Asparaginase in the Treatment of Acute Lymphoblastic Leukemia in Adults: Current Evidence and Place in Therapy

References

• Howlader NA, Krapcho M, Miller D, et al. SEER cancer statistics review, 1975–2018; 2021. Available from: https://seer.cancer.gov/csr/1975_2018/. Accessed February 13, 2022.
   Google Scholar
• Boissel N, Auclerc MF, Lhéritier V, et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003;21(5):774–780. doi:10.1200/JCO.2003.02.053
   PubMed Web of Science ®Google Scholar
• de Bont JM, Holt B, Dekker AW, van der Does-van den Berg A, Sonneveld P, Pieters R. Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia. 2004;18(12):2032–2035. doi:10.1038/sj.leu.2403538
   PubMed Web of Science ®Google Scholar
• Hallböök H, Gustafsson G, Smedmyr B, Söderhäll S, Heyman M. Treatment outcome in young adults and children >10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer. 2006;107(7):1551–1561. doi:10.1002/cncr.22189
   PubMed Web of Science ®Google Scholar
• Ramanujachar R, Richards S, Hann I, et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer. 2007;48(3):254–261. doi:10.1002/pbc.20749
   PubMed Web of Science ®Google Scholar
• Ribera JM, Oriol A, Sanz MA, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Español de Tratamiento en Hematología pediatric-based protocol ALL-96. J Clin Oncol. 2008;26(11):1843–1849. doi:10.1200/JCO.2007.13.7265
   PubMed Web of Science ®Google Scholar
• Stock W, La M, Sanford B, et al. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children’s Cancer Group and Cancer and Leukemia Group B studies. Blood. 2008;112(5):1646–1654. doi:10.1182/blood-2008-01-130237
   PubMed Web of Science ®Google Scholar
• Kidd JG. Regression of transplanted lymphomas induced in vivo by means of normal Guinea pig serum. I. Course of transplanted cancers of various kinds in mice and rats given Guinea pig serum, horse serum, or rabbit serum. J Exp Med. 1953;98(6):565–582. doi:10.1084/jem.98.6.565
   PubMed Web of Science ®Google Scholar
• Broome JD. Evidence that the L-asparaginase activity of guinea pig serum is responsible for its antilymphoma effects. Nature. 1961;191(4793):1114–1115. doi:10.1038/1911114a0
   Web of Science ®Google Scholar
• Broome JD. Evidence that the L-asparaginase of Guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of Guinea pig serum in relation to those of the antilymphoma substance. J Exp Med. 1963;118(1):99–120. doi:10.1084/jem.118.1.99
   PubMed Web of Science ®Google Scholar
• Broome JD. Evidence that the L-asparaginase of Guinea pig serum is responsible for its antilymphoma effects. II. Lymphoma 6C3HED cells cultured in a medium devoid of L-asparagine lose their susceptibility to the effects of Guinea pig serum in vivo. J Exp Med. 1963;118(1):121–148. doi:10.1084/jem.118.1.121
   PubMed Web of Science ®Google Scholar
• Ho DH, Whitecar JP Jr, Luce JK, Frei E 3rd. L-asparagine requirement and the effect of L-asparaginase on the normal and leukemic human bone marrow. Cancer Res. 1970;30(2):466–472.
   PubMed Web of Science ®Google Scholar
• Yellin TO, Wriston JC Jr. Antagonism of purified asparaginase from Guinea pig serum toward lymphoma. Science. 1966;151(3713):998–999. doi:10.1126/science.151.3713.998
   PubMed Web of Science ®Google Scholar
• Dolowy WC, Henson D, Cornet J, Sellin H. Toxic and antineoplastic effects of L-asparaginase. Study of mice with lymphoma and normal monkeys and report on a child with leukemia. Cancer. 1966;19(12):1813–1819. doi:10.1002/1097-0142(196612)19:12<1813::AID-CNCR2820191208>3.0.CO;2-E
   PubMed Web of Science ®Google Scholar
• Hill JM, Roberts J, Loeb E, Khan A, MacLellan A, Hill RW. L-asparaginase therapy for leukemia and other malignant neoplasms. Remission in human leukemia. JAMA. 1967;202(9):882–888. doi:10.1001/jama.1967.03130220070012
   PubMed Web of Science ®Google Scholar
• Oettgen HF, Stephenson PA, Schwartz MK, et al. Toxicity of E. coli L-asparaginase in man. Cancer. 1970;25(2):253–278. doi:10.1002/1097-0142(197002)25:2<253::AID-CNCR2820250204>3.0.CO;2-U
   PubMedGoogle Scholar
• Lomelino CL, Andring JT, McKenna R, Kilberg MS. Asparagine synthetase: function, structure, and role in disease. J Biol Chem. 2017;292(49):19952–19958. doi:10.1074/jbc.R117.819060
   PubMed Web of Science ®Google Scholar
• Narta UK, Kanwar SS, Azmi W. Pharmacological and clinical evaluation of L-asparaginase in the treatment of leukemia. Crit Rev Oncol Hematol. 2007;61(3):208–221. doi:10.1016/j.critrevonc.2006.07.009
   PubMed Web of Science ®Google Scholar
• Batool T, Makky EA, Jalal M, Yusoff MM. A comprehensive review on L-Asparaginase and its applications. Appl Biochem Biotechnol. 2016;178(5):900–923. doi:10.1007/s12010-015-1917-3
   PubMed Web of Science ®Google Scholar
• Lubkowski J, Wlodawer A. Structural and biochemical properties of L-asparaginase. Febs J. 2021;288(14):4183–4209. doi:10.1111/febs.16042
   PubMed Web of Science ®Google Scholar
• Ettinger LJ, Kurtzberg J, Voûte PA, Jürgens H, Halpern SL. An open-label, multicenter study of polyethylene glycol-L-asparaginase for the treatment of acute lymphoblastic leukemia. Cancer. 1995;75(5):1176–1181. doi:10.1002/1097-0142(19950301)75:5<1176::AID-CNCR2820750519>3.0.CO;2-Y
   PubMed Web of Science ®Google Scholar
• Heo YA, Syed YY, Keam SJ. Pegaspargase: a review in acute lymphoblastic leukaemia. Drugs. 2019;79(7):767–777. doi:10.1007/s40265-019-01120-1
   PubMed Web of Science ®Google Scholar
• Vrooman LM, Blonquist TM, Stevenson KE, et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11-001. J Clin Oncol. 2021;39(31):3496–3505. doi:10.1200/JCO.20.03692
   PubMed Web of Science ®Google Scholar
• Kloos R, van der Sluis IM, Mastrobattista E, Hennink W, Pieters R, Verhoef JJ. Acute lymphoblastic leukaemia patients treated with PEGasparaginase develop antibodies to PEG and the succinate linker. Br J Haematol. 2020;189(3):442–451. doi:10.1111/bjh.16254
   PubMed Web of Science ®Google Scholar
• Servier Pharmaceuticals. Oncaspar (pegaspargase): US prescribing information; 2021. Available from: http://www.fda.gov. Accessed February 4, 2022.
   Google Scholar
• van der Sluis IM, Vrooman LM, Pieters R, et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016;101(3):279–285. doi:10.3324/haematol.2015.137380
   PubMed Web of Science ®Google Scholar
• Servier Pharmaceuticals. Asparlas (calaspargase pegol): US prescribing information; 2021. Available from: http://www.fda.gov. Accessed February 4, 2022.
   Google Scholar
• Salzer WL, Asselin B, Supko JG, et al. Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children’s Oncology Group. Blood. 2013;122(4):507–514. doi:10.1182/blood-2013-01-480822
   PubMed Web of Science ®Google Scholar
• Maese L, Rizzari C, Coleman R, Power A, van der Sluis I, Rau RE. Can recombinant technology address asparaginase Erwinia chrysanthemi shortages? Pediatr Blood Cancer. 2021;68(10):e29169. doi:10.1002/pbc.29169
   PubMed Web of Science ®Google Scholar
• Jazz Pharmaceuticals. Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn): US prescribing information. Available from: http://www.fda.gov. Accessed February 4, 2022.
   Google Scholar
• Schwartz MK, Lash ED, Oettgen HF, Tomato FA. L-asparaginase activity in plasma and other biological fluids. Cancer. 1970;25(2):244–252. doi:10.1002/1097-0142(197002)25:2<244::AID-CNCR2820250203>3.0.CO;2-V
   PubMedGoogle Scholar
• Henriksen LT, Nersting J, Raja RA, et al. Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia. Br J Haematol. 2014;166(2):213–220. doi:10.1111/bjh.12865
   PubMed Web of Science ®Google Scholar
• Swierczewska M, Lee KC, Lee S. What is the future of PEGylated therapies? Expert Opin Emerg Drugs. 2015;20(4):531–536. doi:10.1517/14728214.2015.1113254
   PubMed Web of Science ®Google Scholar
• Asselin B, Rizzari C. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring. Leuk Lymphoma. 2015;56(8):2273–2280. doi:10.3109/10428194.2014.1003056
   PubMed Web of Science ®Google Scholar
• Asselin BL, Whitin JC, Coppola DJ, Rupp IP, Sallan SE, Cohen HJ. Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol. 1993;11(9):1780–1786. doi:10.1200/JCO.1993.11.9.1780
   PubMed Web of Science ®Google Scholar
• Angiolillo AL, Schore RJ, Devidas M, et al. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children’s Oncology Group Study AALL07P4. J Clin Oncol. 2014;32(34):3874–3882. doi:10.1200/JCO.2014.55.5763
   PubMed Web of Science ®Google Scholar
• Riccardi R, Holcenberg JS, Glaubiger DL, Wood JH, Poplack DG. L-asparaginase pharmacokinetics and asparagine levels in cerebrospinal fluid of rhesus monkeys and humans. Cancer Res. 1981;41(11 Pt 1):4554–4558.
   PubMed Web of Science ®Google Scholar
• Hunger SP, Mullighan CG, Longo DL. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541–1552. doi:10.1056/NEJMra1400972
   PubMed Web of Science ®Google Scholar
• Bender C, Maese L, Carter-Febres M, Verma A. Clinical utility of pegaspargase in children, adolescents and young adult patients with acute lymphoblastic leukemia: a review. Blood Lymphat Cancer. 2021;11:25–40. doi:10.2147/BLCTT.S245210
   PubMed Web of Science ®Google Scholar
• Egler RA, Ahuja SP, Matloub Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother. 2016;7(2):62–71. doi:10.4103/0976-500X.184769
   PubMed Web of Science ®Google Scholar
• Ortega JA, Nesbit ME Jr, Donaldson MH, et al. L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res. 1977;37(2):535–540.
   PubMed Web of Science ®Google Scholar
• Sallan SE, Hitchcock-Bryan S, Gelber R, Cassady JR, Frei E 3rd, Nathan DG. Influence of intensive asparaginase in the treatment of childhood non-T-cell acute lymphoblastic leukemia. Cancer Res. 1983;43(11):5601–5607.
   PubMed Web of Science ®Google Scholar
• Clavell LA, Gelber RD, Cohen HJ, et al. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med. 1986;315(11):657–663. doi:10.1056/NEJM198609113151101
   PubMed Web of Science ®Google Scholar
• Amylon MD, Shuster J, Pullen J, et al. Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study. Leukemia. 1999;13(3):335–342. doi:10.1038/sj.leu.2401310
   PubMed Web of Science ®Google Scholar
• Pession A, Valsecchi MG, Masera G, et al. Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia. J Clin Oncol. 2005;23(28):7161–7167. doi:10.1200/JCO.2005.11.411
   PubMed Web of Science ®Google Scholar
• Abshire TC, Pollock BH, Billett AL, Bradley P, Buchanan GR. Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood. 2000;96(5):1709–1715. doi:10.1182/blood.V96.5.1709
   PubMed Web of Science ®Google Scholar
• Silverman LB, Gelber RD, Dalton VK, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood. 2001;97(5):1211–1218. doi:10.1182/blood.V97.5.1211
   PubMed Web of Science ®Google Scholar
• Larsen EC, Devidas M, Chen S, et al. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children’s Oncology Group Study AALL0232. J Clin Oncol. 2016;34(20):2380–2388. doi:10.1200/JCO.2015.62.4544
   PubMed Web of Science ®Google Scholar
• Winter SS, Dunsmore KP, Devidas M, et al. Improved survival for children and young adults with T-lineage acute lymphoblastic leukemia: results From the Children’s Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018;36(29):2926–2934. doi:10.1200/JCO.2018.77.7250
   PubMed Web of Science ®Google Scholar
• Ram R, Wolach O, Vidal L, Gafter-Gvili A, Shpilberg O, Raanani P. Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric-inspired regimens: systematic review and meta-analysis. Am J Hematol. 2012;87(5):472–478. doi:10.1002/ajh.23149
   PubMed Web of Science ®Google Scholar
• Rijneveld AW, van der Holt B, Daenen SM, et al. Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40. Leukemia. 2011;25(11):1697–1703. doi:10.1038/leu.2011.141
   PubMed Web of Science ®Google Scholar
• Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27(6):911–918. doi:10.1200/JCO.2008.18.6916
   PubMed Web of Science ®Google Scholar
• Thomas X, Boiron JM, Huguet F, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004;22(20):4075–4086. doi:10.1200/JCO.2004.10.050
   PubMed Web of Science ®Google Scholar
• Huguet F, Chevret S, Leguay T, et al. Intensified therapy of acute lymphoblastic leukemia in adults: report of the randomized GRAALL-2005 clinical trial. J Clin Oncol. 2018;36(24):2514–2523. doi:10.1200/JCO.2017.76.8192
   PubMed Web of Science ®Google Scholar
• Storring JM, Minden MD, Kao S, et al. Treatment of adults with BCR-ABL negative acute lymphoblastic leukaemia with a modified paediatric regimen. Br J Haematol. 2009;146(1):76–85. doi:10.1111/j.1365-2141.2009.07712.x
   PubMed Web of Science ®Google Scholar
• Gökbuget N, Beck J, Brandt K, et al. Significant improvement of outcome in Adolescents and Young adults (AYAs) aged 15–35 years with Acute Lymphoblastic Leukemia (ALL) with a pediatric derived adult ALL protocol; results of 1529 AYAs in 2 consecutive trials of the German Multicenter Study Group for adult ALL (GMALL). Blood. 2013;122(21):839.
   Web of Science ®Google Scholar
• Wetzler M, Sanford BL, Kurtzberg J, et al. Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: cancer and Leukemia Group B Study 9511. Blood. 2007;109(10):4164–4167. doi:10.1182/blood-2006-09-045351
   PubMed Web of Science ®Google Scholar
• DeAngelo DJ, Stevenson KE, Dahlberg SE, et al. Long-term outcome of a pediatric-inspired regimen used for adults aged 18–50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2015;29(3):526–534. doi:10.1038/leu.2014.229
   PubMed Web of Science ®Google Scholar
• Toft N, Birgens H, Abrahamsson J, et al. Results of NOPHO ALL2008 treatment for patients aged 1–45 years with acute lymphoblastic leukemia. Leukemia. 2018;32(3):606–615. doi:10.1038/leu.2017.265
   PubMed Web of Science ®Google Scholar
• Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019;133(14):1548–1559. doi:10.1182/blood-2018-10-881961
   PubMed Web of Science ®Google Scholar
• Advani AS, Larsen E, Laumann K, et al. Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia. Blood Adv. 2021;5(2):504–512. doi:10.1182/bloodadvances.2020002439
   PubMed Web of Science ®Google Scholar
• Geyer MB, Ritchie EK, Rao AV, et al. Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia. Haematologica. 2021;106(8):2086–2094. doi:10.3324/haematol.2020.251686
   PubMed Web of Science ®Google Scholar
• Rytting ME, Thomas DA, O’Brien SM, et al. Augmented Berlin-Frankfurt-Münster therapy in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL). Cancer. 2014;120(23):3660–3668. doi:10.1002/cncr.28930
   PubMed Web of Science ®Google Scholar
• Thomas DA, O’Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol. 2010;28(24):3880–3889. doi:10.1200/JCO.2009.26.9456
   PubMed Web of Science ®Google Scholar
• Maury S, Chevret S, Thomas X, et al. Rituximab in B-lineage adult acute lymphoblastic leukemia. N Engl J Med. 2016;375(11):1044–1053. doi:10.1056/NEJMoa1605085
   PubMed Web of Science ®Google Scholar
• Stock W, Douer D, DeAngelo DJ, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma. 2011;52(12):2237–2253. doi:10.3109/10428194.2011.596963
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. Acute lymphoblastic leukemia (version 4.2021). Available from: https://www.nccn.org. Accessed February 13, 2022.
   Google Scholar
• Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020;135(13):987–995. doi:10.1182/blood.2019002132
   PubMed Web of Science ®Google Scholar
• Burke PW, Hoelzer D, Park JH, Schmiegelow K, Douer D. Managing toxicities with asparaginase-based therapies in adult ALL: summary of an ESMO Open-Cancer Horizons roundtable discussion. ESMO Open. 2020;5(5):e000858. doi:10.1136/esmoopen-2020-000858
   PubMed Web of Science ®Google Scholar
• Schmiegelow K, Rank CU, Stock W, Dworkin E, van der Sluis I. SOHO state of the art updates and next questions: management of asparaginase toxicity in adolescents and young adults with acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2021;21(11):725–733. doi:10.1016/j.clml.2021.07.009
   PubMed Web of Science ®Google Scholar
• Aldoss I, Douer D, Behrendt CE, et al. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia. Eur J Haematol. 2016;96(4):375–380. doi:10.1111/ejh.12600
   PubMed Web of Science ®Google Scholar
• Burke PW, Aldoss I, Lunning MA, et al. Pegaspargase-related high-grade hepatotoxicity in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not predict recurrent hepatotoxicity with subsequent doses. Leuk Res. 2018;66:49–56. doi:10.1016/j.leukres.2017.12.013
   PubMed Web of Science ®Google Scholar
• Bodmer M, Sulz M, Stadlmann S, Droll A, Terracciano L, Krähenbühl S. Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with L-asparaginase. Digestion. 2006;74(1):28–32. doi:10.1159/000095827
   PubMed Web of Science ®Google Scholar
• Al-Nawakil C, Willems L, Mauprivez C, et al. Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors. Leuk Lymphoma. 2014;55(7):1670–1674. doi:10.3109/10428194.2013.845886
   PubMed Web of Science ®Google Scholar
• Alshiekh-Nasany R, Douer D. L-carnitine for treatment of pegasparaginase-induced hepatotoxicity. Acta Haematol. 2016;135(4):208–210. doi:10.1159/000442342
   PubMed Web of Science ®Google Scholar
• Arora S, Klair J, Bellizzi AM, Tanaka T. L-carnitine and vitamin B complex for PEG-L-asparaginase-induced hepatotoxicity. ACG Case Rep J. 2019;6(8):e00194. doi:10.14309/crj.0000000000000194
   PubMed Web of Science ®Google Scholar
• Blackman A, Boutin A, Shimanovsky A, Baker WJ, Forcello N. Levocarnitine and vitamin B complex for the treatment of pegaspargase-induced hepatotoxicity: a case report and review of the literature. J Oncol Pharm Pract. 2018;24(5):393–397. doi:10.1177/1078155217710714
   PubMed Web of Science ®Google Scholar
• Lu G, Karur V, Herrington JD, Walker MG. Successful treatment of pegaspargase-induced acute hepatotoxicity with vitamin B complex and L-carnitine. Proc. 2016;29(1):46–47. doi:10.1080/08998280.2016.11929355
   Google Scholar
• Schulte R, Hinson A, Huynh V, et al. Levocarnitine for pegaspargase-induced hepatotoxicity in older children and young adults with acute lymphoblastic leukemia. Cancer Med. 2021;10(21):7551–7560. doi:10.1002/cam4.4281
   PubMed Web of Science ®Google Scholar
• Trang E, Ngo D, Chen J, Aldoss I, Salhotra A, Pullarkat V. Levocarnitine for pegasparaginase-induced hepatotoxicity in acute lymphoblastic leukemia. Leuk Lymphoma. 2020;61(13):3161–3164. doi:10.1080/10428194.2020.1805108
   PubMed Web of Science ®Google Scholar
• Sudour H, Schmitt C, Contet A, Chastagner P, Feillet F. Acute metabolic encephalopathy in two patients treated with asparaginase and ondasetron. Am J Hematol. 2011;86(3):323–325. doi:10.1002/ajh.21964
   PubMed Web of Science ®Google Scholar
• Tong WH, Pieters R, de Groot-Kruseman HA, et al. The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia. Haematologica. 2014;99(11):1716–1721. doi:10.3324/haematol.2014.109413
   PubMed Web of Science ®Google Scholar
• Beziat G, Tavitian S, Picard M, Faguer S, Recher C, Huguet F. Multiple severe toxicities of L-asparaginase and their innovative management during induction therapy of acute lymphoblastic leukemia in an adult patient. Case Rep Hematol. 2019;2019:9086570. doi:10.1155/2019/9086570
   PubMed Web of Science ®Google Scholar
• Burke MJ, Rheingold SR. Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia. Leuk Lymphoma. 2017;58(3):540–551. doi:10.1080/10428194.2016.1213826
   PubMed Web of Science ®Google Scholar
• Burke MJ, Devidas M, Maloney K, et al. Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children’s oncology group (COG) clinical trials. Leuk Lymphoma. 2018;59(7):1624–1633. doi:10.1080/10428194.2017.1397658
   PubMed Web of Science ®Google Scholar
• Beaupin LK, Bostrom B, Barth MJ, et al. Pegaspargase hypersensitivity reactions: intravenous infusion versus intramuscular injection - a review. Leuk Lymphoma. 2017;58(4):766–772. doi:10.1080/10428194.2016.1218004
   PubMed Web of Science ®Google Scholar
• Li RJ, Jin R, Liu C, et al. FDA approval summary: calaspargase Pegol-mknl for treatment of acute lymphoblastic leukemia in children and young adults. Clin Cancer Res. 2020;26(2):328–331. doi:10.1158/1078-0432.CCR-19-1255
   PubMed Web of Science ®Google Scholar
• Plourde PV, Jeha S, Hijiya N, et al. Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial. Pediatr Blood Cancer. 2014;61(7):1232–1238. doi:10.1002/pbc.24938
   PubMed Web of Science ®Google Scholar
• Vrooman LM, Supko JG, Neuberg DS, et al. Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2010;54(2):199–205. doi:10.1002/pbc.22225
   PubMed Web of Science ®Google Scholar
• Cooper SL, Young DJ, Bowen CJ, Arwood NM, Poggi SG, Brown PA. Universal premedication and therapeutic drug monitoring for asparaginase-based therapy prevents infusion-associated acute adverse events and drug substitutions. Pediatr Blood Cancer. 2019;66(8):e27797. doi:10.1002/pbc.27797
   PubMed Web of Science ®Google Scholar
• McCormick M, Lapinski J, Friehling E, Smith K. Premedication prior to peg-asparaginase is cost-effective for pediatric leukemia patients. Blood. 2020;136(Supplement 1):7. doi:10.1182/blood-2020-134749
   Web of Science ®Google Scholar
• Salzer W, Bostrom B, Messinger Y, Perissinotti AJ, Marini B. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59(8):1797–1806. doi:10.1080/10428194.2017.1386305
   PubMed Web of Science ®Google Scholar
• Daley RJ, Rajeeve S, Kabel CC, et al. Tolerability and toxicity of pegaspargase in adults 40 years and older with acute lymphoblastic leukemia. Leuk Lymphoma. 2021;62(1):176–184. doi:10.1080/10428194.2020.1824068
   PubMed Web of Science ®Google Scholar
• Finch ER, Smith CA, Yang W, et al. Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia. Pediatr Blood Cancer. 2020;67(1):e28040. doi:10.1002/pbc.28040
   PubMed Web of Science ®Google Scholar
• Zwicker JI, Wang T-F, DeAngelo DJ, et al. The prevention and management of asparaginase-related venous thromboembolism in adults: guidance from the SSC on Hemostasis and Malignancy of the ISTH. J Thromb Haemost. 2020;18(2):278–284. doi:10.1111/jth.14671
   PubMed Web of Science ®Google Scholar
• Grace RF, Dahlberg SE, Neuberg D, et al. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols. Br J Haematol. 2011;152(4):452–459. doi:10.1111/j.1365-2141.2010.08524.x
   PubMed Web of Science ®Google Scholar
• Grace RF, DeAngelo DJ, Stevenson KE, et al. The use of prophylactic anticoagulation during induction and consolidation chemotherapy in adults with acute lymphoblastic leukemia. J Thromb Thrombolysis. 2018;45(2):306–314. doi:10.1007/s11239-017-1597-7
   PubMed Web of Science ®Google Scholar
• Haskell CM, Canellos GP, Leventhal BG, et al. L-asparaginase: therapeutic and toxic effects in patients with neoplastic disease. N Engl J Med. 1969;281(19):1028–1034. doi:10.1056/NEJM196911062811902
   PubMed Web of Science ®Google Scholar
• Hill JM, Loeb E, MacLellan A, et al. Response to highly purified L-asparaginase during therapy of acute leukemia. Cancer Res. 1969;29(8):1574–1580.
   PubMed Web of Science ®Google Scholar
• Shaw MT, Barnes CC, Madden FJ, Bagshawe KD. L-asparaginase and pancreatitis. Lancet. 1970;2(7675):721. doi:10.1016/S0140-6736(70)91990-2
   PubMed Web of Science ®Google Scholar
• Wolthers BO, Frandsen TL, Baruchel A, et al. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study. Lancet Oncol. 2017;18(9):1238–1248. doi:10.1016/S1470-2045(17)30424-2
   PubMed Web of Science ®Google Scholar
• Douer D, Aldoss I, Lunning MA, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905–911. doi:10.1200/JCO.2013.50.2708
   PubMed Web of Science ®Google Scholar
• Oparaji JA, Rose F, Okafor D, et al. Risk factors for asparaginase-associated pancreatitis: a systematic review. J Clin Gastroenterol. 2017;51(10):907–913. doi:10.1097/MCG.0000000000000827
   PubMed Web of Science ®Google Scholar
• Grimes AC, Chen Y, Bansal H, et al. Genetic markers for treatment-related pancreatitis in a cohort of Hispanic children with acute lymphoblastic leukemia. Support Care Cancer. 2021;29(2):725–731. doi:10.1007/s00520-020-05530-w
   PubMed Web of Science ®Google Scholar
• Wang J, Cheng S, Hu L, Huang T, Huang Z, Hu S. Association of asparaginase-associated pancreatitis and ULK2 gene polymorphism. Int J Clin Exp Pathol. 2020;13(3):347–356.
   PubMed Web of Science ®Google Scholar
• Wolthers BO, Frandsen TL, Patel CJ, et al. Trypsin-encoding PRSS1-PRSS2 variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report. Haematologica. 2019;104(3):556–563. doi:10.3324/haematol.2018.199356
   PubMed Web of Science ®Google Scholar
• Sakaguchi S, Higa T, Suzuki M, Fujimura J, Shimizu T. Prophylactic use of octreotide for asparaginase-induced acute pancreatitis. Int J Hematol. 2017;106(2):266–268. doi:10.1007/s12185-017-2219-z
   PubMed Web of Science ®Google Scholar
• Lin T, Hernandez-Illas M, Rey A, et al. A randomized Phase I study to evaluate the safety, tolerability, and pharmacokinetics of recombinant erwinia asparaginase (JZP-458) in healthy adult volunteers. Clin Transl Sci. 2021;14(3):870–879. doi:10.1111/cts.12947
   PubMed Web of Science ®Google Scholar
• Maese L, Rau RE, Raetz EA, et al. 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. J Clin Oncol. 2020;38(15_suppl):TPS7568–TPS7568. doi:10.1200/JCO.2020.38.15_suppl.TPS7568
   Web of Science ®Google Scholar
• Maese L, Loh ML, Lin T, et al. Initial results from a Phase 2/3 study of recombinant erwinia asparaginase (JZP458) in patients with Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL) who are allergic/hypersensitive to E. coli-derived asparaginases. Blood. 2021;138(Supplement 1):2307. doi:10.1182/blood-2021-147023
   PubMed Web of Science ®Google Scholar
• Bertrand Y, Baruchel A, Thomas XG, et al. Clinical activity of ERY001 (erythrocyte encapsulated l-asparaginase) and native l-asparaginase (L-ASP) in combination with COOPRALL regimen in phase III randomized trial in patients with relapsed acute lymphoblastic leukemia (ALL). J Clin Oncol. 2015;33(15_suppl):7004. doi:10.1200/jco.2015.33.15_suppl.7004
   Web of Science ®Google Scholar
• Lynggaard LS, Gottschalk Højfeldt S, Moeller L, et al. NOR-GRASPALL2016 (NCT03267030): asparaginase encapsulated in erythrocytes (eryaspase) - a promising alternative to peg-asparaginase in case of hypersensitivity. Blood. 2020;136(Supplement 1):13–14. doi:10.1182/blood-2020-139373
   Web of Science ®Google Scholar
• Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125(14):2474–2487. doi:10.1002/cncr.32116
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–753. doi:10.1056/NEJMoa1509277
   PubMed Web of Science ®Google Scholar
• Alliance for Clinical Trials in Oncology. Inotuzumab ozogamicin and frontline chemotherapy in treating young adults with newly diagnosed B acute lymphoblastic leukemia. Available from: https://clinicaltrials.gov/ct2/show/NCT03150693. Accessed February 13, 2022.
   Google Scholar
• Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–847. doi:10.1056/NEJMoa1609783
   PubMed Web of Science ®Google Scholar
• Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522–1531. doi:10.1182/blood-2017-08-798322
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, DeAngelo DJ, Advani AS, et al. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017;4(8):e387–e398. doi:10.1016/S2352-3026(17)30103-5
   PubMed Web of Science ®Google Scholar
• Rousselot P, Coudé MM, Gokbuget N, et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood. 2016;128(6):774–782. doi:10.1182/blood-2016-02-700153
   PubMed Web of Science ®Google Scholar
• Patel B, Kirkwood AA, Dey A, et al. Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial. Leukemia. 2017;31(1):58–64. doi:10.1038/leu.2016.219
   PubMed Web of Science ®Google Scholar
• Kloos RQH, Pieters R, Jumelet FMV, de Groot-Kruseman HA, van den Bos C, van der Sluis IM. Individualized asparaginase dosing in childhood acute lymphoblastic leukemia. J Clin Oncol. 2020;38(7):715–724. doi:10.1200/JCO.19.02292
   PubMed Web of Science ®Google Scholar
• Kloos RQH, Mathôt R, Pieters R, van der Sluis IM. Individualized dosing guidelines for PEGasparaginase and factors influencing the clearance: a population pharmacokinetic model. Haematologica. 2021;106(5):1254–1261. doi:10.3324/haematol.2019.242289
   PubMed Web of Science ®Google Scholar
• Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010;376(9757):2009–2017. doi:10.1016/S0140-6736(10)62002-8
   PubMed Web of Science ®Google Scholar
• Barredo JC, Devidas M, Lauer SJ, et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study. J Clin Oncol. 2006;24(19):3142–3149. doi:10.1200/JCO.2005.03.3373
   PubMed Web of Science ®Google Scholar
• Truelove E, Fielding AK, Hunt BJ. The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia. Leukemia. 2013;27(3):553–559. doi:10.1038/leu.2012.290
   PubMed Web of Science ®Google Scholar