Cancer Treatment Reviews
Volume 27, Issue 6 , Pages 339-350 , December 2001

Consolidation therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of cytosine arabinoside, epipodophyllotoxins and cyclophosphamide

  • E.J. Estlin

      Affiliations

    • Department of Paediatric Oncology, Royal Manchester Children's Hospital, Pendlebury, Manchester
    • Correspondence to: Dr E. J. Estlin, Department of Paediatric Oncology, Royal Manchester Children's Hospital, Pendlebury, Manchester M27 4HA, UK. Tel.: 01617272950; Fax: 01617283529; E-mail:eestlin@mch.srht.nwest.nhs.uk
  • ,
  • S.M. Yule

      Affiliations

    • Department of Paediatric Oncology, Royal Hospital for Sick Children, Yorkhill, Glasgow
  • ,
  • S.P. Lowis

      Affiliations

    • Department of Paediatric Oncology, Royal Hospital for Sick Children, St Michael's Hill, Bristol, UK

References 

  1. Chessells JM, Bailey C, Richards SM. Intensification of treatment and survival in all children with lymphoblastic leukaemia: Results of UK Medical Research Council trial UKALL X. Lancet. 1995;345:143–148
  2. Reiter A, Schrappe M, Ludwig W-D, Hiddemann W, Sauter S, Henze G, et al. Chemotherapy in 998 unselected childhood acute lymphoblastic leukaemia patients. Results and conclusions of the multicentre trial ALL-BFM 86. Blood. 1994;84:3122–3133
  3. Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN, et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukaemia and a slow response to initial therapy. N Engl J Med. 1998;338:1663–1671
  4. Niemeyer CM, Reiter A, Riehm H, Donnelly M, Gelber RD, Sallan SE. Comparative results of two intensive treatment programs for acute lymphoblastic leukaemia: The Berlin–Frankfurt–Munster and Dana-Farber Cancer Institute protocols. Ann Oncol. 1991;2:745–749
  5. Land VJ, Shuster JJ, Crist WM, Ravindranath Y, Harris MB, Krance RA, et al. Comparison of two schedules of intermediate-dose methotrexate and cytarabine consolidation for childhood B-precursor acute lymphoblastic leukaemia: A Pediatric Oncology Group Study. J Clin Oncol. 1994;12:1939–1945
  6. Evans WE, Relling M, Rodman JH, Crom WR, Boyett JM, Pui C-H. Conventional compared with individualised chemotherapy for childhood acute lymphoblastic leukaemia. N. Engl J Med. 1998;338:499–505
  7. van Dongen J JM, Seriu T, Panzer-Grumayer ER, Biondi A, Pongers-Willemse MJ, Corral L, et al. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet. 1998;352:1731–1738
  8. Goulden NJ, Knetchli CJ, Garland RJ, Langlands K, Hancock JP, Potter MN, et al. Minimal residual disease analysis for the prediction of relapse in children with standard-risk acute lymphoblastic leukaemia. Br J Haematol. 1998;100:235–244
  9. Chabner BA. Cytidine analogues. In:  Chabner BA,  Longo DL editor. Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia: JB Lippincott Company; 1996;p. 213–234
  10. Wiley JS, Taupin J, Jamieson GP, Snook M, Sawyer WH, Finch LR. Cytosine arabinosaide transport and metabolism in acute leukaemia and T cell lymphoblastic lymphoma. J Clin Invest. 1985;75:632–642
  11. Kufe DW, Spriggs DR. Biochemical and cellular pharmacology of cytosine arabinoside. Semin Oncol. 1985;12:34–48
  12. Crisp LB, Smith SM, Mathers MA, Young GA, Lyons SD, Christopherson RI. Effects of cytosine arabinosie on human leukaemia cells. Int J Biochem Cell Biol. 1996;28:1061–1069
  13. Huang P, Robertson LE, Wright S, Plunkett W. High molecular weight DNA fragmentation: a critical event in nucleoside analogue-induced apoptosis in leukaemia cells. Clin Cancer Res. 1995;1:1005–1013
  14. Kaspers G JL, Pieters R, van Zantwijk CH, De Laat PAJM, De Wall FC, van Wering ER, et al. In vitro drug sensitivity of normal peripheral blood lymphocytes and childhood leukaemic cells form bone marrow and peripheral blood. Br J Cancer. 1991;64:469–474
  15. Plunkett W, Liliemark JO, Adams TM, Nowak B, Estey E, Kantarjian H, et al. Saturation of1-β-D-arabinofuranoylcytosine 5'-triphosphate accumulation in leukaemia cells during high-dose 1-β-D-arabinofuranoylcytosine therapy. Cancer Res. 1987;47:3005–3011
  16. Boos J, Hohenlochter B, Schulze-Westhoff P, Schiller M, Zimmerman M, Creutzig U, et al. Intracellular retention of cytosine arabinoside triphosphate in blast cells from children with acute myelogenous and lymphoblastic leukaemia. Med Pediatr Oncol. 1996;26:397–404
  17. Avramis VI, Biener R, Krailo M, Finklestein J, Ettinger L, Willoughby M, et al. Biochemical pharmacology of high dose 1-β- -arabinofuranosylcytosine in childhood acute leukaemia. Cancer Res. 1987;47:6786–6792
  18. Takemura Y, Kobayashi H, Gibson W, Kimbell R, Miyachi H, Jackman AL. The influence of drug-exposure conditions on the development of resistance to methotrexate or ZD1694 in culture human leukaemia cells. Int J Cancer. 1996;66:29–36
  19. Galpin AJ, Scheutz JD, Mason E, Yanishevski Y, Synold TW, Barredo JC, et al. Differences in folylpolyglutamyl synthase and dihydrofolate reductase expression in human B-lineage versus T-lineage leukaemic lymphoblasts: Mechanisms for lineage differences in methotrexate polyglutamation and cytotoxicity. Mol Pharmacol. 1997;52:155–163
  20. da Silva CP, de Olivera CR, De Lima M. Apoptosis as a mechanism of cell death induced by different chemotherapeutic drugs in human leukaemic T-lymphocytes. Biochem Pharmacol. 1996;51:1331–1340
  21. Klumper E, Pieters R, Veerman AJ, Huismans DR, Loonen AH, Hahlen K, et al. In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukaemia. Blood. 1995;86:3861–3868
  22. Lennard L, Ken D, Lilleyman JS. Oral 6-mercaptopurine in childhood leukaemia: Parent drug pharmacokinetics and active metabolite concentrations. Clin Pharmacol Ther. 1986;40:287–292
  23. Willmore E, Frank AJ, Padget K, Tilby MJ, Austin CA. Etoposide targets topoisomerase IIalpha and IIbeta in leukaemic cells: isoform-specific cleavable complexes visualised and quantified in situ by a novel immunofluorescence technique. Mol Pharmacol. 1998;54:78–85
  24. Cornarotti M, Tinelli S, Willmore E, Fisher LM, Austin CA, Capranico G. Drug sensitivity and sequence specificity of human recombinant DNA topoisomerases II alpha (p170) and II beta (p180). Mol Pharmacol. 1996;50:1463–1471
  25. Long BH, Casazza A-M. Structure-activity relationships of VP-16 analogues. Cancer Chemother Pharmacol. 1994;34:(Suppl): S26–S31
  26. Martins LM, Mesner PW, Kottke TJ, Basi TJ, Sinha S, Tung JS, et al. Comparison of caspase activation and sub-cellular localisation in HL-60 and K562 cells undergoing etoposide-induced apoptosis. Blood. 1997;90:4283–4296
  27. Doyle LA. Topoisomerase expression in cancer cells and clinical samples. Cancer Chemother Pharmacol. 1994;34:S32–S40
  28. Edwards CM, Glisson BS, King CK, Dmallwood-Kentro S, Ross WE. Etoposide-induced DNA cleavage in human leukaemia cells. Cancer Chemother Pharmacol. 1987;20:162–168
  29. Patel S, Austin CA, Fisher LM. Development and properties of an etoposide-resistant human leukaemic CCRF-CEM cell line. Anti Cancer Drug Des. 1990;5:149–157
  30. Ritke MK, Roberts D, Allan WP, Raymond J, Bergoltz VV, Yalowitch JC. Altered stability of etoposide-induced topoisomerase II-DNA complexes in resistant human leukaemia K562 cells. Br J Cancer. 1994;69:687–697
  31. Lowis SP, Newell DR, Pearson A DJ. Exposure and schedule dependency of etoposide in neuroblastoma sand leukaemia cells in vitro. Eur J Cancer. 1995;31A:622–626
  32. Klumper E, Giaccone G, Pieters R, Broekema G, van Ark-Otte J, van Wering ER, et al. Topoisomerase II alpha gene expression in childhood acute lymphoblastic leukaemia. Leukaemia. 1995;9:1653–1660
  33. Den Boer ML, Zwann CM, Pieters R, Kazemier KM, Rottier MM, Flens MJ, et al. Optimal immunocytochemical and flow cytometric detection of P-gp, MRP and LRP in childhood acute lymphoblastic leukaemia. Leukaemia. 1997;11:1078–1085
  34. O'Connor PM, Wassermann K, Sarang M. Relationship between DNA cross-links, cell cycle and apoptosis in Burkitt's lymphoma cell lines differing in sensitivity to nitrogen mustard. Cell Growth Diff. 1991;3:43–52
  35. Bruce WR, Meeker BE, Valeriate FA. Comparison of the sensitivity of normal haematopoetic and transplanted lymphoma colony-forming cells to chemotherapeutic agents administered in vivo. J Nat Cancer Inst. 1966;37:233–245
  36. Sensenbrenner LL, Owens AH, Zawatzky LS, Elfenbein GJ. The comparative effects of selected cytotoxic agents on transplanted haematopoietic cells. Transplantation. 1972;14:347–351
  37. Voelcker G, Wagner T, Wientzek C, Hohorst HJ. Pharmacokinetics of ‘activated’ cyclophosphamide and therapeutic efficacies. Cancer. 1984;54:1179–1186
  38. Teicher BA, Holden SA, Eder JP, Herman TS, Antman KH, Frei E. III. Influence of schedule of alkylating agent cytotoxicity in vitro and in vivo. Cancer Res. 1989;49:5994–5998
  39. Yule SM, Kearns PR, Hall AG. Alkylating agent resistance in paediatric oncology. Int J Pediatr Hematol Oncol. 1997;4:613–628
  40. Harris MB, Shuster JJ, Pullen J, Borowitz MJ, Carroll AJ, Behm FG, et al. Consolidation therapy with antimetabolite-based therapy in standard risk acute lymphoblastic leukaemia of childhood: A Pediatric Oncology Group study. J Clin Oncol. 1998;16:2840–2847
  41. Harris RE, Sather HN, Feig SA. High-dose cytosine arabinoside and L-asparaginase in refractory acute lymphoblastic leukemia: the Children's Cancer Group experience. Med Pediatr Oncol. 1998;30:233–239
  42. Pullen J, Boyett J, Shuster J, Crist W, Land V, Frankel L, et al. Extended triple intrathecal chemotherapy trial for prevention of CNS in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukaemia: A Pediatric Oncology Group Study. J Clin Oncol. 1993;11:839–849
  43. Slevin ML, Piall EM, Aherne GW, Harvey VJ, Johnston A, Lister TA. Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid. J Clin Oncol. 1983;1:546–551
  44. Evans WE, Rodman J, Relling MV, Crom WR, Rivera GK, Crist WM, et al. Individualised dosages of chemotherapy as a strategy to improve response for acute lymphoblastic leukaemia. Semin Hematol. 1991;28:15–21
  45. Avramis VI, Weinberg KI, Sato JK, Lenarsky C, Willoughby ML, Coates TD, et al. Pharmacology studies of 1-β-D-arabinofuranosylcytosine in pediatric patients with leukaemia and lymphoma after a biochemically optimal regimen of loading bolus plus continuous infusion of the drug. Cancer Res. 1989;49:241–247
  46. Periclou AP, Avramis VI. NONMEM population pharmacokinetic studies of cytosine arabinoside after high-dose and after loading bolus followed by continuous infusion of the drug in pediatric patients with leukaemia. Cancer Chemother Pharmacol. 1996;39:42–50
  47. DeAngelis LM, Kreis W, Chan K, Dantis E, Akerman S. Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside. Cancer Chemother Pharmacol. 1992;29:173–177
  48. Takashima Y, Matsuyama K. Pharmacokinetic studies of intermediate-to high-dose 1- beta-D-arabinofuranosylcytosine in children with acute leukaemia and lymphoma. J Clin Pharmacol. 1987;27:330–333
  49. Ho D HW, Frei E. Clinical pharmacology of 1-β-D-arabinofuranosylcytosine. Clin Pharmacol Ther. 1971;12:944
  50. Evans WE, Sinulke JA, Crom WR, Dow L, Look AT, Rivera G. Pharmacokinetics of teniposide (VM26) and etoposide (VP16-213) in children with cancer. Cancer Chemother Pharmacol. 1982;7:147–150
  51. Sinulke JA, Stewart CF, Crom WR, Melton ET, Dahl GV, Evans WE. Teniposide (VM26) disposition in children with leukaemia. Cancer Res. 1984;44:1235–1237
  52. Lowis SP, Price L, Pearson A DJ, Newell DR, Cole M. A study of the feasibility and accuracy of pharmacologically guided etoposide dosing in children. Br J Cancer. 1998;77:2318–2323
  53. Relling MV, Mahmoud HZ, Pui C-H, Sandland JT, Rivera GK, Ribero RC, et al. Etoposide achieves potentially cytotoxic concentrations in the CSF of children with acute lymphoblastic leukaemia. J Clin Oncol. 1996;14:399–404
  54. Amylon MD, Shuster J, Pullen J, Berard B, Link MP, Wharam M, et al. Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T-cell acute lymphoblastic leukaemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group Study. Leukaemia. 1999;13:335–342
  55. Reaman GH, Sposto R, Sensel MG, Lange BJ, Feusner JH, Heerema NA, et al. Treatment outcome and prognostic factors for infants with acute lymphoblastic leukaemia treated on two consecutive trials of the Children's Cancer Group. J Clin Oncol. 1999;17:445–455
  56. Yule SM, Boddy AV, Cole M, Price L, Wyllie R, Tasso MJ, et al. Cyclophosphamide metabolism in children. Cancer Res. 1995;55:803–809
  57. Yule SM, Boddy AV, Cole M, Price L, Wyllie R, Tasso MJ, et al. Cyclophosphamide pharmacokinetics in children. Br J Clin Pharmacol. 1996;41:13–19
  58. Busse D, Busch FW, Bohnenstengel F, Eichelbaum M, Fischer P, Opalinska J, et al. Dose escalation of cyclophosphamide in patients with breast cancer: Consequences for pharmacokinetics and metabolism. J Clin Oncol. 1997;15:1885–1896
  59. Borsi JD, Moe PJ. A comparative study on the pharmacokinetics of methotrexate in a dose range of 0.5g to 33.6g/m2 in children with acute lymphoblastic leukaemia. Cancer. 1987;60:5–13
  60. Evans WE, Crom W, Abromowitch M, Dodge R, Look T, Bowman WP, et al. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukaemia. New Engl J Med. 1986;314:471–477
  61. Donelli MG, Zucchetti M, Robatto A, Perlangeli V, D'Incalci M, Masera G, et al. Pharmacokinetics of HD-MTX in infants, children and adolescents with non-B acute lymphoblastic leukaemia. Med Pediatr Oncol. 1995;24:154–159
  62. Shapiro WR, Young DG, Mehta BM. Methotrexate distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975;293:161–166
  63. Bleyer WA, Dedrick RL. Clinical pharmacology of intrathecal methotrexate. I. Pharmacokinetics in non-toxic patients after lumbar injection. Cancer Treat Rep. 1977;61:703–708
  64. Camitta B, Mahoney D, Leventhal B, Lauer SJ, Shuster JJ, Adair S, et al. Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk Non-T, Non-B acute lymphoblastic leukaemia: A Pediatric Oncology group study. J Clin Oncol. 1994;12:1383–1389
  65. Jacqz-Aigrain E, Nafa S, Medard Y, Bessa E, Lescouer B, Vilmer E. Pharmacokinetics and distribution of 6-mercaptopurine administered intravenously in children with lymphoblastic leukaemia. Eur J Clin Pharmacol. 1997;53:71–74
  66. Howard JP, Albo V, Newton WA. Cytosine arabinoside. Results of a co-operative study in acute childhood leukaemia. Cancer. 1968;21:341–345
  67. Wang JJ, Selawry OS, Vietti TJ, Bodney GP. Prolonged infusion of arabinosylcytosine in childhood leukaemia. Cancer. 1970;25:1–6
  68. Early AP, Priesler HD, Slocum H, Rustum YM. A pilot study of high-dose 1-beta-D-aabinofuranosylcytosine for acute leukaemia and refractory lymphoma: clinical response and pharmacology. Cancer Res. 1982;42:1587–1594
  69. Ochs J, Sinkle JA, Danks MK, Look AT, Bowman WP, Rivera G. Continuous infusion high-dose cytosine arabinoside in refractory childhood leukaemia. J Clin Oncol. 1984;2:1092–1097
  70. Rivera GK, Pui C-H, Dantana VM, Pratt CB, Crist WM. Epipodophyllotoxins in the treatment of childhood cancer. Cancer Chemother Pharmacol. 1994;34:S89–S95
  71. Cavalli F. VP16-213 (Etoposide). A critical review of its activity. Cancer Chemother Pharmacol. 1982;7:81–85
  72. Chard RL, Krivit W, Bleyer WA, Hammond D. Phase II study of VP-16-123 in childhood malignant disease: A Children's Cancer Study Group Report. Cancer Treat Rep. 1979;63:1755–1759
  73. Rosenstock JG, Donaldson MH. Phase I-II trial of VM-26 (NSC-122819) in the treatment of children with late-stage leukaemia. Cancer Treat Rep. 1976;60:265–266
  74. Bleyer WA, Krivit W, Chard RL, Hammond D. Phase II study of VM-26 in acute leukaemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study group. Cancer Treat Rep. 1979;63:977–981
  75. Sweeney M, Tuttle A, Etteldorf J, Whittington GL. Cyclophosphamide in the treatment of common neoplastic diseases of childhood. J Pediatrics. 1962;61:702–708
  76. Fernbach D, Sutow W, Thurman W, Vietti TJ. Clinical evaluation of cyclophosphamide. A new agent for the treatment of children with acute leukaemia. J Am Med Assoc. 1962;182:30–37
  77. Ayash LJ, Wright JE, Tretyakov O, Gonin R, Elias A, Wheeler C, et al. Cyclophosphamide pharmacokinetics: Correlation with cardiac toxicity and tumour response. J Clin Oncol. 1992;10:995–1000
  78. Sullivan MP, Moon TE, Trueworthy R. Combination intrathecal therapy for meningeal leukaemia: Two versus three drugs. Blood. 1997;50:471–479
  79. Pullen J, Boyett J, Shuster J, Crist W, Land V, Frankel L, et al. Extended triple intrathecal chemotherapy trial for prevention of CNS in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukaemia: A Pediatric Oncology Group Study. J Clin Oncol. 1993;11:839–849
  80. Tubergen DG, Gilchrist GS, O'Brien RT, Coccia PF, Sather HN, Waskerwitz MJ, et al. Prevention of CNS disease in intermediate-risk acute lymphoblastic leukaemia: Comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: A Children's Cancer Group Report. J Clin Oncol. 1993;11:520–526
  81. Pui C-H, Mahmoud HH, Rivera GK, Hancock ML, Sandland JT, Behm FG, et al. Early intensification of intrathecal chemotherapy virtually eliminates central nervous system relapse in children with acute lymphoblastic leukaemia. Blood. 1998;92:411–415
  82. Karon M, Freireich E, Frei E. The role of vincristine in the treatment of childhood acute leukaemia. Clinical Pharmacol Ther. 1966;7:332–339
  83. Gaynon PS, Steinberg PG, Bleyer WA, Finklestein JZ, Miller DR, Reaman GH, et al. Association between delivered drug dose and outcome for children with acute lymphoblastic leukaemia and unfavourable presenting features. Med Pediatr Oncol. 1991;19:221–227
  84. Nachman J, Sathe HN, Gaynon PS, Lukens JN, Wolff L, Trigg ME. Augmented Berlin-Frankfurt-Munster Therapy Abrogates the Adverse Prognostic Significance of Slow Early Response to Induction Chemotherapy for Children and Adolescents With Acute Lymphoblastic Leukaemia and Unfavourable Presenting Features: A Report from the Children's Cancer Group. J Clin Oncol. 1997;15:2222–2230
  85. Avramis VI, Wiersma S, Krailo MD, Ramio-Torno LV, Sharpe A, Miu-Mare W, et al. Pharmacokinetic and pharmacodynamic studies of fludarabine and cytosine arabinoside administered as loading boluses followed by continuous infusions after a Phase I/II study in pediatric patients with relapsed leukaemia. Clin Cancer Res. 1985;4:45–52
  86. Winick N, Shuster JJ, Bowman P, Borowitz M, Farrow A, Jacarusa D, et al. Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukaemia. J Clin Oncol. 1996;14:2803–2811
  87. Muller HJ, Boos J. Use of L-asparaginase in childhood ALL. Crit Rev Oncol Hematol. 1998;28:97–113
  88. Hawkins MM, Kinnear Wilson LM, Stovall MA, Marsden HB, Potok M HN, Kingston JE, et al. Epipodophyllotoxins, alkylating agents, and radiation risk of secondary leukaemia after childhood cancer. Br Med J. 1992;304:951–958
  89. Motzer RJ, Gulatt SC, Tong WP, Menendez-Botet C, Lyn P, Mazumdar M, et al. Phase I trial with pharmacokinetic analyses of high-dose carboplatin, etoposide and cyclophosphamide with autologous bone marrow transplantation in patients with refractory germ cell tumours. Cancer Res. 1993;53:3730–3735
  90. Solidozo A, Otero J, Vallejos C, Casanova L, Salas F, Pasco T, et al. Intermittent continuous IV infusion of high-dose cyclophosphamide for remission induction in acute leukaemia. Cancer Treat Rep. 1981;65:213–218
  91. Ciolli S, Leoni F, Caporale R, Salti F, Ferrini PR. Continuous infusion cyclophosphamide plus vincristine cytosine-arabinoside and prednisolone for refractory acute lymphoblastic leukaemia in adults. Haematologica. 1991;76:293–297
  92. Murphy SB, Bowman WP, Abromowitch M, Mirro J, Ochs J, Rivera G, et al. Results of treatment of advanced stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and co-ordinated high-dose methotrexate and cytarabine. J Clin Oncol. 1986;4:1732–1739
  93. Burke G AA, Estlin EJ, Lowis SP. The role of pharmacokinetic and phara odynamic studies in the planning of protocols for the treatment of childhood cancer. Cancer Treat Rev. 1999;25:13–27

PII: S0305-7372(02)90244-6

doi: 10.1053/ctrv.2002.0244

Cancer Treatment Reviews
Volume 27, Issue 6 , Pages 339-350 , December 2001