Prognostic factors in elderly patients with acute myeloid leukemia
Abstract
Background: Acute myeloid leukemia (AML) is characterized by pathological proliferation of myeloid lineages. It predominantly occurs in patients over 60 years of age, whose outcome is considerably worse comparing to younger patients.
Aim: Analysis of clinical characteristics of older patients with AML and their impact on achieving complete remission (CR), overall survival (OS), early mortality (EM) and relapse.
Materials and methods: The study included 94 patients with AML, treated with chemotherapy and palliative therapy, whose informations were taken from their medical history. The following clinical features were studied as risk factors for OS, KR, relapse and EM: leukocytes, serum lactate dehydrogenase (LDH), ECOG (Eastern Cooperative Oncology Group), European LeukemiaNet cytoplasmic risk group, HCT-CI (hematopoetic cell transplantation- comorbidity index) and NPM1/FLT3-ITD (Nukleofosmin/FLT3-internal tandem mutation) molecular status. For the identification of prognostic factors, a Cox regression analysis was used.
Results: The average age of patients was 69 years (range: 65-87). CR was achieved in 23 (24.5%) patients of 50 (53.2%) who received intensive chemotherapy, with relapse occurring in 17 (70.8%). EM was reported in 17 (18.1%) patients. Patients with ECOG PS > 2 had statistically significant lower OS than patients with ECOG PS < 2 (p = 0.030). Patients with HCT-CI > 3 had a poorer OS than patients with HCT-CI < 3 (p = 0.040). Serum LDH > 450 U/I was found to be a poor prognostic factor for the OS compared to LDH < 450U/I (p = 0.044).
Conclusion: Older AML patients with poorer ECOG PS, high HCT-CI, increased LDH levels have a poorer OS.
References
2. Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2005. SEER Database, National Cancer Institute; 2009.
3. Hiddeman W, Kern W, Schoch C, et al. Management of acute myeloid leukemia in elderly patients. J Clin Oncol.1999;17:3569–76.
4. Stone RM. The difficult problem of acute myeloid leukemia in older adult. CA Cancer J Clin. 2002;52:363–71.
5. Appelbaum FR, Gundacker H, Head DR, Slovak, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–5.
6. Kantarjian H, O’Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high risk myelodisplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090-8.
7. Djunic I, Virijevic M, Novkovic A, et al. Comorbidity as a risk factor for overall survival and decision criteria for intensity of chemotherapy in elderly patients with acute myeloid leukemia. Med Oncol. 2012;29:1077–81.
8. Pulsoni A, Pagano L, Latagliata R, et al. Survival of elderly patients with acute myeloid leukemia. Haematologica. 2004;89:296-302.
9. Röllig C, Thiede C, Gramatzki M, et al. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood.2010;116(6):971-8.
10. Malfuson JV, Etienne A, Turlure P, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica.2008;93:1806–13.
11. Erba HP. Prognostic factors in elderly patients with AML and the implications for treatment. Hematology Am Soc Hematol Educ Program.2007:420-8.
12. Wedding U, Höffken K. Therapy of acute myeloid leukemia in the elderly patient. Z Gerontol Geriatr.2001;34(4):269-76.
13. Oken MM, Creech RH, Tormey DC,et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J ClinOncol1982;5:649-55.
14. Sorror ML, Storb RF, Sandmaier BM, et al. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J ClinOncol 2014; 32: 3249- 56.
15. Döhner H, Estey EH, Amadori S, et al..Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net. Blood2010;115:453-74.
16. Arber DA, Brunning RD, Le Beau, et al. MM WHO classification. IARC. Lyon, 2008;p.110-146.
17. Bene MC, Nebe T, Bettelheim P, et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia.2011;25(4):567-74.
18. International System for Human Cytogenetic Nomenclature (ISCN). Recomendations for the International Standing Commitee on Human Cytogenetic Nomenclature. Memphis, Thenessy, USA,1994.
19. Cheson BD, Bennet JM, Kopecky KJ, et al. International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcome, and reporting standards for therapeutic trials in acute myeloid leukemia. J ClinOncol2003;21:4642–9.
20. Walter RB, Othus M, Borthakur G, et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J ClinOncol. 2011; 29(33):4417-23.
21. Breccia M, Frustaci AM, Cannella L, et al. Comorbidities and FLT3-ITD abnormalities as independent prognostic indicators of survival in elderly acute myeloid leukemia patients. Haem Oncol.2009;27:148–53.
22. Fröhling S, Schlenk RF, Kayser S, et al. for the German-Austrian AML StudyGroup. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood.2006;108:3280-8.
23. AppelbaumFR,GundackerH,HeadDR.,etal.Age and acute myeloid leukemia. Blood. 2006;107:3481-5.
24. Menzin J, Lang K, Earle CC, Kerney D, Mallick R., The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med.2002;162:1597-1603.
25. Etienne A, Esterni B, Charbonnier A, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer.2007;109:1376–83.
26. Giles FJ, Borthakur G, Ravandi F, et al. The haematopoetic cell transplantation comorbidity index score predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukemia. Br J Haematol.2007;136:624–7.