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

Blood ◽  
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.

Safety of asparaginase Erwinia chrysanthemi in a compassionate-use trial: Subanalysis of the adolescent/young adult (AYA) and adult patient (Pt) population.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7097-7097
Author(s):  
Paul V. Plourde ◽  
Sima Jeha ◽  
Nobuko Hijiya ◽  
Frank G. Keller ◽  
Susan R. Rheingold ◽  
...  
Keyword(s):  
Hypersensitivity Reaction ◽  
Allergic Reaction ◽  
Lymphoblastic Leukemia ◽  
Safety Information ◽  
Erwinia Chrysanthemi ◽  
Compassionate Use ◽  
Entire Study ◽  
Nccn Guidelines ◽  
E Coli ◽  
Study Population

7097 Background: The AYA population is usually defined as pts aged 16 to 39 years. NCCN guidelines recommend that AYA patients with acute lymphoblastic leukemia (ALL) be treated with ‘pediatric-inspired’ protocols that includeL-asparaginase (L-ASP) as an integral component of their multiagent chemotherapy regimen. Hypersensitivity reaction is the most common toxicity associated with L-ASP treatment, occurring in 10%–30% of pts treated with E coli–derived L-ASP, necessitating its discontinuation. In those pts, it is recommended that L-ASP derived from Erwinia chrysanthemi (Erw) be initiated since it is immunologically distinct from E coli–derived L-ASP. Methods: A large compassionate-use trial in pts with ALL or lymphoblastic lymphoma who developed a hypersensitivity reaction (ie, grade ≥2) to an E coli–derived L-ASP was conducted to evaluate the safety of Erw. Pts were excluded if they had a history of pancreatitis, previous allergic reaction to Erw, or were pregnant. Adverse events (AEs) and/or case report forms were completed for 940 pts. The Erw safety information for the full study population was previously reported. Here, we report a safety analysis of pts aged ≥16 years with the majority being AYA (94%), a population in which little Erw safety information has been presented. Results: In this compassionate-use trial, 156 pts were aged ≥16 years. These pts were primarily male (67.9%), had nonrelapsed disease (70.5%), B-lineage ALL (71.2%), and received intramuscular Erw (85.9%). 71.8% completed their planned Erw course. Reasons for discontinuation included allergic reaction (3.2%), other AEs (9.6%), other reasons (6.4%), and unknown reasons (9%). Hypersensitivity occurred in 20 (12.8%); hyperglycemia, 9 (5.8%); pancreatitis, 6 (3.8%); thrombosis, 5 (3.2%); bleeding, 1 (1%). Grade 3/4 AEs with a >5% incidence included hyperglycemia (5.8%). There were 10 deaths: 4 disease progression, 3 infection, 1 coma, 1 renal impairment, 1 unknown. Conclusions: The safety profile of Erw in pts ≥16 years was consistent with the profile in the entire study population. This compassionate-use trial permitted the completion of L-ASP in 71.8% of AYA and adult pts. Clinical trial information: NCT00693602.

Preliminary Results Of a Pharmacokinetic Study Of Intravenous Asparaginase Erwinia Chrysanthemi Following Allergy To E Coli-Derived Asparaginase In Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia Or Lymphoblastic Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3904-3904 ◽  
Author(s):  
Lynda M. Vrooman ◽  
Ivan I. Kirov ◽  
Zoann E. Dreyer ◽  
Michael Kelly ◽  
Nobuko Hijiya ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Children And Adolescents ◽  
Treatment Plan ◽  
Lymphoblastic Leukemia ◽  
Advisory Board ◽  
Lymphoblastic Lymphoma ◽  
Erwinia Chrysanthemi ◽  
Primary Study ◽  
E Coli ◽  
Original Treatment

Abstract Background Asparaginase is an important component of therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). However, up to 30% of patients (pts) develop an allergy to Escherichia coli (E coli)–derived asparaginase. In those pts, Erwinia asparaginase (Erwinia), an antigenically distinct preparation derived from Erwinia chrysanthemi, can be used. Although Erwinia is typically administered intramuscularly (IM), intravenous (IV) asparaginase would offer a more convenient, less painful administration route. In an open-label, single-arm, multicenter, pharmacokinetic (PK) study, we evaluated IV administration of Erwinia in children and adolescents with ALL who developed hypersensitivity to E coli–derived asparaginase. Methods Pts (aged ≥1 to ≤30 years) with ALL or LBL who developed hypersensitivity (grade ≥2) to E coli–derived asparaginase were eligible for enrollment. Pts received Erwinia IV, 25,000 IU/m2/dose, on a Monday/Wednesday/Friday (M/W/F) schedule for 2 consecutive weeks (6 doses=1 cycle) for each dose of pegaspargase remaining in the original treatment plan. All other chemotherapy was continued per the original treatment plan. Blood samples were collected during the 1st treatment cycle, including predose, 5 min, 48 hrs and 72 hrs postdose. The primary study objective was to determine the proportion of pts who achieved nadir serum asparaginase activity (NSAA) ≥0.1 IU/mL, which has been associated with complete asparagine depletion, at 48 hrs after dose 5 in cycle 1. Secondary objectives included determining the proportion of pts who achieved NSAA ≥0.1 IU/mL at 72 hrs after dose 6 in cycle 1 and the incidence of asparaginase-related toxicities. Only pts who completed 1 cycle of Erwinia were considered evaluable for NSAA assessment. Results Between November 2012 and June 2013, 30 pts were enrolled from 10 centers; 26 pts completed cycle 1. Twenty-three pts were evaluable for the primary NSAA endpoint (3 pts were not evaluable; 2 for PK data collected outside the protocol-specified window and 1 for nonadherence to the dosing schedule). Median age was 6.5 years (1-17 years), 63% were male, and 83% Caucasian. Predose NSAA levels were below the limit of quantification (defined as 0.0129 IU/mL) for nearly all (91%) pts. Of the 23 evaluable pts who completed cycle 1, 19 (83%) achieved NSAA levels ≥0.1 IU/mL at 48 hrs postdose 5, with mean ±SD NSAA 0.32 ±0.23 (Table 1). At 72 hrs postdose 6, 9 pts (45%) achieved NSAA levels ≥0.1 IU/mL (mean ±SD 0.088 ±0.076). Four pts discontinued Erwinia treatment before completing cycle 1; 3 for hypersensitivity and 1 for pancreatitis. The toxicity analysis included all 30 enrolled pts. The most common asparaginase-related toxicities reported during cycle 1 were: hypersensitivity (23% of pts), vomiting (20%), nausea (20%), and hyperglycemia (13%). Pancreatitis occurred in 3% and thrombosis in 3% of pts. One pt experienced a transient ischemic attack. The most common grade 3 or 4 adverse event was febrile neutropenia (7%). There were no deaths. Conclusions The majority (83%) of children and adolescents with ALL or LBL receiving Erwinia IV at 25,000 IU/m2/dose on a M/W/F schedule, achieved NSAA ≥0.1 IU/mL at 48 hrs postdose 5 (considered the therapeutic goal); however the majority did not achieve this goal at 72 hrs post Erwinia dose 6. With IV administration, asparaginase-related toxicities appeared to be consistent with previous reports in children treated with IM Erwinia. Based on these results, we are now evaluating IV Erwinia at 25,000 IU/m2/dose administered every 48 hrs rather than on a M/W/F schedule. This study was funded by Jazz Pharmaceuticals plc. Disclosures: Off Label Use: ERWINAZE (asparaginase Erwinia chrysanthemi) is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL)who have developed hypersensitivity to E. coli-derived asparaginase. The recommended dose is 25,000 International Units/m2 administered intramuscularly three times a week (Monday/Wednesday/Friday) for six doses for each planned dose of pegaspargase. Hijiya:Jazz Pharmaceuticals: Consultancy. Brown:Jazz Pharmaceuticals: advisory board Other. Drachtman:Jazz Pharmaceuticals: Honoraria. Messinger:Jazz Pharmaceuticals: Advisory Board Other. Plourde:Jazz Pharmaqceuticals: Employee of Jazz Pharmaceuticals, Inc, who in the course of this emplyment has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc Other, Employment. Silverman:Enzon Pharmaceuticals: Consultancy; Sigma Tau Pharmaceuticals: Advisory Board, Advisory Board Other; EUSA Pharma: Advisory Board Other.

A phase II/III study of JZP-458 in patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who are hypersensitive to E. coli-derived asparaginases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS7568-TPS7568
Author(s):  
Luke Maese ◽  
Rachel E. Rau ◽  
Elizabeth A. Raetz ◽  
Tong Lin ◽  
Pil Kim ◽  
...  
Keyword(s):  
Treatment Plan ◽  
Lymphoblastic Leukemia ◽  
Phase 1 ◽  
Surrogate Marker ◽  
Dose Schedule ◽  
Cross Reactivity ◽  
Hypersensitivity Reactions ◽  
Open Label ◽  
E Coli ◽  
Expression Platform

TPS7568 Background: L-asparaginase is an important component of ALL therapy and the inability to receive asparaginase secondary to hypersensitivity has been associated with poor patient (pt) outcomes. Alternative options for pts after hypersensitivity reactions are needed. JZP-458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme with no immunologic cross-reactivity to E. coli–derived asparaginases. In a phase 1 study, JZP-458 was well tolerated and maintained adequate (≥0.1 IU/mL) serum asparaginase activity (SAA), a surrogate marker for asparagine depletion, for up to 72 hrs in healthy adults. Methods: This is a pivotal, open-label, multicenter, dose confirmation, and pharmacokinetic (PK) study (NCT04145531) of JZP-458 in pts with ALL/LBL who develop hypersensitivity reactions to a long-acting E. coli–derived asparaginase and have ≥1 course of asparaginase remaining in their treatment plan (Table); 6 doses of JZP-458 will be substituted for each remaining course. Treatment duration will depend on the number of asparaginase courses remaining in the treatment plan. The study has 2 sequential parts: Part A will determine the dose of intramuscular (IM) JZP-458 and confirm safety/efficacy; Part B will explore the dose/schedule of intravenous (IV) JZP-458. Blood samples will be collected to determine SAA levels and pts will be monitored for adverse events. Immunogenicity of JZP-458 will be assessed. Primary objectives are to determine (1) the efficacy of IM JZP-458 measured by the last 72-hr nadir SAA (NSAA) level (≥0.1 IU/mL) during the first treatment course, and (2) the safety/tolerability of IM JZP-458. Secondary objectives are to determine the efficacy (measured by the last 48-hr NSAA level [≥0.1 IU/mL] and the last 48- and 72-hr NSAA levels [≥0.4 IU/mL]), PK, and immunogenicity of IM JZP-458. Exploratory objectives include efficacy, safety, PK, and immunogenicity of IV JZP-458. The trial is active and enrolling. Clinical trial information: NCT04145531 . [Table: see text]

Occurrence of Pleural/Pericardial Effusions in Ph+ CML Patients Failing Prior Tyrosine Kinase Inhibitors (TKI) Before Starting Nilotinib – Retrospective Analysis upon Entry into the Nilotinib Compassionate Use Program

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4271-4271 ◽  
Author(s):  
Philipp D. le Coutre ◽  
Michael O’Dwyer ◽  
Tomasz Szczudlo ◽  
Richard C. Woodman ◽  
Francis J. Giles
Keyword(s):  
Pleural Effusion ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Safety Information ◽  
Chronic Phase ◽  
Pleural Effusions ◽  
Compassionate Use ◽  
Pericardial Effusions ◽  
History Of

Abstract Background: Imatinib, nilotinib, and dasatinib are BCR-ABL tyrosine kinase inhibitors (TKIs), with different selectivity profiles, approved for the treatment of patients (pts) with Philadelphia positive chronic myeloid leukemia (Ph+ CML). Given the differences in their kinase selectivity profiles, the safety profiles of these agents also differ, particularly with regard to episodes of fluid retention. The incidence of pleural/pericardial effusions in resistant or intolerant CML pts who failed imatinib, or both imatinib and dasatinib, therapy was evaluated. Methods: The occurrence of pleural/pericardial effusions in resistant or intolerant CML pts following therapy with imatinib, or imatinib and dasatinib sequentially, was evaluated in 915 pts with Ph+ CML in chronic phase (CML-CP, 60%), accelerated phase (CML-AP, 23%), and blast crisis (CML-BC 17%) who entered the nilotinib compassionate use program between June 2006 and April 2008. At the time of medical review for compassionate use approval, safety information including the presence of or the history of pleural/pericardial effusions was collected along with dosing information for imatinib and dasatinib. Nearly all pts analyzed (94%) had not received nilotinib therapy prior to inclusion in the compassionate use program. Resistance and intolerance as well as CML phase were defined using similar criteria as previously reported in the nilotinib pivotal phase I/II study. Results: The median age was 52 years (range: 11 – 87 years); 22 pts (2%) were 18 years old or younger. Most pts (734; 80%) had received prior imatinib only (64% discontinued due to resistance, 20% with resistance and intolerance and 16% due to intolerance) and 170 pts received both imatinib and dasatinib (29% resistant; 17% with resistance and intolerance, 54% intolerant), with most dasatinib failures being due to toxicity. Information on past treatment is currently unavailable for 11 pts. Of pts who were pretreated with imatinib alone, less than 2% of pts (n = 11) had pleural and/or pericardial effusions reported. Among those pts pretreated with both imatinib and dasatinib, 51 pts (30%) had pleural and/or pericardial effusions, with 50 (98%) having pleural effusions, 10 of which were bilateral. Fifty-five percent of pts with pleural and/or pericardial effusions were in chronic phase. Of the pts with dasatinib-associated pleural/pericardial effusions; 11% were noted on daily doses > 140 mg, 29% on doses of 140 mg, 20% on doses of 100 mg, and 10% on doses of < 100 mg. There were 14 pts who developed pleural and/or pericardial effusions in which the dasatinib dose was not available. Of the 33 pts with pleural and/or pericardial effusions on daily 140 mg dasatinib, 16 pts (48%) discontinued dasatinib due to pleural effusion and 6 pts exhibited persistent pleural effusions despite dasatinib dose reductions. One pediatric patient (age 11 years) had a pleural effusion with once daily 80 mg dasatinib. Pleural/pericardial effusions occurred in all age groups: >50 years old – 6 pts, 51–60 years old – 10 pts; 61–70 years old – 13 pts; 71–80 years old – 16 pts and >81 years old – 4 pts (2 of unknown age). No pts who developed dasatinib-associated pleural/pericardial effusions had a history of pleural/pericardial effusions during imatinib therapy. Conclusions: This large dataset supports earlier reports that pleural/pericardial effusions are frequently reported among CML pts treated with dasatinib compared with imatinib. Furthermore, the occurrence of dasatinib-associated pleural/pericardial effusions may occur at any dose, even below the standard 140 mg/day dose and in some cases with doses less than 100 mg/day.

Anti-Leukemic Activity of a Novel Pegylated Recombinant Erwinia Chrysanthemi-Derived L-Asparaginase On Lymphoid Cell Lines and Leukemia-Bearing Mouse Models.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2571-2571 ◽  
Author(s):  
Wei-Wen Chien ◽  
Céline Lebeux ◽  
Nicolas Rachinel ◽  
Soraya Allas ◽  
Pierre Sahakian ◽  
...  
Keyword(s):  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Lymphoma Cell ◽  
Erwinia Chrysanthemi ◽  
Leukemic Cells ◽  
Hypersensitivity Reactions ◽  
Sensitive Cell ◽  
Development Fund

Abstract Abstract 2571 Background: Bacterial-derived L-asparaginase (ASNase) is an indispensable component of the therapy of acute lymphoblastic leukemia (ALL). Despite the high rate of successful treatment, hypersensitivity reactions occur in 20–40 % of patients receiving this non-human protein, which limits the use of ASNase. Native Erwinia chrysanthemi-derived ASNase (n-crisantaspase) has been used for treating patients exhibiting allergic symptoms to native and PEGylated Escherichia coli-derived ASNases (EC-ASNase). However, hypersensitivity reactions are still observed in at least 17 % of patients receiving n-crisantaspase. A PEGylated recombinant Erwinia chrysanthemi-derived ASNase (PEG-r-crisantaspase) with improved pharmacokinetic and pharmacodynamics properties and reduced immunogenicity has been developed recently (Allas et al., abstracts #2003, #2034, ASH 2009). We present here the in vitro and in vivo evaluation of PEG-r-crisantaspase on leukemia and lymphoma cell lines and on a leukemia-bearing mouse model, respectively. Material and methods: Different cell lines (ALL, B, T and NK/T lymphoma) and bone marrow aspiration samples obtained from patients with B-ALL or T-ALL were exposed in vitro to increasing doses (0.00005 to 5 U/ml) of PEG-r-crisantaspase, n-crisantaspase, or native EC-ASNase for 3 days. The cytotoxicity of each molecule was evaluated using 3- (4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. For the in vivo study, 5 millions of ASNase-sensitive cells, RS(4,11) were xenografted by intravenous injection (iv) into immunodeficient NOD/SCID mice. When 5% of leukemic blasts were observed in the blood of leukemia-bearing mice, 2, 5, 10 or 20 U/kg of PEG-r-crisantaspase or vehicle was injected intravenously in those mice. Two additional injections were performed with an interval of 7 days. Mice having significant weight loss (>20%) and/or extensive expansion of leukemic cells in blood (> 25%) and/or impaired general condition were sacrificed. Results: In vitro, PEG-r-crisantaspase and n-crisantaspase exhibited similar half maximal effective concentration (EC50) values for inhibiting the proliferation of leukemia and lymphoma cells. PEG-r-crisantaspase had a greater cytotoxicity effect on two high-sensitive cell lines than n-crisantaspase did, as shown by 4.5 and 8.1-fold-weaker EC50 values of PEG-r-crisantaspase relative to n-crisantaspase. PEG-r-crisantaspase, r-crisantaspase and n-crisantaspase were more efficient than EC-ASNase on less sensitive cell lines, which might be related to the 10-fold-greater glutaminase activity of crisantaspases than EC-ASNase. In vivo, after the first administration of PEG-r-crisantaspase in animals with ≥ 5% of leukemic cells, the leukemic cells were reduced to almost 0 % in mice within 4 days with all doses of PEG-r-crisantaspase tested, whereas the leukemic cells kept multiplying in the mice receiving vehicle. The 3 repeated injections of PEG-r-crisantaspase with an interval of 7 days delayed leukemia development for 17 days. All control mice receiving the vehicle had to be sacrificed at day 44 after leukemia inoculation, whereas of 28 mice receiving PEG-r-crisantaspase, 5 reached this endpoint at day 51 and the others at day 56. PEG-r-crisantaspase significantly improved the survival of leukemia-bearing mice for 7 to 12 days, regardless of the dose tested. Conclusions: These data provide evidence that PEG-r-crisantaspase has similar in vitro cytotoxic effect to n-crisantaspase on leukemia and lymphoma cell lines and significantly reduces the expansion of leukemic cells in leukemia-bearing mice, prolonging the survival of the animals. These results, together with preclinical PK/PD and immunogenicity data, support the clinical development of PEG-r-crisantaspase. A phase I dose escalation study in adult patients with relapsed or refractory hematological malignancies has been recently initiated. Research support from Alizé Pharma, the European Regional Development Fund (ERDF) and Grand Lyon. Disclosures: Allas: Alizé pharma: Employment. Sahakian:Alizé pharma: Employment. Julien:Alizé pharma: Employment. Abribat:Alizé pharma: Employment.

scholarly journals ALLERGIC REACTION TO ESCHERICHIA COLI-ASPARAGINASE IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A STUDY IN A TERTIARY HOSPITAL IN INDONESIA

2020 ◽  
pp. 142-146
Author(s):  
NUR MELANI SARI ◽  
NABILLA PUTRI OSSEVA ◽  
NUR SURYAWAN
Keyword(s):  
Escherichia Coli ◽  
Acute Lymphoblastic Leukemia ◽  
Allergic Reaction ◽  
General Hospital ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Examination ◽  
Tertiary Hospital ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
E Coli

Objective: The objective of the study was to determine and describe the characteristics of allergic reactions to Escherichia coli-Asparaginase (E. coli-ASP). Methods: This cross-sectional study was performed at Hasan Sadikin Bandung General Hospital on acute lymphoblastic leukemia patients diagnosed from January 1, 2018, to August 31, 2019, confirmed by bone marrow examination. Data were extracted from Bandung Online Pediatric Cancer Registry, medical records, protocol therapy documents, and interview with patient’s guardian. Results: Out of 68 patients, 26 patients (37.6%) were allergic to E. coli-ASP. Twenty-two patients with recorded manifestation’s data evoked 35 symptoms and graded according to common terminology criteria for adverse event v3.0., fever, and urticaria are the most frequent manifestation. While Grade 2 and Grade 3 are the most often developed allergic reaction, patients with age range from 1 to 14 years, male and high risk is mainly allergic. Conclusion: Allergic rate to E. coli-ASP at Hasan Sadikin General Hospital is 37.6%. The most frequent manifestation is fever and urticaria (20%, respectively), Grades 2 and 3 (32%, respectively), and emerged mostly after administration of fourth dose E. coli-ASP (26.9%). Despite the characteristic differences between allergic and non-allergic group, it is not statistically significant.

Comparative pharmacokinetic studies of three asparaginase preparations.

1993 ◽  
Vol 11 (9) ◽  
pp. 1780-1786 ◽  
Author(s):  
B L Asselin ◽  
J C Whitin ◽  
D J Coppola ◽  
I P Rupp ◽  
S E Sallan ◽  
...  
Keyword(s):  
Initial Dose ◽  
Half Life ◽  
Lymphoblastic Leukemia ◽  
Pharmacokinetic Studies ◽  
Serum Samples ◽  
E Coli ◽  
Significant Difference ◽  
History Of ◽  
Repeated Use ◽  
Repeated Doses

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.

Hypersensitivity Reactions to Etoposide

1996 ◽  
Vol 30 (4) ◽  
pp. 367-371 ◽  
Author(s):  
Richard MW Hoetelmans ◽  
Jan H Schornagel ◽  
Wim W ten Bokkel Huinink ◽  
Jos H Beijnen
Keyword(s):  
Drug Therapy ◽  
Hypersensitivity Reaction ◽  
Allergic Reaction ◽  
Polysorbate 80 ◽  
Hypersensitivity Reactions ◽  
Case Summary ◽  
Testicular Carcinoma ◽  
History Of

OBJECTIVE: To report a hypersensitivity reaction to etoposide occurring in a patient after 2 months of drug therapy. CASE SUMMARY: a 20-year-old man with a diagnosis of testicular carcinoma was treated with bleomycin, etoposide, and cisplatin (BEP regimen). After dose 20 of etoposide, an exanthema was noted, which was attributed to etoposide. The patient had received 19 doses of etoposide during the previous 2 months without any sign of an allergic reaction. Rechallenging the patient with etoposide from another batch resulted in recurrence of the exanthema. DISCUSSION: Both etoposide and its excipient (polysorbate 80) are suspected of causing hypersensitivity reactions. Although the exact mechanism of the hypersensitivity reaction is not known, it is believed to be of nonimmunogenic origin. CONCLUSIONS: With a lower rate of infusion of etoposide and/or by premedication with antihistamines and/or corticosteroids, hypersensitivity reactions to etoposide might be prevented in patients with a history of hypersensitivity to this drug.

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