The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia


1 Department of internal medicine, Alzahra Hospital, Isfahan, Iran

2 Health department, Isfahan Universityy of medical sciences, Isfahan, Iran


Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen.
Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19.
Results: Out of the 25 patients, 8 patients (32%) had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases) and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases). According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40%) had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT). On the other hand, 13 patients (52%), who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment.
Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure) in Iran, it seems that FLANG therapy is an acceptable choice for these patients.


1. Greinix HT, Reiter E, Keil F, Fischer G, Lechner K, Dieckmann K, et al. Leukemia-free survival and mortality in patients with refractory or relapsed acute leukemia given marrow transplants from sibling and unrelated donors. Bone Marrow Transplant 1998;21:673-8.  Back to cited text no. 1
2. Kell J. Treatment of relapsed acute myeloid leukaemia. Rev Recent Clin Trials 2006;1:103-11.  Back to cited text no. 2
3. Löwenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999;341:1051-62.  Back to cited text no. 3
4. Craddock C, Tauro S, Moss P, Grimwade D. Biology and management of relapsed acute myeloid leukaemia. Br J Haematol 2005;129:18-34.  Back to cited text no. 4
5. Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2004;98-117.  Back to cited text no. 5
6. Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. Treatment of adult acute lymphoblastic leukemia (ALL): Long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 2002;99:863-71.  Back to cited text no. 6
7. Oriol A, Vives S, Hernández-Rivas JM, Tormo M, Heras I, Rivas C, et al. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica 2010;95:589-96.  Back to cited text no. 7
8. Martin MG, Augustin KM, Uy GL, Welch JS, Hladnik L, Goyal S, et al. Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF. Am J Hematol 2009;84:733-7.  Back to cited text no. 8
9. Steinmetz HT, Schulz A, Staib P, Scheid C, Glasmacher A, Neufang A, et al. Phase-II trial of idarubicin, fludarabine, cytosine arabinoside, and filgrastim (Ida-FLAG) for treatment of refractory, relapsed, and secondary AML. Ann Hematol 1999;78:418-25.  Back to cited text no. 9
10. 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 myelodysplastic syndromes: Comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol 1994;12:671-8.  Back to cited text no. 10
11. 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 blasts in transformation. Br J Haematol 2001;112:127-37.  Back to cited text no. 11
12. Mohagheghi M, Alireza Mosavi-Jarrahi. Cancer registry, Final Report. 2002. The Cancer Institute Research Center.  Back to cited text no. 12
13. Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: Single-center experience. Ann Hematol 2003;82:231-5.  Back to cited text no. 13
14. Martinez JA, Martin 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;9:39-43.  Back to cited text no. 14
15. Larrea L, Martínez JA, Sanz GF, Martín G, de la Rubia J, Jimenez C, et al. Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia. Leukemia 1999;13:161-5.  Back to cited text no. 15
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;8:1842-6.  Back to cited text no. 16
17. Suki S, Kantarjian H, Gandhi V, Estey E, O'Brien S, Beran M, et al. Fludarabine and cytosine arabinoside in the treatment of refractory or relapsed acute lymphocytic leukemia. Cancer 1993;72:2155-60.  Back to cited text no. 17
18. 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;102:647-55.  Back to cited text no. 18
19. Hashmi KU, Khan B, Ahmed P, Raza S, Hussain I, Mahmood A, et al. FLAG-IDA in the treatment of refractory/relapsed acute leukaemias: Single centre study. J Pak Med Assoc 2005;55:234-8.  Back to cited text no. 19
20. Yalman N, Sarper N, Devecioðlu O, Anak S, Eryilmaz E, Can M, et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of relapsed or poor risk childhood acute leukemia. Turk J Pediatr 2000;42:198-204.  Back to cited text no. 20
21. Dominguez Senín L, Rodríguez Rodríguez JN, Garrido Martínez MT, Sánchez Argáiz M, Martín Chacón E. Effectiveness and safety of the FLAG-IDA regimen in acute refractory or recurrent leukaemia. Farm Hosp 2011; Dec 1.  Back to cited text no. 21
22. Tavil B, Aytac S, Balci YI, Unal S, Kuskonmaz B, Yetgin S, et al. Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) for the treatment of children with poor-prognosis acute leukemia: The Hacettepe experience. Pediatr Hematol Oncol 2010;27:517-28.  Back to cited text no. 22
23. Virchis A, Koh M, Rankin P, Mehta A, Potter M, Hoffbrand AV, et al. Fludarabine, cytosine arabinoside, granulocyte-colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes. Br J Haematol 2004;124:26-32.  Back to cited text no. 23
24. Lamba JK. Genetic factors influencing cytarabine therapy. Pharmacogenomics 2009;10:1657-74.  Back to cited text no. 24
25. Jamali J, Feizi A, Hosseini SM, Kazemnejad A, Parsayekta Z. Knowledge level of the warning signs of cancer and its affecting factors in Tehran's population above 18 years. J Birjand Univ Med Sci 2011;17:296-307.  Back to cited text no. 25