The Outcome of Children With Acute Lymphoblastic Leukemia Without Receiving Sufficient Dose of L-Asparaginase
,
Abstract
In acute lymphoblastic leukemia (ALL) patients treated with L-asparaginase, discontinuation of the drug occasionally occur due to severe drug complications or resistance, however, due to the high efficacy of this drug in the recovery of patients and the prevention of disease recurrence, resuming the drug regimen is preferred in most patients. What we did in this study was to evaluate and compare the effects of clinical outcomes in the two modes of continuing and discontinuing drug use. In this retrospective cohort study, all children with ALL who had been treated with L-asparaginase during the years 2005 to 2015 were included in the study and categorized into two groups receiving complete treatment regimen (n=160) and those who had to discontinue the drug due to appearing complications (n=9). The rate of relapse and mortality rate was determined and compared across the two groups with a median follow-up time of more than 5 years. 5-yrs Overall survival of all enrolled patients in the groups continued and discontinued was 91.4±2.5% and 71.4±17.1%, respectively (P=0.792). Also, 5-yrs event-free survival of the two groups was 75.8±3.5% and 71.4±17.1%, respectively (P=0.557. Relapse was revealed in 17.5% and 33.3% respectively and mortality in 16.9% and 0.0% (P=0.261). However, the overall prevalence of hypersensitivity reaction to the drug was significantly higher in those patients who discontinued their drug regimen (100% versus 24.4%, P<0.001). Hypersensitivity reaction to drugs may be an important factor in discontinuing L-asparaginase in patients with ALL. The discontinuation of L-asparaginase supplementation due to various complications such as hypersensitivity reactions may be effective in the survival of these patients. However, accurate determination of the effect of discontinuation of this drug on the outcome of children with ALL requires a more comprehensive study with more complicated cases.
2. Pui CH, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital. Blood 2004;104:2690-6.
3. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. New Engl j med 2006;354:166-78.
4. Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001;97:1211-8.
5. Pieters R, Carroll WL. Biology and treatment of acute lymphoblastic leukemia. Hematol Oncol Clin North Am 2010;24:1-18.
6. Duval M, Suciu S, Ferster A, Rialland X, Nelken B, Lutz P, et al. Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial. Blood 2002;99:2734-9.
7. Avramis VI, Tiwari PN. Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. Int j nanomedicine 2006;1:241-54.
8. 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;30:466-72.
9. Pieters R, Hunger SP, Boos J, Rizzari C, Silverman L, Baruchel A, et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer 2011;117:238-49.
10. Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M, 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;13:335-42.
11. Asselin BL, Kreissman S, Coppola DJ, Bernal SD, Leavitt PR, Gelber RD, et al. Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia. J pediatr hematol oncol 1999;21:6-12.
12. 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;96:1709-15.
13. Cheung NK, Chau IY, Coccia PF. Antibody response to Escherichia coli L-asparaginase. Prognostic significance and clinical utility of antibody measurement. Am j pediatr
hematol oncol 1986;8:99-104.
14. Woo MH, Hak LJ, Storm MC, Evans WE, Sandlund JT, Rivera GK, et al. Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia. Leukemia 1998;12:1527-33.
15. Usami I, Imamura T, Takahashi Y, Suenobu SI, Hasegawa D, Hashii Y, et al. Discontinuation of L-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia. Int j hematol 2019;109:477-82.
16. Yen HJ, Chang WH, Liu HC, Yeh TC, Hung GY, Wu KH, et al. Outcomes Following Discontinuation of E. coli l-Asparaginase Upon Severe Allergic Reactions in Children With Acute Lymphoblastic Leukemia. Pediatr blood cancer 2016;63:665-70.
17. Larson RA, Fretzin MH, Dodge RK, Schiffer CA. Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia. Leukemia 1998;12:660-5.
| Files | ||
| Issue | Vol 58, No 3 (2020) | |
| Section | Articles | |
| DOI | https://doi.org/10.18502/acta.v58i3.3773 | |
| Keywords | ||
| Children Acute lymphoblastic leukemia L-asparaginase | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
