Comparative pharmacokinetic studies of three asparaginase preparations.

PURPOSE As part of pharmacologic studies of asparaginase (ASNase), we determined the half-life of ASNase activity and protein, and the effect of dose, repeated doses, different drug preparations, and hypersensitivity reactions on the half-life (t1/2) of serum ASNase activity. PATIENTS AND METHODS We measured ASNase activity (spectrophotometric assay) in serum samples obtained from patients with acute lymphoblastic leukemia (ALL) at various times during their therapy with intramuscular ASNase. ASNase protein was measured by enzyme-linked immunoadsorbent assay (ELISA). RESULTS Studies following the initial dose of Escherichia coli-derived ASNase demonstrated no difference in apparent t1/2 following 25,000 IU/m2 versus 2,500 IU/m2 (1.24 v 1.35 days, P = .2). The apparent t1/2s following maintenance doses of E coli ASNase (middle dose t1/2, 1.28 days, or last dose t1/2, 1.14 days) showed no difference when compared with the initial dose of ASNase (P = .3 to .9). There was no significant difference between the apparent t1/2s of ASNase activity and ASNase protein (n = 8, P = .2 to .6). The serum t1/2 was 0.65 and 5.73 days for patients receiving Erwinia or polyethylene glycol (PEG)-modified E coli ASNase, respectively, as the induction dose. ASNase activity was undetectable in sera of four patients studied in the week following an anaphylactic reaction to E coli ASNase and the t1/2 was significantly shorter in five patients with a history of allergic reaction to E coli ASNase who were studied following a dose of PEG ASNase, (t1/2, 1.80 days). CONCLUSION We conclude that (1) the apparent t1/2 of ASNase is dependent on enzyme preparation used, but is not affected by dose or by repeated use; (2) the apparent t1/2 of E coli ASNase as a protein is the same as the apparent t1/2 of enzymatic activity; and (3) patients who have had a hypersensitivity reaction to E coli ASNase have a decreased apparent t1/2 with both E coli and PEG ASNase.

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Randomized Comparison of IV PEG and IM E. Coli Asparaginase in Children and Adolescents with Acute Lymphoblastic Leukemia: Results of the DFCI ALL Consortium Protocol 05-01

Blood ◽

10.1182/blood.v118.21.874.874 ◽

2011 ◽

Vol 118 (21) ◽

pp. 874-874 ◽

Cited By ~ 2

Author(s):

Lewis B. Silverman ◽

Kristen Stevenson ◽

Lynda M Vrooman ◽

Jeffrey G Supko ◽

Barbara Asselin ◽

...

Keyword(s):

Enzyme Activity ◽

Children And Adolescents ◽

Lymphoblastic Leukemia ◽

Age Groups ◽

Serum Samples ◽

Childhood All ◽

E Coli ◽

Significant Difference ◽

Consolidation Phase

Abstract Abstract 874 E. coli L-asparaginase (E. coli ASP) is an important component of treatment for childhood ALL, but is associated with multiple toxicities, including allergy, pancreatitis, and thrombosis. It is typically given intramuscularly (IM). Because most pediatric ALL patients have indwelling venous catheters, intravenous (IV) administration of asparaginase would be a more convenient and less painful option than IM injection. PEG-asparaginase (PEG), the polyethylene glycol conjugate of E. coli ASP, has a longer circulating half-life and so may be given less frequently. We have previously demonstrated that a single dose of PEG 2500 IU/m2 given IV is tolerable in children with ALL, with potentially therapeutic serum enzyme activity (≥ 0.1 IU/mL) maintained for at least 18 days in most patients.[Blood 2010;115:1351-3] On DFCI ALL Consortium Protocol 05-01, all patients (pts) with newly diagnosed ALL aged 1–18 years (yrs) who achieved complete remission were eligible to participate in a randomized comparison of IM E. coli ASP and IV PEG during the 30-week (wk) multi-agent post-induction Consolidation phase. Beginning at week 7 of therapy, pts received either IM E. Coli ASP 25000 IU/m2 weekly × 30 wks or IV PEG 2500 IU/m2 every 2 wks × 30 wks. Serum samples were obtained every 6 wks just prior to an ASP dose and were assayed for ASP enzyme activity by a validated biochemical assay. Between 2005–2010, 463 pts were enrolled in the randomized comparison. Median age was 5 yrs (range 1.2–17.9 yrs). There was no significant difference in presenting characteristics between the two arms, except that more pts on the E. coli ASP arm presented with a mediastinal mass (9% vs 3%, p=0.04). Median follow-up was 2.8 years. Median nadir serum ASP activity (NSAA) at each assayed timepoint during the Consolidation phase was significantly higher with IV PEG than with IM E. coli ASP (Table 1). An NSAA of ≥ 0.1 IU/mL was achieved in ≥ 95% of IV PEG pts compared with < 50% of IM E. coli ASP pts (p<0.01 at each timepoint). There was no significant difference in ASP-related toxicities (allergy, pancreatitis, thrombosis) between the two types of ASP (Table 2). Older pts (≥ 10 yrs old) had a significantly higher overall rate (p<0.01) of pancreatitis (18% vs 7%) and thrombosis (18% vs 4%), but not of allergy (p=0.49) or infection (p=0.21), compared to younger pts. There was no significant difference in the rates of ASP-related toxicities when comparing IM E. coli ASP vs IV PEG separately within the two age groups (≥10 yrs and < 10 yrs). We conclude that every 2-week IV PEG is no more toxic than weekly IM E. coli ASP in children and adolescents with ALL, and is associated with higher serum ASP activity. Longer follow-up is necessary to determine whether there is any difference in event-free survival between the two treatment arms.Table 1:Nadir Serum ASP activity (NSAA) during 30-week Consolidation phaseIV PEGIM ECOLISample Time (wks)*NMedian IU/mL% pts with NSAA ≧ 0.10 IU/mLNMedian IU/mL% pts with NSAA ≧ 0.10 IU/mL5840.6795%920.09448%11700.7197%740.09447%17730.7697%860.09247%23600.70100%760.09446%29680.70100%630.09544%*Number of weeks after start of Consolidation phaseTable 2:Toxicities by ASP type during 30-week Consolidation phaseToxicityIV PEG # of pts (%)IM E. COLI # of pts (%)p-valueNumber of Patients232231Asparaginase Toxicity59 (25)58 (25)>0.99 Allergy26 (11)20 (9)0.44 Pancreatitis25 (11)21 (9)0.64 Mild/Moderate13 (6)13 (6) Severe12 (5)8 (3) Thrombosis14 (6)21 (9)0.22Infection (bacteremia, invasive fungal disease)35 (15)46 (20)0.18 Disclosures: Silverman: Enzon Pharmaceuticals: Honoraria. Supko:Enzon Pharmaceuticals: Research Funding. Sallan:Enzon Pharmaceuticals: Honoraria.

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Serological Investigations of Brucellosis in Cattle, Farmers and Veterinarians in the Kars District of Turkey

Acta Veterinaria Brno ◽

10.2754/avb200877010117 ◽

2008 ◽

Vol 77 (1) ◽

pp. 117-121 ◽

Cited By ~ 7

Author(s):

S. Otlu ◽

M. Sahin ◽

H. I. Atabay ◽

A. Unver

Keyword(s):

Control Measures ◽

Serum Samples ◽

Serological Tests ◽

Significant Difference ◽

High Prevalence ◽

History Of ◽

And Control

The prevalence of brucellosis was investigated in cattle, farmers and veterinarians in the Kars district of Turkey between 2004 - 2006. In order to achieve this, a total of 407 serum samples of cattle from 27 herds having history of abortions were examined for Brucella antibodies by RBPT and SAT. In addition, the sera collected from 246 farmers (130 males and 116 females) and 28 veterinarians in the same district were analysed serologically by RBPT, SAT and ELISA. Of the cattle sera analysed, 134 (32.92%) and 141 (34.64%) were determined as positive by RBPT and SAT, respectively. Thirty-two (13%), 35 (14.22%) and 44 (17.88%) of the farmers' sera were found positive for brucellosis by RBPT, SAT and ELISA, respectively. There was no significant difference between sexes for Brucella seropositivity. Of the 28 sera from veterinarians, 13 (46.42%) were positive by the three serological tests. The high prevalence of brucellosis both in cattle and humans suggests that brucellosis is common in this area. Preventive and control measures should be implemented and pursued more strictly to reduce and/or eradicate brucellosis from the area.

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Varicella Vaccine (VarilRix) in Children with Acute Lymphoblastic Leukemia.

Blood ◽

10.1182/blood.v104.11.4436.4436 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4436-4436

Author(s):

Teresa Jackowska Ass ◽

Robert Wasilewski ◽

Elzbieta Górska ◽

Maria Wasik ◽

Teresa Loch

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Lymphocytes ◽

Lymphoblastic Leukemia ◽

Varicella Vaccine ◽

White Blood Cells ◽

Healthy Children ◽

Varicella Zoster ◽

Significant Difference ◽

Before And After ◽

History Of

Abstract Background: To assess the effectiveness of vaccination against varicella in children with acute lymphoblastic leukemia (ALL). Methods: 105 children without a history of varicella, were qualified for immunization against varicella with VARILRIX (Oka-strain varicella vaccine). 48 children had ALL and 57 were healthy. 25 of the children with ALL were receiving maintenance therapy, 23 children were after chemotherapy. Results: White blood cells (WBC), lymphocytes, and sub-populations of T- and B-lymphocytes were compared in the healthy and leukemic children before and after vaccination. The ALL children had significantly lower counts of WBC and lymphocytes before vaccination. After vaccination there were no significant differences in the counts of WBC in the healthy and leukemic children. However the ALL children had significantly lower mean counts of lymphocytes. Before vaccination the leukemic children showed a significantly lowered percentage of T-lymphocytes with decreased CD4+ and increased CD8+, what resulted in a lowered CD4 to CD8 ratio. After vaccination, only increased numbers of T CD8+ lymphocytes and a lowered CD4 to CD8 ratio were present while there was no significant difference in CD4. In the healthy and leukemic children alike there was no statistically significant difference between B-lymphocytes (CD 19+) and NK cells. In 10 children (20%), out of the 48 ALL vaccines, varicelliform rash occurred ~1 month after immunization. No adverse effects we observed in healthy children. Seroconversion to varicella-zoster virus was higher in healthy children and ALL children who had skin rash after vaccination. Two ALL children and three healthy ones had varicella one-two years after the vaccination. Those children received only single vaccine doses (double vaccine doses received children above 12 years). Conclusion: Varicella vaccine was safe and immunogenic in leukemic children during maintenance and after chemotherapy.

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Serological Evaluation of Anti-Toxoplasma gondii Antibodies in Patients with Acute Leukemia and Lymphoma through Chemotherapy

Iranian Journal of Parasitology ◽

10.18502/ijpa.v15i2.3300 ◽

2020 ◽

Author(s):

Fatemeh TABATABAIE ◽

Taher ELMI ◽

Majid KHANMOHAMMADI ◽

Lame AKHLAGHI ◽

Mahmoud MAHAMI-OSKOUEI ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Acute Leukemia ◽

Lymphoblastic Leukemia ◽

Treatment Phase ◽

Protozoan Parasite ◽

Toxoplasma Infection ◽

Igg Avidity ◽

Significant Difference ◽

History Of ◽

Pre Treatment

Background: Toxoplasma gondii is a protozoan parasite that belongs to the family Coccidae. We aimed to evaluate IgG avidity and the changes of anti-Toxoplasma immunoglobulins M (IgM) and G (IgG) in patients with acute leukemia and lymphoma. Methods: Ninety eight patients with Acute myeloid leukemia (AML), Acute Lymphoblastic Leukemia (ALL) and lymphoma, selected from patients referring to Imam Reza Hospital of Tabriz (38°04′N 46°18′E), in terms of the presence of anti-Toxoplasma IgM, IgG, IgG avidity antibodies and the major risk factors were evaluated. Results: The results of pre-chemotherapy evaluation showed that of the examined patients, only two cases, one patient with ALL and another patient with lymphoma, had a positive IgM titer. Overall, 46 cases had positive IgG titers, including 20 patients with AML, 15 patients with ALL and 11 patients with lymphoma. Three (3.06%) patients were positive for anti-T. gondii IgM and one of them was with new infection of toxoplasmosis in lymphoma patients. The post-chemotherapy IgG titer evaluation showed 46 [46.9% (95% CI 37.4–56.7)] positive IgG cases that this result was similar to the result of pre-treatment phase. One [1% (95% CI 0.2–5.6)] positive IgG avidity case was detected using ELISA method, in a patient with lymphoma whose IgM was also positive. There was no significant difference between the type of leukemia and the history of contact with cat. Conclusion: Performing specialized tests to diagnose toxoplasma infection before starting treatment, in immunodeficiency patients who undergo chemotherapy, is necessary; therefore, these tests should be considered in therapeutic protocols.

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Physiological and Chemical Study to Evaluation the Epidemiology of Acute Lymphocytic Leukemia for Patients without a Family History of Cancer in Karbala City, Iraq

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.v9i2.13634 ◽

2018 ◽

Vol 9 (2) ◽

Author(s):

Humam Ali Hade ◽

Rasha Hasan Jasim ◽

Sattar Jasim Hatrosh

Keyword(s):

Family History ◽

Acute Lymphocytic Leukemia ◽

Chemical Study ◽

Study Groups ◽

Lymphocytic Leukemia ◽

Control Group ◽

Serum Samples ◽

Significant Difference ◽

History Of ◽

Males And Females

During the period from the beginning of February 2016 to the end of October 2017 in the Center of Oncology of Hematology of El-Hussein Medical city in Karbala, 30 samples were collected for patients with acute lymphocytic leukemia ranging between 1-13 years old (6,80 ± 3, 79) who didn’t have a family history of any cancer infection before receiving chemotherapy. The study was divided into two sections based on sex. The study included 19 males aged (1 - 12 years) and 11 females aged (1- 13 years old). The results showed significant differences in the levels of trace elements (Fe), (Cu), (Zn) and (Ni) in the serum. There was significant difference (p = 0.00) between the healthy and the patients who didn’t gain medicine. Also, significant differences were in levels of fe) and Cu (cu) in serum samples in the samples of males and females with their peers in the control group. There were also significant differences when comparing the sexes in each of the two study groups. The results also showed significant differences in zn Blood samples for male and female patients with acute lymphocytic leukemia and healthy individuals, while significant differences of Ni (ni) between males and females of the infected group and healthy males.

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Thrombotic Events in Adults with Acute Lymphoblastic Leukemia.

Blood ◽

10.1182/blood.v104.11.2734.2734 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2734-2734

Author(s):

Christine M. Cserti ◽

Joseph Brandwein ◽

Jeffrey H. Lipton ◽

Anne G. McLeod ◽

Hans Messner ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Median Time ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Treatment Protocol ◽

High Dose ◽

Cell Subtype ◽

Significant Difference ◽

History Of

Abstract A strong link between asparaginase-containing (ase +) chemotherapy regimens and venous thrombotic events (VTE) has been established for pediatric acute lymphoblastic leukemia (ALL), but this association has not been studied in adult ALL. We recently adopted as our first-line therapy for adult ALL a treatment protocol (DFCI 00–01) that employs weekly high-dose ase throughout a 27 week intensification phase. We reviewed the records of 92 adult patients consecutively accrued at Princess Margaret Hospital (from Jan 2000 to Dec 2003) for venous thrombotic events (VTE). Median age at diagnosis of ALL was 41±17 y, or 19±3 y for those who presented after a history of pediatric ALL (n=6), and 42±16 y for adults who presented with de novo ALL (n=86). Thirty-five (37%) were female, 59 (63%) male. Twenty-four (26%) were Philadelphia-chromosome positive; 71% of these received regimens containing imatinib. At least 1 symptomatic, radiologically confirmed VTE was seen in 19 patients (21%), with 3 (3%) diagnosed prior to any antileukemic therapy. Overall survival (OS) versus thrombosis-free survival (TFS) is illustrated in the Kaplan-Meier curve below. Median time to VTE was 94±92 d [95% CI]. Average age of patients with VTE was 44 ±15y; no events were observed in patients with a prior pediatric history of ALL. The sites of VTE were: 10/22 (46%) in the lower extremities, 5/22 (23%) propagating from central venous access catheters (CVAC), 4/22 (18%) as pulmonary emboli (2 in isolation), and 3/22 (14%) CNS (2 cerebral venous sinus and 1 retinal venous thrombus). The first antileukemic regimen administered was DFCI 00–01 ± imatinib in 79/92 (86%), HyperCVAD ± imatinib in 7 (8%), an unclassified ase+ regimen in 1 (1%), or an unclassified asparaginase-excluding (ase−) regimen in 5 (5%). A significant difference in the rate of ase-dependent VTE was observed when all regimens (1° or subsequent) were counted, with 18 VTE during 103 ase+ regimens (17.5%), versus only 1 VTE in 32 ase− regimens (3.1%), [p=0.04]. Median time to VTE in DFCI 00-01was 109±98d, most often occurring during the intensification phase. The odds ratio for VTE with any T-cell subtype of ALL compared to any B-cell subtype was 4.6 [p=0.0043]. Conclusions : A high, significant VTE rate (~18%) was observed in adults with ALL undergoing ase+ antileukemic therapy, nearly 6X the rate observed either prior to treatment or during ase− regimens (~3%). Ase is thus strongly associated with VTE, warranting improved surveillance and antithrombotic prophylaxis. Risk factors (underlying thrombophilias, leukemic subtypes) similarly deserve further study. Figure Figure

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Serum oxidative stress influences neurological recovery after surgery to treat acutely worsening symptoms of compression myelopathy: a cross-sectional human study

BMC Musculoskeletal Disorders ◽

10.1186/s12891-019-2966-5 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Hiroshi Takahashi ◽

Yasuchika Aoki ◽

Junya Saito ◽

Arata Nakajima ◽

Masato Sonobe ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen ◽

Serum Levels ◽

Neurological Recovery ◽

Reactive Oxygen Metabolites ◽

Serum Samples ◽

Cross Sectional ◽

Significant Difference ◽

History Of ◽

Compression Myelopathy

Abstract Background Recent reports indicate that oxidative stress induced by reactive oxygen species is associated with the pathobiology of neurodegenerative disorders that involve neuronal cell apoptosis. Here we conducted a cross-sectional study to evaluate serum levels of oxidative stress in cervical compression myelopathy. Methods Thirty-six serum samples were collected preoperatively from patients treated for acutely worsening compression myelopathy (AM) and chronic compression myelopathy (CM). Serum levels of oxidative stress markers were evaluated by measuring derivatives of reactive oxygen metabolites (ROM), which reflect concentrations of hydroperoxides. ROM in healthy individuals range from 250 to 300 (U. CARR), whereas ROM >340–400 and > 400 define moderate and severe levels of oxidative stress, respectively. Difference of ROM by the cause of disorders whether cervical spondylotic myelopathy (CSM) or cervical ossification of longitudinal ligament (OPLL), correlations between ROM and patient age, body mass index (BMI), history of smoking, existence of diabetes were examined. Neurological evaluations according to Japanese Orthopaedic Association (JOA) scores were performed and correlated with ROM. Results ROM increased to 349.5 ± 54.8, representing a moderate oxidative stress, in CM samples. ROM increased to 409.2 ± 77.9 in AM samples, reflecting severe oxidative stress which were significantly higher than for CM samples (p < 0.05). There was no significant difference by the cause of disorders (CSM or OPLL). ROM were significantly increased in AM serum samples from female patients versus AM male and CM patients (p < 0.05). There were no correlations between ROM and age, BMI, history of smoking, and existence of diabetes. A negative correlation between ROM and recovery rate of JOA score (R2 = 0.454, p = 0.047) was observed in the AM group. Conclusions Although moderate oxidative stress was present in patients with CM, levels of oxidative stress increased in severity in patients with AM. These results suggest that postsurgical neurological recovery is influenced by severe oxidative stress in AM.

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Prevalence and Risk Factors of ESBL-producing Enterobacteriaceae in The Community

Journal of Biomedicine and Translational Research ◽

10.14710/jbtr.v7i1.10051 ◽

2021 ◽

Vol 7 (1) ◽

pp. 1-6

Author(s):

Nia Krisniawati ◽

Anriani Puspita Karunia Ning Widhi

Keyword(s):

Multivariate Logistic Regression Analysis ◽

World Health ◽

Bivariate Analysis ◽

Multivariate Logistic Regression ◽

Asymptomatic Carriers ◽

E Coli ◽

Significant Difference ◽

History Of ◽

High Carrier ◽

Health Organization

Background: World Health Organization (WHO) data collection of Escherichia coli resistant to cephalosporin generation III already confirmed in 86 countries. Incredibly high carrier prevalence rates were also widely developed in Thailand, Egypt, and China. The Faculty of Medicine's research team at Jenderal Soedirman University, Purwokerto, discovered at the beginning of 2018 that Extended Spectrum β-Lactamase (ESBL) E. coli carriers throughout the 2015 class students were 26.8 percent.Objective: This research investigated the Prevalence and associated factors of ESBL-producing Enterobacteriaceae (EPE) asymptomatic carriers in the community.Methods: The participant fill a questionnaire, and samples were taken from rectal swabs using Amies transport medium (Labware Charuzu), and then models were analyze using HiCrome ™ ESBL Agar Base (Himedia, India). Analysis of its Prevalence and Resistance Predictors uses IBM SPSS Statistics Version 22.0 for Windows (Armonk, NY: IBM Corp).Results: The Prevalence of EPE asymptomatic carriers in the community in Purwokerto was 66.7%. In the bivariate analysis, subjects who took antacids in the last eight weeks, history of hospitalization in the previous 12 months, the habit of consuming milk, yogurt, cheese, meat, seafood, and raw vegetables did not show any significant difference. Frequent chicken and freshwater fish consumption tended to be a risk factor for ESBL-producing Enterobacteriaceae with PR 1.462, 95% CI (1.115-1.918); PR 1.666, 95% CI (0.936-2.966); however, in the multivariate logistic regression analysis, this was not significant.Conclusion: The Prevalence of EPE asymptomatic carriers in the community in Purwokerto is 66.7%. All variables did not become any significant of ESBL-producing Enterobacteriaceae. However, ESBL remains an emerging antimicrobial resistance.

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L-Asparaginase (L-ASP) Related Toxicities with Asparaginase Erwinia Chrysanthemi in a Large Compassionate Use Protocol.

Blood ◽

10.1182/blood.v120.21.2568.2568 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2568-2568

Author(s):

Paul V. Plourde ◽

Sima Jeha ◽

Nobuko Hijiya ◽

Frank G Keller ◽

Susan R. Rheingold ◽

...

Keyword(s):

Allergic Reaction ◽

Treatment Plan ◽

Lymphoblastic Leukemia ◽

Safety Information ◽

Erwinia Chrysanthemi ◽

Hypersensitivity Reactions ◽

Compassionate Use ◽

E Coli ◽

History Of ◽

Multi Agent

Abstract Abstract 2568 Background: L-asparaginase (L-ASP) is an important component of multi-agent chemotherapy for treatment of Acute Lymphoblastic Leukemia (ALL) in children and young adults. The pegylated E. coli derived form, Oncaspar® (PEG-ASP), is most commonly used because of its longer half-life and lower immunogenicity compared to the native enzyme; however, clinical hypersensitivity reactions still occurs in 10–30% of patients (pts) requiring its discontinuation. Asparaginase Erwinia Chrysanthemi (Erwinaze™) is an L-ASP derived from a different bacterium and is immunologically distinct from the E. coli L-ASP. We conducted a compassionate use trial of Erwinaze in pts with ALL and hypersensitivity to native E. coli or PEG-ASP to collect safety information. Patients and Methods: Pts of any age with ALL or lymphoblastic lymphoma (LBL) who developed a Grade ≥2 clinical hypersensitivity reaction to PEG-ASP or native E. coli ASP (Elspar®) were eligible. Pts with a history of pancreatitis, previous allergic reaction to Erwinaze, or pregnant, were excluded. The study was IRB approved at each institution and pts/family provided informed consent/assent. Safety information on Erwinaze-related adverse events (AEs) were captured on Case Report Forms (CRFs) submitted to the Sponsor when the pt completed his/her entire Erwinaze treatment plan. AEs may have also been reported directly by the investigational sites. Results: Between February 2006 and November 2011, 1,368 pts were treated with Erwinaze. CRFs were received in 893 pts and 47 additional AEs were received from patients for which a CRF was not obtained. The average age was 9.6 years (range 1–66). The majority of patients (63.5%) were male. Of the pts for which CRFs were received (893); 77.6% were able to conclude their Erwinaze treatment. Discontinuation was due to allergic reaction in 8.8%; other AEs 4.7%; at the physician or patient discretion 7.5%; and missing information in 1.3%. Anaphylaxis was reported in 8 pts (0.9%) and Grade ≥2 clinical hypersensitivity reactions in 130 (13.8%). The incidence of pancreatitis was 3.9%, hemorrhagic or thrombosis abnormalities 2.4%, hyperglycemia 3.6% and elevation in liver enzymes 3.5%. There were 18 deaths on study; 11 disease progression, 3 intracranial hemorrhage, 4 other individual reports. Conclusion: This is the largest study of pts treated with Erwinaze to determine the toxicity profile. Erwinaze was well tolerated with no unexpected toxicities identified beyond those associated with L-Asp treatment. This compassionate use trial permitted the continuation and completion of asparaginase treatment in 77.6% of pts with hypersensitivity reactions to E. coli formulations. Final results will be available for presentation. Disclosures: Plourde: Jazz Pharmaceuticals: Employment, Equity Ownership. Mercedes:Jazz Pharmaceuticals: Employment. Corn:EUSA Pharma: Employment.

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Anti–Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials

Blood ◽

10.1182/blood-2011-07-367904 ◽

2011 ◽

Vol 118 (22) ◽

pp. 5774-5782 ◽

Cited By ~ 39

Author(s):

Andrea Willer ◽

Joachim Gerß ◽

Thorsten König ◽

Dieter Franke ◽

Hans-Jürgen Kühnel ◽

...

Keyword(s):

Escherichia Coli ◽

Retrospective Analysis ◽

Rank Order ◽

Lymphoblastic Leukemia ◽

Line Treatment ◽

Second Line ◽

Serum Samples ◽

E Coli ◽

Relapsed Disease ◽

Antibody Levels

Abstract Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti–E coli ASE Ab levels (P < .0001; Spearman rank order correlation). An effect on ASE activity during second-line treatment with pegylated E coli ASE was, however, only observed when anti–E coli ASE Ab levels were high (> 200 AU/mL). In the presence of moderate or intermediate Ab levels (6.25-200 AU/mL) the switch from native to pegylated E coli ASE resulted in a significant increase of ASE activity above the threshold of 100 U/L (P < .05). Erwinia chrysanthemi ASE activity was not correlated with anti–E coli ASE Ab levels. Erwinia ASE was found to be the best ASE alternative if Ab levels against E coli ASE exceed 200 AU/mL. This retrospective analysis is the first to describe the relationship between the level of anti–E coli ASE Abs and serum activity of pegylated E coli ASE used second-line after native E coli ASE. These studies are registered at http://clinicaltrials.org as NTC00430118 and NCT00114348.

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