Comorbidities and FLT3 Abnormalities as Independent Prognostic Indicators of Survival in Elderly Acute Myeloid Leukemia Patients

Abstract

Elderly AML patients have a dismal prognosis due to biological features of disease in itself and to presence of comorbidities. Aim of present study was to evaluate the prognostic impact of comorbidity prognostic score systems applied in our population of patients, as well as of other clinical-biological features. We retrospectively considered the outcome of 120 patients aged > 65 years diagnosed as having AML between January 2001 and December 2005. Comorbidities were investigated retrospectively and 3 scores were applied to the whole patient population: the modified Charlson comorbidity index (CCI), the Hematopoietic cell transplantation-comorbidity index (HCTCI) and the score proposed by Dombret et al at ASH 2006, which considered as prognostic parameters documented infections at presentation, presence of chronic pulmonary diseases, PS >1 and high risk cytogenetic category. For all patients clinical and biological features at presentation (age, sex, WHO performance status, prior hematological disorder, presence of fever and/or documented infection, percentage of BM and PB blast cells, blood cell counts, hemoglobin level, coagulation tests) were analysed as well as survival with respect to the presence or not of FLT3 abnormalities. Median age of whole population was 62 years. Sixty-eight patients (57%) were aged >70 years. Thirty-five patients (29%) had an antecedent myelodysplastic phase. Cytogenetic analysis showed high frequency of intermediate/high risk karyotype and immunophenotype showed 62 patients (52%) to be positive for CD34 expression. Renal impairment was evident at diagnosis in 11 patients. Molecular analysis showed FLT3 as unique abnormality in 11 patients (9%). Comorbidity conditions at diagnosis included cardiac dysfunction in 46 patients, diabetes in 10 patients, other neoplasias in 3 patients, pulmonary disease in 18 patients, renal impairment in 7 patients and infections documented at diagnosis in 16 patients. Score was low (0–1) in 70% of patients by CCI, in 40% by HCT-CI and in 80% by Dombret et al criteria. In univariate analysis we tested presenting features which were associated with worse outcome. We found a significant association between a shorter survival and leukocytosis > 100 × 109/l (p=0.005), antecedent myelodysplastic phase (p=0.04), high-risk karyotype (p=0.05), FLT3 abnormalities (p=0.03), fever at presentation (p=0.023), CCI stratification (p=0.027) and Dombret et al stratification (p=0.045). Age, sex, performance status, and presence of CD34 antigen positivity were not independent prognostic parameters. In the multivariate analysis leukocytosis (p=0.0013), antecedent MDS (p=0.011), FLT3 abnormalities (p=0.032), CCI (p=0.0037) and Dombret et al score (p=0.045) were confirmed as independent prognostic parameters for survival. Based on results of multivariate analysis for survival we stratified elderly patients into two risk groups according to the presence or not of the following risk factors: leukocytosis, antecedent MDS phase, FLT3 abnormalities, CCI or Dombret et al score > 2. Patients were considered as low risk if they had none or only one of the above mentioned adverse factors for survival: these patients had a median OS of 447 days. Patients with two or more adverse factors were categorized as high risk: this subgroup had a median OS of 227 days (p=0.001). In conclusion, comorbidities are independent factors that influence survival. Application of CCI and Dombret score may help to better identify patients at diagnosis who can benefit from intensive chemotherapy.