Abstract
There has been important progress in the treatment of Acute Myeloid Leukaemia (AML) in patients under 60 years. A remission rate of 80% can be achieved by several schedules, and 40–45% of patients diagnosed will survive. It may still be possible to improve remission induction treatment eg by intensifying the Ara-C dose although this may only be detectable in an improved disease free survival. The main challenge is to reduce relapse. The risk is pre-determined by a number of powerful risk factors. In the experience of the MRC age, cytogenetics and clearance of blasts from the bone marrow after course I. Using the later two in combination good risk patients (FAB M3, t(8;21) t(15;17) inv(16)) have a relapse risk of 32%. Poor risk (blasts >15% after course 1 or abnormalities of Chs 5 or 7, 3q- and complex changes have a relapse risk of 82%. All other cases are standard risk and have a relapse risk of 56%. FLT3 mutations have been detected in about 25% of cases and provide additional negative predictive value overall and within each risk group. The assessment of the most effective consolidation treatment must be made taking into account the heterogeneity of the relapse risk. The MRC investigated the role of allo and autoBMT in addition to intensive chemotherapy. The data was analysis on an intent-to-treat or donor vs no donor basis. Although both types of transplant were able to reduce relapse overall and in all risk groups, there was an overall survival advantage only in standard risk patients. Since chemotherapy has improved since this study, there remains uncertainty about the benefit of transplant in all risk groups. Overall this experience has demonstrated that relapse can be reduced with more therapy. It is probable that the limits of conventional chemotherapy have been reached. The new AML15 trial will assess the value of adding the immunoconjugate (Mylotarg) to induction and/or chemotherapy. Improvements in older patients have been less detectable. MRC trials over the last 20 years show an improvement in remission rate (now 65%) but persistent poor survival (12% at 5 years). In the MRC AML11 Trial three induction schedules were compared (DAT vs ADE vs MAC) with DAT being superior. A comparison of a total of 3 vs 6 courses of treatment or the addition of interferon maintenance did not improve results. Newer approaches currently being assessed include resistance modulation; addition of immunoconjugate and minigrafts. New targets for treatment are emerging of which the most interesting is FLT3 inhibitors.
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References
Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of acute leukaemia.Br J Haemotal. 1976;33:451.
Mertelsmann R, Thaler HT, Gee TS, et al. Morphological classification, response to therapy and survival in 263 adult patients with acute non-lymphoblastic leukaemia.Blood. 1980;56:773–81.
AK Burnett, AH Goldstone, RMF Stevens, et al. Randomised comparison of addition of autologous bone marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: AML 10 trial.Lancet. 1998;351:700–708.
Fenaux P, Morel P, Rose C, Lai JL, Jouet JP, Bauters F. Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy.Br J Haematol. 1991;77: 497–510.
Wood P, Burgess R, MacGregor A, Yiu Lin JA. P glyco-protein expression on acute myeloid leukaemic blast cells predicts response to chemotherapy and survival.Br J Haematol. 1994;87:509–514.
Zochbauer S, Gsur A, Brunner R, Kyrle PA, Lechner K, Pirker R. P-glycoprotein expression as unfavourable prognostic factor in acute myeloid leukaemia.Leukaemia. 1994;8:974–977.
Chessels JM, Bailey C, Richards SM, for the MRC Working Party on Childhood Leukaemia. Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of MRC trial UKALL X.Lancet. 1995;345:143–148.
LC Riley, IM Hann, K Wheatley, et al. Treatment-related deaths during induction and first remission of acute myeloid leukaemia in children treated on the Tenth Medical Research Council Acute Myeloid Leukaemia Trial (MRC AML10).Br J Haematol. 1999;106:436–444.
Preisler HD, Anderson K, Rai J, et al. The frequency of long term remission in patients with acute myeloid leukaemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimum follow up of six years.Br J Haematol. 1989;71:189–194.
Burnett AK, Wheatley K, Goldstone AH, et al. Attempts to improve induction treatment in AML patients under 60 years: The impact of mitoxantrone; ARA-C dose and retinoid acid: Results of MRC AML12.Haematol J. 2002;3(Suppl 1):159.
Vogler WR, Volaz-Gurcia E, Weiner RS, et al. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukaemia: a Southeastern Cancer Study Group study.J Clin Oncol. 1992;10:1103–1111.
Visani G, Tosi P, Zinzani PL, et al. FLAG (fludarabine plus high dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of poor risk myeloid leukaemias.Leukemia. 1994;8:1842–1846.
Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in adults with AML.N Engl J Med. 1994;331:896–903.
K Wheatley, AK Burnett, B Gibsox, et al. Optimising consolidation therapy: Four versus five courses SCT versus chemotherapy — Preliminary results of MRC AML12.Haematol J. 2002;3(Suppl 1):159.
Grignari F, Fagioli M, Alcalay M, et al. Acute promyelocytic leukemia: from genetics to treatment.Blood. 1994;83:10–25.
Fenaux P, Le Deleyu MC, Castaigne S, et al. Effect of alltrans retinoic acid in newly diagnosed acute promyelocytic leukaemia. Results of a multicentre randomised trial.Blood. 1993;11:3241–3249.
Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.J Clin Oncol. 2001;19:3852–3860.
Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and Safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.N Engl J Med. 2001;344:1031–1037
D Kottaridis, RE Gale ME Frew, et al. The Presence of a FLT3 Internal Tandem Duplication in patients with Acute Myeloid Leukemia (AML) adds important prognostic information to Cytogenetic Risk Group and Response to the First Cycle of Chemotherapy: Analysis of 854 Patients from the United Kingdom Medical Research Council AML 10 and 12 trials.Blood. 2001;98:1752–1759.
Russo D, De Angelo D, Castaigne S, et al. Report of the Safety and efficacy of gemtuxumab ozogamicin (Mylotarg) given in combination with cytarabine and daunorubicin in patients with acute myeloid leukemia: Phase 1.Haematol J. 2002;3(Suppl 1):159.
Horowitz MM, Gale RP, Sondel PM. Graft versus leukaemia reactions after bone marrow transplantation.Blood. 1990;65:555–562.
Zittoun RA, Mandelli F, Willemze R, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukaemia.N Engl J Med. 1995;332:217–223.
Brenner MK, Rill DR, Holladay MS, et al. Gene marking to determine whether autologous marrow infusion restores longterm haemopoiesis in cancer patients.Lancet. 1993;342:1134–1137.
McMillan AK, Goldstone AH, Linch DC, et al. High dose chemotherapy and autologous bone marrow transplantation in acute myeloid leukaemia.Blood. 1990;76:480–488.
Lim SH, Newland AC, Kelsey SM, et al. Continuous intravenous infusion of high dose recombinant interleukin 2 for acute myeloid leukaemia a phase II study.Cancer Immunol Immunother. 1992;34:337–342.
Williams MA, Kelsey SM, Collins PW, Gutteridge CN, Newland AC. Administration of GM-CSF activates monocyte reactive oxygen species secretion and adhesion molecule expression in vivo in patients following high dose chemotherapy.Br J Haematol. 1995;90:31–40.
Chajaraverty R, Peggs K, Chopra R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using nonmyeloablative conditioning regimenBlood. 2002;99:1071–1078.
Jiang XR, Macey MG, Collins PW, Newland AC. Characterisation and modulation of drug transport kinetics in K562 c16 daunorubicin-resistent cell line.Br J Haematol. 1994;86:547–554.
Gisselbrecht C, Prentice HG, Bacigalupo A, et al. Placebo controlled phase III trial of lenograstim in bone marrow transplantation.Lancet. 1994;343:696–699.
Stone RM, Berg DT, George SL, et al. GM-CSF after initial chemotherapy for elderly patients with acute myeloid leukaemia.N Engl J Med. 1995;332:1678–1683.
Dombret H, Chastang C, Fenaux P, et al. A controlled study of rhG-CSF in elderly patients after treatment for AML.N Engl J Med. 1995;332:1678–1683.
Juttner CA, To LB. Peripheral blood stem cells for therapeutic use. In: Burnnett A, Armitage J, Newland AC, Keating A, eds.Haematological Oncology 3. Cambridge, Cambridge University Press: 147–168.
Estey E, Thall PF, Kantarjian H,et al. Treatment of newly diagnosed acute myelogenous leukaemia with GM-CSF before and during continuous infusion with high dose ara-C and daunorubicin: comparison to patients treated without GM-CSFBlood. 1992;79:2246–2255.
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Newland, A. Progress in the treatment of acute myeloid leukaemia in adults. Int J Hematol 76 (Suppl 1), 253–258 (2002). https://doi.org/10.1007/BF03165254
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DOI: https://doi.org/10.1007/BF03165254