induced expression of human histone acetyltransferase-like protein (hALP), a telomerase regulation-associated gene, and its effects on the stress-triggered cellular senescence.

METHODSThe induced expression of hALP was measured by semi-quantitative RT-PCR and immunofluorescent histochemistry after treatment of HeLa cells by H2O2. The effects of hALP expression on cellular responses to H2O2 were analyzed by MTT, flowcytometry, and SA-beta-gal staining, respectively.

RESULTShALP mRNA could be dose-dependently induced by treatments of 0.2-1.6 mmol/L H2O2, and the induction could be observed after 6 hours and kept for 36 hours in the presence of 0.4 mmol/L H2O2. Meanwhile, the immunofluorescent staining showed marked stronger nuclear intensity of hALP protein in H2O2-treated HeLa cells. In the treatment of H2O2, the ectopic expression of hALP enhanced continuous growth and overcame G2/M arrest as well as decreased senescence-associated beta-gal staining. On the contrary, the transfected clones with antisense or blank vector and original He-La cells presented growth suppression, G2/M delay and higher percentage of SA-beta-gal activities in the presence of H2O2.

CONCLUSIONSThe expression of hALP could be up-regulated by treatment of H2O2, and elevated expression could enhance cellular resistance to H2O2-induced cellular senescence. The data might be of references to elucidation of basic biological function of hALP gene and its associated telomerase activity.

Asparaginase ; biosynthesis ; genetics ; Autoantigens ; biosynthesis ; genetics ; Cell Cycle ; Cell Proliferation ; Cellular Senescence ; drug effects ; Dose-Response Relationship, Drug ; HeLa Cells ; Humans ; Hydrogen Peroxide ; administration & dosage ; pharmacology ; Oxidants ; administration & dosage ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Transfection ; Up-Regulation

OBJECTIVETo analyze the short-term efficacy, overall survival (OS), and safety in newly diagnosed extranodal NK/T-cell lymphoma (ENKTL) patients with L-asparaginase based regimens or CHOP regimen in combination with radiotherapy as first-line treatment.

METHODSOf the total 181 patients diagnosed by imaging and pathology, 69 patients received CHOP regimen and 112 patients received L-asparaginase based regimens. All the patients received radical radiotherapy(RT)after 6 cycles of chemotherapy.

RESULTSThe overall response rates of L-asparaginase-based group and CHOP group were 90.2% and 72.5%, respectively (P=0.002). The 1, 2, 5-year OS and progression-free survival (PFS) in L-asparaginase-based group were 96.0%, 88.3%, 65.1% and 94.2%, 79.8%, 50.0%, respectively. The 1, 2, 5-year OS and PFS in CHOP group were 82.6%, 61.9%, 28.4% and 63.8%, 44.0%, 21.0% (P=0.000).

CONCLUSIONCompared with CHOP regimen, L-asparaginase-based chemotherapy is more effective and safe for newly diagnosed nasal-type ENKTL.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asparaginase ; administration & dosage ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Humans ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Vincristine ; therapeutic use

OBJECTIVETo observe the efficacy of polyethylene glycol conjugated asparaginase (peg-asp) for induction treatment of children with newly diagnosed acute lymphoblastic leukemia (ALL).

METHODA total of 268 newly diagnosed children with ALL enrolled in CCLG-2008 from January, 2010 to August, 2012 were analyzed. Patients received either native Escherichia coli asparaginase or pegaspargase along with multiagent chemotherapy during remission induction treatment. Status of bone marrow aspiration was assessed on day 15, day 33 (M1, M2, M3).

RESULTOf the 268 patients stratified, 37.3% (n = 100) were SR, 32.1% (n = 86) were IR, and 31.6% (n = 82) were HR; 159 patients received native Escherichia coli asparaginase and 109 patients received pegaspargase. Characteristics of two groups in age, sex, blood count at diagnosis, immunophenotype and response to prednisolone had no significant difference (P > 0.05). Bone marrow status on day 15 in pegaspargase group was M1 in 70 (64.2%) cases, M2 in 23 (21.1%) and M3 in 16 (14.7%), while in native Escherichia coli asparaginase group, M1 in 112 (70.4%) cases, M2 in 21 (13.2%) and M3 in 26 (16.4%), respectively (χ(2) = 2.938, P = 0.230). Bone marrow status on day 33 was M1 in 105 (96.3%), M2 in 3 (2.8%) and M3 in 1 (0.9%) in pegaspargase group, while it was M1 in 154 (96.9%) cases, M2 in 5 (3.1%) and M3 in native Escherichia coli asparaginase group, respectively (χ(2) = 1.494, P = 0.474).

CONCLUSIONDomestic pegaspargase of our country can achieve the similar efficacy in induction treatment for ALL patients as compared with native Escherichia coli asparaginase. The drug could be considered as not only the choice for allergic patients but also a first-line alternative for new patients.

Adolescent ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asparaginase ; administration & dosage ; adverse effects ; Bone Marrow Cells ; drug effects ; pathology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Polyethylene Glycols ; administration & dosage ; adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; pathology ; Prednisone ; administration & dosage ; adverse effects ; Remission Induction ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Because of the relative paucity of data regarding the clinical outcome in adult patients with acute lymphocytic leukemia (ALL) in Korea, we analyzed clinical courses in adult ALL patients treated with VPD (L) regimen (vincristine, prednisolone, daunorubicin, L-asparaginase) at the Seoul National University Hospital, and evaluated prognostic factors influencing the outcome. METHODS: Patients with ALL newly diagnosed between October 1994 and June 2000 at our hospital were analyzed retrospectively. Fifty-three patients were evaluable. Induction chemotherapy consisted of VPD with (46 cases) or without L-asparaginase (7 cases). After complete remission (CR), consolidation therapy, CNS prophylaxis and maintenance chemotherapy were administered. RESULTS: Ages ranged from 16 to 67 (median 30). CR rate was 86.8% (46/53) and no significant prognostic factor was found for the CR rate. With a median follow-up time of 27.2 months (range 12.9~83.0 months) in living patients, the median overall survival (OS) for all cases was 16.7 months (13.4~20.1 months, 95% C.I.) and the estimated 4-year OS rate was 25.4%+/-8.9%. The median relapse-free survival (RFS) was 12.2 months (8.4~16.0 months, 95% C.I.), and 3-year RFS rate was 29.9%+/-10.2%. Poor prognostic factors for OS were Ph chromosome (p=0.005) and T-cell immunophenotype (p=0.03). For RFS they were Ph chromosome (p=0.01) and the presence of a mediastinal mass (p=0.03). CONCLUSION: Despite an initial excellent response to the VPD (L) regimen, newer therapeutic strategies, including more intensive postremission therapies, are urgently needed because of the high relapse rate. Future therapeutic approaches need to be stratified according to several prognostic factors.
Administration, Oral ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects ; Asparaginase/*administration & dosage/adverse effects ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Doxorubicin/*administration & dosage/adverse effects ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Male ; Maximum Tolerated Dose ; Middle Aged ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*drug therapy/*mortality ; Prednisone/*administration & dosage/adverse effects ; Probability ; Remission Induction ; Retrospective Studies ; Survival Analysis ; Treatment Outcome ; Vincristine/*administration & dosage/adverse effects

OBJECTIVETo confirm the responses and function of hALP, a telomerase-regulation associated gene, in DNA damage.

METHODSHeLa and Hep2 cells were treated by genotoxic agents H2O2 and cisplatin, and the induced expression of hALP was measured by quantitative RT-PCR and immunofluorescent histochemistry. The alterations in transcriptional activity of hALP promoter were estimated by luciferase reporter assays. The effects of genotoxic agents on cells in different status of hALP expression were analyzed by MTT method.

RESULTSThe level of hALP mRNA could be increased when treated by 0.2 - 1.6 mmol/L H2O2 and reach a peak in concentration of 0.4 mmol/L. The induction could be observed after 6 h in the treatment of 0.4 mmol/L H2O2 and the higher level can be retained for 36 h. Similarly, cisplatin induced hALP mRNA expression is also dose and time dependent. The immunofluorescent staining showed that the treatment of 0.2 or 0.4 mmol/L H2O2, 0.2 or 0.5 micromol/L cisplatin increased the intensity of hALP protein in cellular nuclei. The luciferase assays demonstrated that both H2O2 and cisplatin could up-regulate hALP promoter activity through its upstream - 705 - +20 nt region. In cell survivor assay, the HeLa cells expressing sense hALP gene could grow continuously in the presence of 0.4 mmol/L H2O2 or 0. 5 micromol/L cisplatin while cells with antisense hALP or control cells were slower in growth.

CONCLUSIONSThe expression of hALP gene could be up-regulated by DNA damage through activating transcription of its promoter, and increase cellular resistance to genotoxic agents.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Asparaginase ; biosynthesis ; genetics ; Autoantigens ; biosynthesis ; genetics ; Cell Proliferation ; Cells, Cultured ; Cisplatin ; administration & dosage ; pharmacology ; DNA Damage ; physiology ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Enzymologic ; HeLa Cells ; metabolism ; Humans ; Hydrogen Peroxide ; administration & dosage ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Telomerase ; genetics ; physiology ; Up-Regulation

Antineoplastic Agents ; administration & dosage ; adverse effects ; Asparaginase ; administration & dosage ; adverse effects ; Child ; Child, Preschool ; Combined Modality Therapy ; Dose-Response Relationship, Drug ; Drug Hypersensitivity ; prevention & control ; Female ; Humans ; Hyperglycemia ; chemically induced ; prevention & control ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Severity of Illness Index ; Time Factors ; Treatment Outcome