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Patients older than 80 years with de novo acute myeloid leukemias without erythroblastic and/or megakaryocytic dysplasia achieve complete remission and longer survival after classical chemotherapy 3 + 7


Authors: P. Lemež 1,4;  J. Gáliková 1;  K. Michalová 2;  D. Dvořáková 3;  A. Macwhannell 4;  Z. Zemanová 2;  J. Stejskal 3
Authors‘ workplace: Hematologicko‑transfuzní oddělení Nemocnice Jihlava, přednostka prim. MUDr. Jiřina Gáliková 1;  Centrum nádorové cytogenetiky Ústavu klinické bio­chemie 1. lékařské fakulty UK a VFN Praha, vedoucí prof. Ing. Kyra Michalová, DrSc. 3Oddělení klinické a radiační onkologie Krajské nemocnice Pardubice, přednosta doc. MUDr. Jaroslav Vaňásek, CSc. 2;  Department of Hematology, New Cross Hospital, Wolverhampton, England, vedoucí M. D. S. Basu, FRCPath. 4
Published in: Vnitř Lék 2010; 56(1): 37-43
Category: Original Contributions

Overview

Chemotherapy in most patients with AML over 80 years of age is not recommended because their median survival is about 1 month. The aim of our study was to identify patients in this age group who might achieve complete remission with standard dose chemotherapy. We report 9 consecutive patients with de novo AML diagnosed and treated in 1992–2008. All bone marrow samples were hypercellular, classified as FAB types M2 in 2 cases, M4 in 6, and M5 in one case. Three patients opted for supportive or palliative therapy and survived 1–4 months. Six patients received standard dose chemotherapy. Two patients with a normal karyotype had resistant AML and survived 1.0 and 2.7 months; one patient with a complex karyotype died of septic shock on the 10th day of therapy. All these three patients exhibited erythroblastic and/or megakaryocytic dysplasia (EMD) at presentation (two in more than 26% erythroblasts, all three in a half or more of megakaryocytes). Three remaining patients with AML M4, a normal karyotype but without EMD, achieved complete remission in spite of co-morbidities and a poor performance status. Two of them survived 18.6 and 28 months on maintenance therapy, the third 16.5 months without it. Very elderly AML patients without EMD appear to represent a favorable prognostic bio­logical category (single‑lineage AML) that show a good response to standard dose chemotherapy.

Key words:
acute myeloid leukemias – patients aged over 80 years – single‑lineage AMLs – multi‑lineage AMLs – normal karyotype – standard dose chemotherapy – dexrazoxane


Sources

1. Peterson BA, Bloomfield CD. Treatment of acute nonlymphocytic leukemia in elderly patients. Cancer 1977; 40: 647–652.

2. Copplestone JA, Smith AG, Osmond C et al. Treatment of acute myeloid leukemia in the elderly: a clinical dilemma. Hematol Oncol 1989; 7: 53–59.

3. Hamblin T. Treatment of acute myeloid leukaemia preceded by the myelodysplastic syndrome. Leukemia Res 1992; 16: 101–108.

4. De Lima M, Ghaddar H., Pierce S et al. Treatment of newly-diagnosed acute myelogenous leukaemia in patients aged 80 years and above. Br J Haematol 1996; 93: 89–95.

5. Ferrara F, Annunziata M, Copia C et al. Therapeutic options and treatment results for patients over 75 years of age with acute myeloid leukemia. Haematologica 1998; 83: 126–131.

6. Löwenberg B, Suciu S, Archimbaud E et al. Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy – the value of low‑dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report of the Leukemia Cooperative Group of the European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group randomized phase III study AML‑9. J Clin Oncol 1998; 16: 872–881.

7. Büchner T, Berdel WE, Wörmann B et al. Treatment of older patients with AML. Crit Rev Oncol Hematol 2005; 56: 247–259.

8. Appelbaum FR, Gundacker H, Head DR et al. Age and acute myeloid leukemia. Blood 2006; 107: 3481–3485.

9. Harris NL, Stein H, Vardiman JW (eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissue. Lyon, France: IARC Press, 2001.

10. Bennett JM, Catovsky D, Daniel MT et al. Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 1985; 103: 620–625.

11. Lemež P. Significance of lineage specific differentiation markers for complex classification of acute leukemias. Neoplasma 1990; 37: 253–281.

12. Lemež P, Jelínek J, Michalová K et al. Near‑tetraploid poorly differentiated acute myeloid leukemia M0 diagnosed by short‑term cultures with a phorbol ester TPA. Leukemia Res 1994; 18: 493–497.

13. Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of myelodysplastic syndromes. Br J Haematol 1982; 51:189–199.

14. Lemež P, Gáliková J, Haas T. Erythroblastic and/or megakaryocytic dysplasia in de novo acute myeloid leukemias M0-M5 show relation to myelodysplastic syndromes and delimit two main categories. Leukemia Res 2000; 24: 207–215.

15. Lemež P, Gáliková J, Haas T. Do de novo acute myeloid leukemias with normal cytogenetics involve two main prognostic categories distinguished by the presence of erythroblastic and/or megakaryocytic dysplasia? Neoplasma 2000; 47: 41–47.

16. Mitelman F (ed). ISCN: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S. Karger 1995.

17. Babická L, Ransdorfová S, Březinová J et al. Analysis of complex chromosomal rearrangements in adult patients with MDS and AML by multicolor FISH. Leukemia Res 2007; 31: 39–47.

18. Lemež P, Marešová J. Protective effects of cardioxane against anthracycline‑induced cardiotoxicity in relapsed acute myeloid leukemias. Neoplasma 1996; 43: 417–419.

19. Cheson BD, Cassileth PA, Head DR et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 1990; 8: 813–819.

20. Jinnai I, Tomonaga M, Kuriyama K et al. Dysmegakaryocytopoiesis in acute leukaemias: its predominance in myelomonocytic (M4) leukaemia and implication for poor response to chemotherapy. Br J Haematol 1987; 66: 467–472.

21. Delacrétaz F, Spertini O, Schmidt PM et al. Dysmegakaryopoiesis predicting response to therapy in acute myeloid leukaemia. Path Res Pract 1991; 187: 290–295.

22. Brito‑Babapulle F, Catovsky D, Galton DAG Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia. Br J Haematol 1987; 66: 445–450.

23. Estienne MH, Fenaux P, Preudhomme Cet al. Prognostic value of dysmyelopoietic features in de novo acute myeloid leukaemia: a report on 132 patients. Clin Lab Haematol 1990; 12: 57–65.

24. Goasguen JE, Matsuo T, Cox C et al. Evaluation of the dysmyelopoiesis in 336 patients with de novo acute myeloid leukemia: importance of dysgranulopoiesis for remission and survival. Leukemia 1992; 6: 520–525.

25. Lemež P, Vítek A, Michalová K et al. Dlouhodobé výsledky léčby dospělých nemocných do 65 let s de novo akutními myeloidními leukemiemi bez příznivých karyotypů ve studii ÚHKT‑911. Vnitř Lék 2003; 49: 174–180.

26. Fernández-Ferrero S, Ramos F. Dyshaemopoietic bone marrow features in healthy subjects are related to age. Leukemia Res 2001; 25:187–189.

27. Venditti A, Del Poeta G, Buccisano F et al. Minimally differentiated acute myeloid leukemia (AML M0): comparison of 25 cases with other French-American-British subtypes. Blood 1997; 89: 621–629.

28. Mason KD, Juneja SK, Szer J. The immunophenotype of acute myeloid leukemia: is there a relationship with prognosis? Blood Review 2006; 20: 71–82.

29. Doubek M, Palasek I, Brychtová Y et al. Acute myeloid leukemia treatment in patients over 60 years of age. Comparison of symptomatic, palliative, and agressive therapy. Neoplasma 2005; 52: 411–415.

30. Woodlock TJ, Lifton R, DiSalle M. Coincident acute myelogenous leukemia and ischemic heart disease: use of the cardioprotectant dexrazoxane during induction chemotherapy. Am J Hematol 1998; 59: 246–248.

31. Lemež P, Stejskal J, Cahová S et al. Dexrazoxan u nemocných s B‑lymfomy nebo akutními leukemiemi ve 2. kompletní remisi umožňuje další léčbu kardiotoxickými antracykliny nad doporučené kumulativní dávky. Vnitř Lék 2004; 50: 438–446.

32. Cvetkovic RS, Scott LJ. Dexrazoxane: a review of its use for cardioprotection during anthracycline chemotherapy. Drugs 2005; 65: 1005–1024.

33. Arthur DC, Berger R, Golomb HM et al. The clinical significance of karyotype in acute myelogenous leukemia. Cancer Genet Cytogenet 1989; 40: 203–216.

34. Golub TR, Slonim DK, Tamayo P et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999; 286: 531–537.

35. Mrózek K, Marcucci G, Paschka P et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 2007; 109: 431–448.

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