Mathematical model to predict methotrexate elimination in children with acute lymphoblastic leukemia

Open access

Abstract

Introduction: Methotrexate, a structural analogue to the folic acid, is one of the most frequently used antimetabolites in pediatric oncologic pathology. Its mode of action and toxic effects are now well known. Material

and method: Our study aimed to describe the quantitation of the drug in serum of 40 children with acute lymphatic leukemia receiving high doses of methotrexate and to predict serum methotrexate levels at 96 hours, based on 48 h, 72h levels and on alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine serum levels. The above mentioned parameters were analyzed by sampling serum levels at 48h, 72h and 96 hours after methotrexate administration and a logical regression model being projected upon obtained results. Results and conclusions: methotrexate serum level at 96 hours does not depend on either AST, ALT, urea, creatinine levels or on the methotrexate level determined at 48 hours, it only depends on the methotrexate serum level at 72 hours.

1. Kamps WA, van der Pal-de Bruin KM, Veerman AJ, Fiocco M, Bierings M, Pieters R. Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004. Leukemia. 2010;24(2):309-19 DOI: 10.1038/ leu.2009.258

2. Kampen KR. The discovery and early understanding of leukemia. Leuk Res. 2012;36(1):6-13. DOI: 10.1016/j. leukres.2011.09.028

3. Mantadakis E, Cole PD, Kamen BA. High-dose methotrexate in acute lymphoblastic leukemia: where is the evidence for its continued use? Pharmacotherapy. 2005;25(5):748-55. DOI: 10.1592/phco.25.5.748.63584

4. Sterba J, Valík D, Bajciová V, Kadlecová V, Gregorová V, Mendelová D. High-dose methotrexate and/or leucovorin rescue for the treatment of children with lymphoblastic malignancies: do we really know why, when and how? Neoplasma. 2005;52(6):456-63.

5. Silverman LB, Stevenson KE, O’Brien JE, Asselin BL, Barr RD, Clavell L et al.: Long-term results of Dana- Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000). Leukemia. 2010;24(2):320-34. DOI: 10.1038/leu.2009.253

6. Veerman AJ, Hählen K, Kamps WA, Van Leeuwen EF, De Vaan GA, Solbu G, et al. High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group. J Clin Oncol. 1996;14(3):911-8.

7. Salzer WL, Devidas M, Carroll WL, Winick N, Pullen J, Hunger SP et al. Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984-2001: a report from the Children’s Oncology Group. Leukemia. 2010;24(2):355-70. DOI: 10.1038/leu.2009.261

8. Pui CH, Pei D, Sandlund JT, Ribeiro RC, Rubnitz JE, Raimondi SC et al. Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia. Leukemia. 2010;24(2):371-82. DOI: 10.1038/leu.2009.252

9. Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, et al. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Blood. 2011;118(2):243-51. DOI: 10.1182/ blood-2010-12-322909

10. Mahoney DH Jr, Shuster JJ, Nitschke R, Lauer S, Steuber CP, Camitta B. Intensification with intermediate- dose intravenous methotrexate is effective therapy for children with lower-risk B-precursor acute lymphoblastic leukemia: A Pediatric Oncology Group study. J Clin Oncol. 2000;18(6):1285-94.

11. Schmiegelow K, Forestier E, Hellebostad M, Heyman M, Kristinsson J, Soderhall S et al. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia. Leukemia. 2010;24(2):345-54. DOI: 10.1038/leu.2009.251

12. Mitchell C, Richards S, Harrison CJ, Eden T. Long-term follow-up of the United Kingdom medical research council protocols for childhood acute lymphoblastic leukaemia, 1980-2001. Leukemia. 2010;24(2):406-18. DOI: 10.1038/leu.2009.256

13. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. New Engl J Med. 1998;338(8):499-505. DOI: 10.1056/NEJM199802193380803

14. Mahoney DH, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP, et al. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower- risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III Trial. J Clin Oncol. 1998;16(1):246-54.

15. Camitta B, Mahoney D, Leventhat B, Lauer SJ, Shuster JJ, Adair S, et al. Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: a Pediatric Oncology Group study. J Clin Oncol. 1994;12(7):1383-9.

16. Camitta B, Leventhal B, Lauer S, Shuster JJ, Adair S, Casper J, et al. Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol. 1989;7(10):1539-44.

17. Möricke A, Zimmermann M, Reiter A, Henze G, Schrauder A, Gadner H et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010;24(2):265-84. DOI: 10.1038/leu.2009.257

18. Ahmed YA, Hasan Y. Prevention and Management of High Dose Methotrexate Toxicity. J Cancer Sci Ther 2013;5(3):106-12. DOI: 10.4172/1948-5956.1000193

19. Le Guellec C, Blasco H, Benz J, Hulin A. Therapeutic drug monitoring of methotrexate after its administrations in high-dose protocols. Therapie. 2010;65(3):163-9. DOI: 10.2515/therapie/2010016

20. Perazella MA, Moeckel GW. Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy. Semin Nephrol. 2010;30(6):570-81. DOI: 10.1016/j.semnephrol. 2010.09.005

21. Evans WE, Crom WR, Abromowitch M, Dodge R, Look AT, Bowman P, et al. Clinical pharmacodynamics of high-dose methotrexate in childhood acute lymphocytic leukemia. Identification of a relation between concentration and effect. New Engl J Med. 1986;314(8):471-7. DOI: 10.1056/NEJM198602203140803

22. Panetta JC, Wall A, Pui CH, Relling MV, Evans WE. Methotrexate Intracellular Dispositionin Acute Lymphoblastic Leukemia.A Mathematical model of γ-Glutamyl Hydrolase Activity. Clin Cancer Res. 2002;8(7):2423-9.

23. Asselin BL, Devidas M, Wang C, Pullen J, Borowitz MJ, Hutchinson R et al. Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children’s Oncology Group (POG 9404). Blood. 2011;118(4):874-83. DOI: 10.1182/ blood-2010-06-292615

24. Bertino JR, Goker E, Gorlick R, Li WW, Banerjee D. Resistance mechanisms to methotrexate in tumors. Oncologist. 1996;1(4):223-6.

25. Matherly LH, Taub JW. Methotrexate pharmacology and resistance in childhood acute lymphoblastic leukemia. Leuk Lymphoma. 1996;21(5-6):359-68. DOI: 10.3109/10428199609093433

26. Gorlick R, Goker E, Trippett T, Watham M, Banerjee D, Bertino JR. Intrinsic and acquired resistance to methotrexate in acute leukemia. New Engl J Med. 1996;335(14):1041-8. DOI: 10.1056/ NEJM199610033351408

27. Farrow AC, Buchanan GR, Zwiener RJ, Bowman WP, Winick NJ. Serum aminotransferase elevation during and following treatment of childhood acute lymphoblastic leukemia. J Clin Oncol. 1997;15(4):1560-6.

28. Moe PJ, Holen A.: High-dose methotrexate in childhood acute lymphoblastic leukemia. Pediatr Hematol Oncol 2000;17(8):615-22. DOI: 10.1080/08880010050211321

29. Maiquma T, Hayashi Y, Ueshima S, Kaji M, Eqawa T, Chayama T, et al. Relationship between oral mucositis and high-dose methotrexate in pediatric acute lymphoblastic leukemia. Int J Clin Pharmacol Ther. 2008;46(11):584-90. DOI: 10.5414/CPP46584

30. Xu WQ, Tang YM, Fanq CQ, Song H, Shi SW, Yang SL, et al. Study on elimination delay in high-dose methotrexate in children with acute lymphoblastic leukemia. Zhonghua Xue Ye Xue Za Zhi. 2005;26(1):15-8.

31. Isoda T, Ito S, Kajiwara M, Nagasawa M. Successful high-dose methotrexate therapy in a patient with acute lymphoblastic leukemia who developed acute renal failure during initial treatment. Pediatr Int. 2007;49(6):1018-9. DOI: 10.1111/j.1442-200X.2007.02461.x

32. Perez-Verdia A, Angulo F, Hardwicke FL, Nugent KM. Acute cardiac toxicity associated with high-dose intravenous methotrexate therapy: case report and review of the literature. Pharmacotherapy. 2005:25(9):1271-6. DOI: 10.1592/phco.2005.25.9.1271

33. Joannon P, Oviedo I, Campbell M, Tordecilla J. High dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance. Pediatr Blood Cancer. 2004;43(1):17-22. DOI: 10.1002/ pbc.20032

34. Borsi JD, Moe PJ. Systemic Clearance of Methotrexate in the Prognosis of Acute Lymphoblastic Leukemia in Children. Cancer. 1987;60(12):3020-4. DO I:2/1097-0142(19871215)60:12<3020::AID-CNCR2820601227> 3.0.CO;2-0

35. Hein DW, Doll MA. Accuracy of various NAT 2 SNP genotyping panelsto infer rapid, intermediateand slow acetylator phenotypes. Pharmacogenomics. 2012;13(1):31-41. DOI: 10.2217/pgs.11.122

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information


IMPACT FACTOR 2017: 0.400
5-year IMPACT FACTOR: 0.320



CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2017: 0.144
Source Normalized Impact per Paper (SNIP) 2017: 0.195

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1387 1387 635
PDF Downloads 1884 1884 885