Abstract
The purpose of the present study was to evaluate the use of the FLAG regimen (fludarabine phosphate in combination with cytosine arabinoside and granulocyte colony stimulating factor (GCSF) in patients with poor risk myeloid malignancy. The rationale for this combination is based on the synergy between fludarabine phosphate and cytosine arabinoside; the cytotoxic activity of cytosine arabinoside is dependent on its intracellular conversion to its active metabolite the 5′-triphosphate (ara-CTP). The intracellular accumulation of ara-CTP is a multistep process, of which phosporylation of ara-C to its monophosphate by deoxycytidine kinase (Cyd kinase) is the rate-limiting event. Fludarabine phosphate increases the activity of this critical enzyme leading to a higher rate of araCTP accumulation intracellularly (Gandhi
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Gandhi V, Plunkett W (1988) Modulation of arabinosyl nucleoside metabolism by arabinosylnucleotides in human leukemia cells. Cancer Res 48: 329–334
Tafuri A, Andreeff M (1990) Kinetic Rationale for Cytokine-Induced Recruitment of Myeloblastic Leukaemia Followed by Cycle-Specific Chemotherapy In Vitro. Leukemia 4: No 12,826–834
Gandhi V, Estey E, Keating MJ, Plunkett W (1993) Fludarabine Potentiates Metabolism of Cytarabine in Patients With Acute Myelogenous Leukemia During Therapy. Journal of Clinical Oncology 11: No 1,116–124
Estey E, Thall P, Andreeff M, Beran M, Kantarjian H, O_Brien S, Escudier S, Robertson LE, Koller C, Kornblau S, Pierce S, Freireich EJ, Deisseroth A, Keating M (1994) Use of Granulocyte Colony-Stimulating Factor Before, During, and After Fludarabine Plus Cytarabine Induction Therapy of Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndromes: Comparison With Fludarabine Plus Cytarabine Without Granulocyte Colony-Stimulating Factor. Journal of Clinical Oncology 12: No 4,671–678
Visani G, Tosi P, Zinzani PL, Manfroi S, Ottaviani E, Testoni N, Clavio M, Cenacchi A, Gamberi B, Carrera P, Gobbi M, and Tura S (1994) FLAG (Fludarabine + High-Dose Cytarabine + G-CSF): An Effective and Tolerable Protocol for the Treatment of 4 Poor Risk_ Acute Myeloid Leukemias. Leukemia 8: No 11,1842–1846
Burnett AK, Goldstone AH, Stevens RMF, Hann IM, Rees JKH, Gray RG, Wheatley K (1998) Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet 351: 700–708
Huhmann IM, Watzke HH, Geissler K, Gisslinger J, Jäger U, Knöbl P, Pabinger I, Korninger L, Mannhalter C, Mitterbauer G, Schwarzinger I, Kalhs P, Haas OA, Lechner K (1996) FLAG (fludarabine, cytosine arabinoside, G-CSF) for refractory and relapsed acute myeloid leukemia. Ann Hematol 73:265–271
Nokes TJC, Johnson S, Harvey D, Goldstone AH (1997) FLAG is a Useful Regimen for Poor Prognosis Adult Myeloid Leukaemias and Myelodysplastic Syndromes. Leukemia and Lymphoma 27: 93–101
Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F (1998) Fludarabine, Cytarabine and G-CSF (FLAG) for the Treatment of Poor Risk Acute Myeloid Leukemia. American Journal of Haematology 58: 105–109
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Proctor, S. (2001). Multi Centre Study of a Combination of Fludarabine Phosphate, Cytosine Arabinoside and Granulocyte Colony Stimulating Factor (FLAG) in Relapsed and Refractory Acute Myeloid Leukaemia and in De Novo RAEB-t. In: Büchner, T., Hiddemann, W., Wörmann, B., Schellong, G., Ritter, J., Creutzig, U. (eds) Acute Leukemias VIII. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18156-6_34
Download citation
DOI: https://doi.org/10.1007/978-3-642-18156-6_34
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62109-3
Online ISBN: 978-3-642-18156-6
eBook Packages: Springer Book Archive