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Pediatr Blood Cancer. 2016 Feb;63(2):228-33. doi: 10.1002/pbc.25757. Epub 2015 Sep 16.

Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia.

Author information

1
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.
2
Division of Oncology, Children's Hospital of Orange County, Orange, California.
3
Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
4
Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
5
Ann & Robert H. Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, Chicago, Illinois.
6
Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
7
Department of Pediatric Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
8
Pediatric Hematology-Oncology, Children's Hospitals & Clinics of Minnesota, Minneapolis, Minnesota.
9
Division of Hematology/Oncology, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
10
Department of Hematology-Oncology, All Children's Hospital, St. Petersburg, Florida.
11
Center for Cancer & Blood Disorders, Children's Hospital Colorado, Aurora, Colorado.
12
Jazz Pharmaceuticals, Palo Alto, California.
13
Formerly of Jazz Pharmaceuticals, Palo Alto, California.

Abstract

BACKGROUND:

Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase.

PATIENTS AND METHODS:

Between 2012 and 2013, 30 patients (age 1-17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥ 0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥ 0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities.

RESULTS:

Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥ 0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63-95%) 48 hr post-dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22-66%) 72 hr post-dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%.

CONCLUSIONS:

IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (≥ 0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01643408.

KEYWORDS:

Erwinia asparaginase; acute lymphoblastic leukemia; childhood ALL; clinical trials; pharmacokinetics

PMID:
26376459
PMCID:
PMC4715717
DOI:
10.1002/pbc.25757
[Indexed for MEDLINE]
Free PMC Article

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