Therapy with Erwinia l-asparaginase in children with acute leukemia after anaphylaxis to E. coli l-asparaginase

King, Oscar Y.; Wilbur, Jordan R.; Mumford, David M.; Sutow, Wataru W.

doi:10.1002/1097-0142(197403)33:3<611::aid-cncr2820330303>3.0.co;2-u

Cited by 29 publications

(12 citation statements)

References 8 publications

(2 reference statements)

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“…4,5,9,15,20 All reacting patients, except for one, reacted to E. coli asparaginase after 10 doses, but those who subsequently reacted to Erwinia asparaginase reacted shortly thereafter, within seven doses. Evans et al 4 observed that the risk of anaphylactoid reactions to Erwinia asparaginase was significantly greater in patients who had previously reacted to E. coli asparaginase, and that the risk of a reaction was related to the total number of asparaginase doses given.…”

Section: Figurementioning

confidence: 99%

Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia

et al. 1998

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Asparaginase is an effective antileukemic agent and is included in most front-line protocols for pediatric acute lymphoblastic leukemia (ALL) worldwide; however, allergic reactions to asparaginase may be dose-limiting. We evaluated plasma anti-asparaginase antibody concentrations in a cohort of children with newly diagnosed ALL, who did and who did not exhibit clinical hypersensitivity, after Escherichia coli (E. coli) asparaginase therapy. Thirty-five children who received asparaginase 10 000 IU/m 2 i.m. three times weekly for nine doses as part of both multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Twenty-two patients experienced initial allergic reactions to asparaginase during continuation (n = 20) or reinduction (n = 2) phases and 13 children did not exhibit any reaction. An enzyme-linked immunosorbent assay (ELISA) was used to measure anti-asparaginase antibodies in plasma samples, diluted 1:3200, using E. coli asparaginase as the antigen. The median anti-asparaginase antibody concentration (OD at 1:3200 dilution) increased from 0.039 at induction to 0.506 at reinduction in patients who exhibited clinical hypersensitivity (P = 0.0002). By comparison, median antibody level increased from 0.011 to 0.032 OD at identical time points in patients who did not react to asparaginase (P = 0.02). Both post-induction and post-reinduction anti-asparaginase antibody levels were higher in reacting than in nonreacting patients (P = 0.004 and P = 0.01, respectively). Antibody levels were inversely related to the time elapsed between the reaction and sampling (P = 0.011). Although anti-asparaginase antibody levels increased from the post-induction plasma sample to the post-reinduction sample in 28 of 35 patients regardless of whether they exhibited clinical hypersensitivity, patients with hypersensitivity reactions had higher antibody levels than did identically treated control patients at comparable time points in therapy. Therefore, antibody analysis may be of clinical value in predicting future hypersensitivity.

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Section: Figurementioning

confidence: 99%

Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia

et al. 1998

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“…Thus, it is likely that these patients did not have a significantly diminished total L-asparaginase therapeutic effect. 14,15 Pharmacokinetic studies of different L-asparaginase preparations demonstrate that the half-life for the enzyme activity in serum is dependent on the particular enzyme preparation used. 22 The half-life for E. coli L-asparaginase is approximately 1.4 days and for Erwinia L-asparaginase is approximately 0.65 days.…”

Section: Figurementioning

confidence: 99%

“…Thus, it is an acceptable substitute for patients who are allergic to the E. coli protein. [13][14][15] Recently, the Cancer and Leukemia Group B (CALGB) tested a new intensive chemotherapy regimen for adults with untreated ALL. 16 This phase II trial (Study 8811) produced a high rate of complete remissions (85%) and a high proportion of durable remissions in patients from 16 to 80 years old with a median leukemia-free survival (LFS) of 29 months.…”

Section: Introductionmentioning

confidence: 99%

Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia

et al. 1998

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Among its multiple toxic effects, L-asparaginase induces allergic reactions that may reduce its biological effect. The impact of hypersensitivity reactions on the duration of leukemia-free survival (LFS) was assessed in adults with newly diagnosed acute lymphoblastic leukemia (ALL) receiving intensive multi-agent chemotherapy. In CALGB study 8811 (Blood 1995; 85: 2025-2037), 197 adults were scheduled to receive 14 doses of Escherichia coli L-asparaginase (6000 U/m 2 SC) during 7 of the first 12 weeks of chemotherapy. No further L-asparaginase was given. Chemotherapy was given for 24 months. The median follow-up time has been 5.7 years. Of the 141 patients who remained on study after 12 weeks, 82 (58%) had received all 14 planned doses; 38 (27%) had 12-13 L-asparaginase doses documented in their treatment record; 21 (15%) patients had received р11 doses due to a variety of toxic effects. The mean number of doses received prior to experiencing any hypersensitivity reaction was seven (range 1-11). Seven patients had mild hypersensitivity reactions, but all seven eventually received 12-14 doses of E. coli L-asparaginase. Twenty-one other patients had severe hypersensitivity reactions that required discontinuation of E. coli L-asparaginase; 20 of these patients were switched to Erwinia L-asparaginase to complete their treatment. Ultimately, 12 of these 20 patients received 14 doses of L-asparaginase in total, and six received 12-13 doses. Thus, only three of the 21 patients who had severe hypersensitivity reactions received р11 total L-asparaginase doses. Other L-asparaginase-related complications included pancreatitis (15 patients), hypofibrinogenemia Ͻ100 mg/dl (29 patients), and deep venous thrombosis or pulmonary embolism (eight patients); some of these patients had L-asparaginase discontinued after these complications. The estimates for LFS at 3 years were 55% (95% confidence interval, 44-65%) for the patients who received all 14 L-asparaginase doses (median LFS, 5.1 years), 47% (95% CI, 33-62%) for those who received 12-13 doses, and 48% (95% CI, 29-67%) for those who received р11 doses. There were no significant differences between these three groups in the length of LFS (P ‫؍‬ 0.68). LFS did not correlate with a history of severe hypersensitivity reaction (P ‫؍‬ 0.67). In general, E. coli L-asparaginase was well tolerated in these adult patients, and most patients received all of the planned therapy. Patients who had mild L-asparaginase hypersensitivity reactions and patients who switched to Erwinia Lasparaginase because of more severe allergic reactions did not have significantly shorter LFS than the remaining adults treated on this ALL protocol. The possibility that E. coli L-asparaginase is inactivated or destroyed in those individuals who have become hypersensitive to it becomes less important when allergic patients are secondarily treated with Erwinia L-asparaginase.

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“…[7-9] Erwinia asparaginase has been administered to patients who have experienced allergy to native and polyethylene glycosylated (PEG) E coli asparaginase. [5,10-12] However, there are few published reports regarding the pharmacokinetics, tolerability, and long-term outcomes of children who received Erwinia asparaginase after E coli asparaginase allergy. Additionally, the optimal dosing schedule of Erwinia asparaginase after previous E coli asparaginase allergy remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia

Vrooman

Supko

Neuberg

et al. 2009

Pediatric Blood & Cancer

140

110

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Background E coli asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity develops in up to 30% of patients. We assessed the nadir enzyme activity and tolerability of Erwinia asparaginase, an alternative preparation, in E coli asparaginase-allergic patients. Patients and Methods Between 2000-2002, 215 children with newly diagnosed ALL were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 and were to receive 30 weekly doses of intramuscular E coli asparaginase. If E coli asparaginase allergy developed, patients were switched to twice-weekly intramuscular Erwinia asparaginase (25,000 IU/m2). Nadir serum asparaginase activity (NSAA) was measured every 3 weeks. Results Forty-two patients (20%) developed E coli asparaginase allergy and switched to Erwinia. Of 38 patients with evaluable samples, 34 (89%) Erwinia-treated patients had at least one therapeutic NSAA (≥ 0.1 IU/mL). The median NSAA was 0.247 IU/mL 3 days and 0.077 IU/mL 4 days after an Erwinia dose. Associated toxicities included allergy in 14 (33%) and pancreatitis in 3 patients (7%). At a median follow-up of 5.4 years, event-free survival (± standard error) of the 42 patients who switched to Erwinia was 86 ± 5% compared with 81 ± 3% for the 170 patients without E coli asparaginase allergy (p= 0.55). Conclusions Twice-weekly Erwinia asparaginase was well-tolerated and achieved a therapeutically effective NSAA in most E coli-asparaginase allergic patients. Development of E coli allergy and subsequent treatment with twice-weekly Erwinia did not adversely impact event-free survival. Erwinia asparaginase should be considered for E coli asparaginase-allergic patients.

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Therapy with Erwinia l-asparaginase in children with acute leukemia after anaphylaxis to E. coli l-asparaginase

Cited by 29 publications

References 8 publications

Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia

Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia

Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia

Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia

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