Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Clinical hypersensitivity to Escherichia coli asparaginase has been reported to range from 0% to 75%. Throughout the United States, nurses assume frontline responsibility for the assessment of asparaginase-related hypersensitivity reactions. It is essential that nurses educate themselves on the signs and symptoms of asparaginase-related hypersensitivity reactions as well as current supportive care approaches. The purpose of this review is to summarize acute lymphoblastic leukemia and the role of asparaginase and the pathology of allergic reactions. We will also update nurses on the differences in asparaginase preparations including dosing, half-life, rates of hypersensitivity, and routes of administration. A summary of current management and supportive care strategies will be provided as will a discussion of the relationship between allergy, antibodies, and asparaginase activity.
AbbasA. K.LichtmanA. H. (2003). Cellular and molecular immunology (5th ed.). Philadelphia, PA: Saunders.
2.
AsselinB. L. (2012). The right dose for the right patient. Blood, 119, 1617-1618. doi:10.1182/blood-2011-12-395855
3.
AsselinB. L.KreissmanS.CoppolaD. J.BernalS. D.LeavittP. R.GelberR. D.. . .CohenH. J. (1999). Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia. Journal of Pediatric Hematology/Oncology, 21, 6-12. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10029805
4.
AsselinB. L.WhitinJ. C.CoppolaD. J.RuppI. P.SallanS. E.CohenH. J. (1993). Comparative pharmacokinetic studies of three asparaginase preparations. Journal of Clinical Oncology, 11, 1780-1786.
5.
AugustK.MillerW.DaltonS.ShinnickS. (2010, April). Comparison of hypersensitivity reactions to peg-asparaginase in children following intravenous and intramuscular administration. Poster session presented at the meeting of American Society of Pediatric Hematology Oncology, Montreal, Canada.
6.
AvramisV. I.AvramisE. V.HunterW.LongM. C. (2009). Immunogenicity of native or pegylated E. coli and Erwinia asparaginases assessed by ELISA and surface plasmon resonance (SPR-biacore) assays of IgG antibodies (Ab) in sera from patients with acute lymphoblastic leukemia (ALL). Anticancer Research, 29, 299-302.
AvramisV. I.SencerS.PericlouA. P.SatherH.BostromB. C.CohenL. J.HolcenbergJ. S. (2002). A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: A Children’s Cancer Group study. Blood, 99, 1986-1994. doi:10.1182/blood.V99.6.1986
9.
AvramisV. I.TiwariP. N. (2006). Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. International Journal of Nanomedicine, 1, 241-254.
10.
CapizziR. L. (1993). Asparaginase revisited. Leukemia & Lymphoma, 10(s1), 147-150.
11.
CarrollW. L.RaetzE. A. (2012). Clinical and laboratory biology of childhood acute lymphoblastic Leukemia. Journal of Pediatrics, 160, 10-18.
12.
ChenS.-H.PeiD.YangW.ChengC.JehaS.CoxN. J.RellingM. V. (2010). Genetic variations in GRIA1 on chromosome 5q33 related to asparaginase hypersensitivity. Clinical Pharmacology & Therapeutics, 88, 191-196. doi10.1038/clpt.2010.94
13.
DinndorfP. A.GootenbergJ.CohenM. H.KeeganP.PazdurR. (2007). FDA drug approval summary: Pegaspargase (Oncaspar®) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). The Oncologist, 12, 991-998. doi:10.1634/theoncologist.12-8-991
14.
DouerD.De AngeloD. (2008, August). l-Asparaginase mechanism of action. In De AngeloD. (Presenter), New approaches for the treatment of young adults with ALL. Boston, MA: Dana-Farber Cancer Institute, Brigham & Women’s Hospital, Harvard Medical School.
GaynonP. S.AngiolilloA. L.CarrollW. L.NachmanJ. B.TriggM. E.SatherH. N.DevidasM. (2010). Long-term results of the children’s cancer group studies for childhood acute lymphoblastic leukemia 1983-2002: A Children’s Oncology Group Report. Leukemia, 24, 285-297. doi:10.1038/leu.2009.262
17.
GrahamM. L. (2003). Pegaspargase: A review of clinical studies. Advanced Drug Delivery Reviews, 55, 1293-1302. doi:10.1016/S0169-409X(03)00110-8
18.
HungerS., & COG Pharmacy Committee. (2010). Parental and oral chemotherapy administration guidelines used by the Children’s Oncology Group (Version 6). Archives of the Children’s Oncology Group, Acadia, CA.
19.
JehaS.PuiC.-H.RellingM. V.EvansW. E.ChengC.BoyettJ. M.ZhouY. (2007). Total therapy study for XVI for newly diagnosed patients with acute lymphoblastic leukemia. Archives of St. Jude Children’s Research Hospital, Departments of Oncology, Pharmacology Sciences, Infections Diseases, Biostatistics, Pathology, and Radiological Sciences, Memphis, TN.
20.
KangC.XuW.WilsonM.HeB.MillerN. W.BengtenE.CeruttiA. (2009). Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nature Immunology, 10, 889-898. doi:10.1038/ni.1748
21.
KörholzD.WahnU.JürgensH.WahnV. (1990). Allergic reactions in treatment with l-asparaginase: Significance of specific IgE antibodies. Monatsschrift Kinderheilkunde, 138, 23-25.
22.
LiuC.KawediaJ. D.ChengC.PeiD.FernandezC. A.CaiX.RellingM. V. (2012). Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia. Leukemia. Advance online publication. doi:10.1038/leu.2012.102
MasettiR.PessionA. (2009). First-line treatment of acute lymphoblastic leukemia with pegasparaginase. Biologics: Targets & Therapy, 3, 359-368. doi:10.2147/BTT.S3295
25.
Medac Hematology. (2009, November). Standard information for pharmacists-Oncaspar. Wedel, Germany: Author. Retrieved from http://www.medac-sk.eu/file.php?id=124
26.
MoghrabiA.LevyD. E.AsselinB.BarrR.ClavellL.HurwitzC.SilvermanL. B. (2007). Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 5-01 for children with acute lymphoblastic leukemia. Blood, 109, 896-904. doi:10.1182/blood-2006-06-027714
27.
MüllerH. J.BoosJ. (1998). Use of l-asparaginase in childhood ALL. Critical Reviews in Oncology/Hematology, 28, 97-113.
28.
NesbitM.ChardR.EvansA.KaronM.HammondG. D. (1979). Evaluation of intramuscular versus intravenous administration of l-asparaginase in childhood leukemia. American Journal of Pediatric Hematology/Oncology, 1, 9-13.
29.
OhnumaT.HollandJ. F.MeyerP. (1972). Erwinia carotovora asparaginase in patients with prior anaphylaxis to asparaginase from E. coli. Cancer, 30, 376-381.
30.
PaganiM. (2010). The complex clinical picture of presumably allergic side effects to cytostatic drugs: Symptoms, pathomechanism, reexposure, and desensitization. Medical Clinics of North America, 94, 835-852. doi:10.1016/j.mcna.2010.03.002
31.
PanettaJ. C.GajjarA.HijiyaN.HakL. J.ChengC.LiuW.RellingM. V. (2009). Comparison of native E. coli and PEG asparaginase pharmacokinetics and pharmacodynamics in pediatric acute lymphoblastic leukemia. Clinical Pharmacology & Therapeutics, 86, 651-658. doi:10.1038/clpt.2009.162
32.
PanosyanE. H.SeibelN. L.Martin-AragonS.GaynonP. S.AvramisI. A.SatherH.AvramisV. I. (2004). Asparaginase antibody and asparaginase activity in children with higher-risk acute lymphoblastic leukemia. Journal of Pediatric Hematology/Oncology, 26, 217-226. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15087948
33.
PetersenW.ClarkD.SennS.CashT.KellerF.LewG. (2012, April). Pegaspargase administration in children with acute lymphoblastic leukemia. Poster session presented at the meeting of the American Society of Pediatric Hematology Oncology, Montreal, Canada.
34.
PidpartiM.BostromB. (2011). Comparison of allergic reactions to pegasparaginase given intravenously versus intramuscularly. Pediatric Blood & Cancer, 56, 458-459. doi:10.1002/pbc.23380
35.
PietersR.HungerS. P.BoosJ.RizzariC.SilvermanL.BaruchelA.PuiC. H. (2011). l-asparaginase treatment in acute lymphoblastic leukemia: A focus on Erwinia asparaginase. Cancer, 117, 238-249. doi:10.1002/cncr.25489
36.
PuiC. H.CarrollW. L.MeshinchiS.ArceciR. J. (2011). Biology, risk stratification, and therapy of pediatric acute leukemias: An update. Journal of Clinical Oncology, 29, 551-565. doi:10.1200/JCO.2010.30.7405
37.
PuiC. H.EvansW. E. (2006). Treatment of acute lymphoblastic leukemia. New England Journal of Medicine, 354, 166-178.
38.
Sigma-Tau Pharmaceuticals, Inc. (2011, May). Oncaspar (pegaspargase) prescribing information. Gaithersburg, MD. Retrieved from http://www.oncaspar.com/providers.asp
39.
SilvermanL. B.ArmstrongS.CohenL.FlemingM.FletcherJ.GillilandD.WaberD. (2006). DFCI 00-001 Pediatric ALL. Archives of Dana Farber Cancer Institute, Department of Pediatric Leukemia, Boston, MA.
40.
SilvermanL. B.GelberR. D.Kimball DaltonV.AsselinB. L.BarrR. D.ClavellL. A.SallanS. E. (2001). Improved outcome for children with acute lymphoblastic leukemia: Results of Dana-Farber Consortium Protocol 91-01. Blood, 97, 1211-1218. doi:10.1182/blood.V97.5.1211
41.
SilvermanL. B.StevensonK.VroomanL. M.SupkoJ. G.AsselinB.AthaleU.SallanS. E. (2011, December10-13). 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. Paper presented at the 53rd ASH Annual Meeting and Exposition, Atlanta, GA. (Blood, 118, abstract 874)
42.
SompayracL. (2008). How the immune system works (3rd ed.). Malden, MA: Blackwell.
43.
SteinerM.HochreiterD.KasperD. C.KornmüllerR.PichlerH.HaasO. A.AttarbaschiA. (2012). Asparagine and aspartic acid concentrations in bone marrow versus peripheral blood during Berlin-Frankfurt-Münster-based induction therapy for childhood acute lymphoblastic leukemia. Leukemia & Lymphoma, 53, 1682-1687. doi:10.3109/10428194.2012.668681
44.
StockW.DouerD.DeAngeloD. J.ArellanoM.AdvaniA.DamonL.BleyerA. (2011). Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: Recommendations of an expert panel. Leukemia & Lymphoma, 52, 2237-2253. doi:10.3109/10428194.2011.596963
45.
StrulluM.CorradiniN.AudrainM.OrsonneauJ.BouigeD.ThomareP.MéchinaudF. (2010). Silent hypersensitivity to Escherichia coli asparaginase in children with acute lymphoblastic leukemia. Leukemia & Lymphoma, 51, 1464-1472. doi:10.3109/10428194.2010.494316
46.
US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Cancer Therapy Evaluation Program. (2006). Common terminology criteria for adverse events (CTCAE), Version 3.0: Allergy/ Immunology. Retrieved from http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf
47.
US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Cancer Therapy Evaluation Program. (2010). Common terminology criteria for adverse events (CTCAE), Version 4.0: Allergy/Immunology. Retrieved from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
48.
US Department of Health and Human Services, National Institute of Health, National Cancer Institute. (2012). Surveillance epidemiology and end results-SEER stat fact sheets: Acute lymphocytic leukemia. Retrieved from http://seer.cancer.gov/statfacts/html/alyl.html
49.
VroomanL. M.SupkoJ. G.NeubergD. S.AsselinB. L.AthaleU. H.ClavellL.SilvermanL. B. (2010). Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatric Blood & Cancer, 54, 199-205. doi:10.1002/pbc.22225
50.
WadeH. E.ElsworthR.HerbergD.KeppieJ.SargeantK. (1968). A new l-asparaginase with antitumor activity?Lancet, 2, 776-777.
51.
WetzlerM.SanfordB.KurtzbergJ.DeOliveiraD.FrankelS.PowellB.LarsonR. (2007). Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Blood, 109, 4164-4167. doi:10.1182/blood-2006-09-045351
52.
WillerA.GerssJ.KönigT.FrankeD.KühnelH. J.HenzeG.Lanvers-KaminskyC. (2011). 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, 118, 5774-5782. doi:10.1182/blood-2011-07-367904
53.
WooM. H.HakL. J.StormM. C.EvansW. E.SandlundJ. T.RiveraG. K.RellingM. V. (1998). Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia. Leukemia, 12, 1527-1533.
54.
WooM. H.HakL. J.StormM. C.SandlundJ. T.RibeiroR. C.RiveraG. K.RellingM. V. (2000). Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia. Journal of Clinical Oncology, 18, 1525-1532. Retrieved from http://jco.ascopubs.org.proxy.lib.mcw.edu/content/18/7/1525.long
55.
Zalewska-SzewczykB.AndrzejewskiW.MłynarskiW.Jedrychowska-DańskaK.WitasH.BodalskiJ. (2007). The anti-asparagines antibodies correlate with l-asparagines activity and may affect clinical outcome of childhood acute lymphoblastic leukemia. Leukemia & Lymphoma, 48, 931-936. doi:10.1080/10428190701292049
