Leukemia Research
Volume 26, Issue 8 , Pages 725-730 , August 2002

FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies

Received 24 May 2001 ,Revised 16 November 2001 ,Accepted 4 December 2001.

References 

  1. Cassileth PA, Lynch E, Hines JD, Oken MM, Mazza JJ, Bennet JM, et al.  Varying intensity of postremission therapy in acute myeloid leukemia. Blood. 1992;79:1924
  2. Berman E, Heller G, Santorsa J, McKenzie S, Gee T, Kempin S, et al.  Results of randomised trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood. 1991;77:1666
  3. Wiernick PH, Banks PL, Case DC, Arlin ZA, Periman PO, Todd MB, et al.  Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992;79:313
  4. Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, et al.  A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a southwest oncology group study. Blood. 1996;88:2841
  5. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, et al.  For the cancer and leukemia group B. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N. Engl. J. Med. 1994;331:896
  6. Vogler WR, Velez-Garcı́a E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, et al.  A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogeneous leukemia: a southeastern cancer study group study. J. Clin. Oncol. 1992;10:1103
  7. Keating MJ, Kantarjian H, Smith TL, Estey E, Walters R, Andersson B, et al.  Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J. Clin. Oncol. 1987;7:1071
  8. Davis CL, Rohatiner AZ, Lim J, Whelan JS, Oza AM, Amess J, et al.  The management of recurrent acute myelogenous leukemia at a single centre over a 15 year period. Br. J. Haematol. 1993;83:404
  9. Ho AD, Lipp T, Ehninger G, Illiger H-J, Meyer P, Freund M, et al.  Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia: and active and well-tolerated regimen. J. Clin. Oncol. 1988;6:213
  10. Carella AM, Carlier P, Pungolino E, Resegotti L, Liso V, Stasi R, et al.  Idarubicin in combination with intermediate-dose of cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The Gimema Cooperative Group. Leukemia. 1993;7:196
  11. Kantarjian HM, Estey EH, Keating MJ. Treatment of therapy-related leukemia and myelodisplastic syndrome. Hematol. Oncol. Clin. North Am. 1993;7:81
  12. De Witte T., Suciu S., Peeterman, Fenaux P, Strijckmans P, Hayat M, et al. Intensive chemotherapy for poor prognosis myelodisplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organization for Research and Treatment in Cancer (EORTC-LCG). Leukemia 1995;11:1805.
  13. Invernizzi R, Pecci A, Rossi G, Pelizzari AM, Giusto M, Tinelli C, et al.  Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodisplastic syndromes. Haematologica. 1997;82:660
  14. Bernasconi C, Alessandrino EP, Bernasconi P, Bonfichi M, Lazzarino M, Canevari A, et al.  Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodisplastic syndromes or secondary acute myeloid leukemia evolving from MDS. Br. J. Haematol. 1998;102:678
  15. Estey E, Plunkett W, Gandhi V, Rios MB, Kantarjian H, Keating MJ. Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia. Leuk Lymphoma. 1993;9:343
  16. Visani G, Tosi P, Zinzani PL, Manfroi S, Ottaviani E, Testoni N, et al.  FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of ‘poor risk’ acute myeloid leukemias. Leukemia. 1994;8:1842
  17. Estey E, Thall P, Andreeff M, Beran M, Kantarjian H, O’Brien S, et al.  Use of granulocyte colony-stimulating factor before, during and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodisplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J. Clin. Oncol. 1994;12:671
  18. Clavio M, Carrara P, Miglino M, Pierri I, Canepa L, Balleari E, et al.  High efficacy of fludarabine-containing therapy (FLAG-FLANG) in poor risk acute myeloid leukemia. Haematologica. 1996;8:513
  19. Parker JE, Pagliuca A, Mijobic A, Cullis JO, Czepulkowski B, Rassam SM, et al.  Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia. Br. J. Haematol. 1998;99:939
  20. Estey E, Thall P, Beran M, Kantarjian H, Pierce S, Keating M. Effect of diagnosis (refractory anemia with excess blast, refractory anemia with excess blast in transformation, or acute myeloid leukemia[AML]) on outcome of AML-type chemotherapy. Blood. 1997;90:2969
  21. Ferrara F, Leoni F, Pinto A, Mirto S, Morra E, Zagonel V, et al.  Fludarabine, cytarabine and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes. Cancer. 1999;86:2006
  22. Fleischhack G, Hasan C, Graf N, Mann G, Bode U. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br. J. Haematol. 1998;102:647
  23. Fleischhack G, Graf N, Hasan C, Bode U. Long-term survivors of refractory and relapsed AML of childhood following IDA-FLAG treatment. Blood 2000;96 (Suppl 1):718a.
  24. Byrne JL, Dasgupta E, Pallis M, Turzanski J, Forman K, Mitchell D, et al.  Early allogeneic transplantation for refractory or relapsed acute leukaemia following remission induction with FLAG. Leukemia. 1999;13:786
  25. Jackson G, Taylor P, Smith GM, Marcus R, Smith A, Chu P, et al.  A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blast in transformation. Br. J. Haematol. 2001;112:127
  26. Martı́nez JA, Martı́n G, Sanz GF, Sempere A, Jarque I, De la Rubia J, et al.  A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia. J. Clin. Oncol. 1991;9:39
  27. Larrea L, Martı́nez JA, Sanz GF, Martı́n G, De la Rubia J, Jiménez C, et al.  Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia. Leukemia. 1999;13:161
  28. Sanz MA, Sanz GF, Martı́nez JA, Senent L, Lopez F, Palau J, et al.  Carboplatin alone or in combination in high-risk nonlymphoblastic leukemia. Ann. Oncol. 1992;3(Suppl. 3):S39
  29. Sanz GF, Sanz MA, Vallespı́ T, Cañizo MC, Torrabadella M, Garcia S, et al.  Two regression models and a scoring system for predicting survival and planning treatment in myelodisplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood. 1989;74:395
  30. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al.  International scoring system for evaluating prognosis in myelodisplastic syndromes. Blood. 1997;89:2079
  31. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood. 1998;92:2322
  32. Cancer and Acute Leukemia Group B. Criteria for evaluating acute leukemia for the Leukemia Group B. June 1974 modification of the 1969 criteria. Cancer and Leukemia Group B (CALGB). New York: Scarsdale, 1974.
  33. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207
  34. Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. Am. Stat. Assoc. J. 1958;53:457
  35. Dixon WJ. BMDP Statistical Software. Berkeley, CA: University of California, 1990.
  36. Marie JP, Zittoun R, Sikic BI. Multidrug resistance (MDR1) gene expression in adult acute leukemia: correlation with treatment outcome and in vitro drug sensitivity. Blood. 1991;78:586
  37. Cheson BD, Vena DA, Foss FM, Sorensen JM. Neurotoxicity of purine analogs: a review. J. Clin. Oncol. 1994;12:2216

PII: S0145-2126(02)00003-6

Leukemia Research
Volume 26, Issue 8 , Pages 725-730 , August 2002